March 2016 cancer current awareness2 by Musgrove Park Hospital Library

Clinical Librarian Service Musgrove Park Academy

Current Awareness

Cancer Issue 4 March 2016

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This monthly Current Awareness Bulletin is produced by the Clinical Librarian, Musgrove Park Academy, to provide Hope Directorate staff with a range of cancer/haematology related resources to support practice. It includes recently published guidelines and research articles, news and policy items.

This guide provides a selection of resources relevant to the subject area and is not intended to be a comprehensive list. For further help or guidance, please contact a member of library staff.

This guide has been compiled by: Terry Harrison MLGS Clinical Librarian, HOPE Directorate Musgrove Park Hospital Library Service Terence.Harrison@tst.nhs.uk

Contents Click on a section title to navigate to contents

Page Recent journal articles

New books

Cochrane Reviews

Other evidence updates

Cancer in the News

Reports, publications and resources

Training & Networking Opportunities, Conferences, Events

Literature & Evidence search services

Training and Athens

Library contact details: Library Musgrove Park Academy Musgrove Park Hospital Taunton Somerset TA1 5DA Email: Library@tst.nhs.uk Tel: 01823 34 (2433) Fax: 01823 34 (2434) Clinical Librarian email: Terence.Harrison@tst.nhs.uk

RECENT JOURNAL ARTICLES BACK TO TOP

This is a list of recent journal articles on the topic of cancer (and haematology). Some articles are available in the library, or on-line via an Athens password, by following the link. If you would like an article that is not available as full text, please contact library staff: Library@tst.nhs.uk

Exploiting evolutionary principles to prolong tumor control in preclinical models of breast cancer Pedro M. Enriquez-Navas, Yoonseok Kam, Tuhin Das, et al Science Translational Medicine 24 Feb 2016: Vol. 8, Issue 327, pp. 327ra24 Conventional cancer treatment strategies assume that maximum patient benefit is achieved through maximum killing of tumor cells. However, by eliminating the therapy-sensitive population, this strategy accelerates emergence of resistant clones that proliferate unopposed by competitors—an evolutionary phenomenon termed “competitive release.” We present an evolution-guided treatment strategy designed to maintain a stable population of chemosensitive cells that limit proliferation of resistant clones by exploiting the fitness cost of the resistant phenotype. We treated MDA-MB-231/luc triple-negative and MCF7 estrogen receptor–positive (ER+) breast cancers growing orthotopically in a mouse mammary fat pad with paclitaxel, using algorithms linked to tumor response monitored by magnetic resonance imaging. We found that initial control required more intensive therapy with regular application of drug to deflect the exponential tumor growth curve onto a plateau. Dose-skipping algorithms during this phase were less successful than variable dosing algorithms. However, once initial tumor control was achieved, it was maintained with progressively smaller drug doses. In 60 to 80% of animals, continued decline in tumor size permitted intervals as long as several weeks in which no treatment was necessary. Magnetic resonance images and histological analysis of tumors controlled by adaptive therapy demonstrated increased vascular density and less necrosis, suggesting that vascular normalization resulting from enforced stabilization of tumor volume may contribute to ongoing tumor control with lower drug doses. Our study demonstrates that an evolution-based therapeutic strategy using an available chemotherapeutic drug and conventional clinical imaging can prolong the progression-free survival in different preclinical models of breast cancer.

A phase I study of MK-5108, an oral aurora a kinase inhibitor, administered both as monotherapy and in combination with docetaxel, in patients with advanced or refractory solid tumors Amin, Manik; Minton, Susan E; Lorusso, Patricia M; et al MK-5108 is a potent/highly selective Aurora A kinase inhibitor. A randomized Phase I study of MK5108, administered p.o. BID Q12h on days 1-2 in 14-21 day cycles either alone (MT; Panel1/n=18; 200 to 1800 mg) or in combination (CT; Panel2/n=17; 100 to 225 mg) with IV docetaxel 60 3

mg/m^sup 2^, determined the maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics (Panel1, only) and tumor response in patients with advanced solid tumors. This study was terminated early due to toxicities in Panel2 at MK-5108 doses below the anticipated PK exposure target. Thirty-five patients enrolled (33 evaluable for tumor response). No dose-limiting toxicities (DLTs) were observed in Panel1; three patients had 3 DLTs in Panel2 (G3 and G4 febrile neutropenia at 200 and 450 mg/day, respectively; G3 infection at 450 mg/day). In Panel1, AUC^sub 0-12hr^ and C^sub max^ increased less than dose proportionally following the first MT dose but increased roughly dose proportionally across 200 to 3600 mg/day after 4th dose. The t^sub 1/2^ ranged from 6.6 to 13.5 h across both panels. No clear effects on immunohistochemistry markers were observed; however, significant dose-related increases in gene expression were seen pre-/posttreatment. Best responses were 9/17 stable disease (SD) (Panel1) as well as 1/16 PR and 7/16 SD (Panel2) (450 mg/day). MK-5108 MT was well tolerated at doses up to 3600 mg/day with plasma levels exceeding the minimum daily exposure target (83 [mu]M*hr). The MTD for MK-5108 + docetaxel (CT) was established at 300 mg/day, below the exposure target. Use of pharmacodynamic gene expression assays to determine target engagement was validated.

Anti-tumoral effect of arsenic compound, sodium metaarsenite (KML001), in non-Hodgkin's lymphoma: an in vitro and in vivo study Yoon, Jin Sun; Hwang, Deok Won; Kim, Eun Shil; Kim, Jung Soon; Kim, Sujong; et al. Investigational New Drugs34.1 (Feb 2016): 1-14. Arsenic compounds have been used in traditional medicine for several centuries. KML001 (sodium metaarsenite; NaAsO2) is an orally bio-available arsenic compound with potential anti-cancer activity. However, the effect of KML001 has not been studied in lymphoid neoplasms. The aim of this study is to evaluate the anti-proliferative effect of KML001 in non-Hodgkin's lymphoma and to compare its efficacy with As^sub 2^O3. KML001 inhibited cellular proliferation in all tested lymphoma cell lines as well as JurkatR cells (adriamycin-resistant Jurkat cells) in a dose-dependent manner, while As^sub 2^O3 was not effective. Cell cycle regulatory protein studies have suggested that KML001 induces G1 arrest via p27-induced inhibition of the kinase activities of CDK2, 4, and 6. Treatment of KML001 induced apoptosis in Jurkat and JurkatR cells. The apoptotic process was associated with down-regulation of Bcl-2 (antiapoptotic molecule), up-regulation of Bax (proapoptotic molecule), and inhibition of caspase-3, -8, and -9. In addition, cell signaling including the STAT, PI3K/Akt, MAPK, and NF-[kappa]B signal pathways were inhibited in KML001-treated Jurkat and JurkatR cells. Furthermore, targeting the telomere by KML001 was observed in the Jurkat and JurkatR cells. The In vivo anti-tumoral activity of KML001 was confirmed in a xenograft murine model. Interestingly, partial responses were seen in two lymphoma patients treated with 10 mg/day (follicular lymphoma for 16 weeks and mantle cell lymphoma for 24 weeks) without severe toxicities. These findings suggest that KML001 may be a candidate agent for the treatment of de novo, refractory, and relapsed non-Hodgkin's lymphoma patients.

Phase I, dose-escalating study of elisidepsin (Irvalec^sup ^), a plasma membrane-disrupting marine antitumor agent, in combination with erlotinib in patients with advanced malignant solid tumors Goel, Sanjay; Viteri, Santiago; MorĂĄn, Teresa; et al Investigational New Drugs, February 2016, Volume 34, Issue 1, pp 75-83 The objective of this paper is to determine the recommended dose for phase II trials of elisidepsin (PM02734, Irvalec) in combination with erlotinib in patients with advanced malignant solid tumors. Open-label, dose-escalating, phase I study of intravenous elisidepsin administered weekly (days 1, 8 and 15) over 3 h as a flat dose (FD) and daily oral erlotinib, every 3 weeks. A pharmacokinetic analysis was done on blood samples collected around the first elisidepsin infusion. Results Thirty patients were treated across six different dose levels (DLs) ranging from elisidepsin 0.33-2.25 mg/erlotinib 100-150 mg. Two patients had dose-limiting toxicities: grade 3 bilirubin increase (DL3: 0.75 mg/150 mg) and a dose omission for>2 weeks due to grade 3 alanine aminotransferase increase (DL6: 2.25 mg/100 mg). The daily erlotinib dose was escalated to 150 mg at DL2-DL5, but decreased to 100 mg at DL6, as most grade 3 toxicities were related to this agent only. The most frequent toxicities were transaminase increases (related to elisidepsin), and rash, pruritus and diarrhea (related to erlotinib). No objective responses were observed. Despite no overlapping toxicities, the combination was declared unfeasible due to frequent elisidepsin dose delays. The pharmacokinetics of elisidepsin/erlotinib was not significantly different from that of each agent alone. The difficulty in combining elisidepsin with the standard dose of erlotinib (150 mg), together with the lack of antitumor activity, made the combination unattractive for further development. The trial was closed without having determined a recommended dose.

Relationship between obesity and clinical outcome in adults with acute myeloid leukemia: A pooled analysis from four CALGB (alliance) clinical trials Castillo, Jorge J; Mulkey, Flora; Geyer, Susan; Kolitz, Jonathan E; Blum, William; et al. American Journal of Hematology91.2 (Feb 2016): 199-204. Obesity has been previously suggested as an adverse prognostic marker in patients with acute leukemia. To evaluate the relationship between obesity and clinical outcome, disease-free survival (DFS) and overall survival (OS), in patients with acute myelogenous leukemia (AML), including acute promyelocytic leukemia (APL), we performed a pooled analysis of four CALGB (Alliance) clinical trials. Our study included 446 patients with APL from CALGB 9710, and 1,648 patients between 18 and 60 years of age with non-APL AML from CALGB 9621, 10503, and 19808. Obesity was defined as BMI â&#x2030;Ľ 30 kg/m2. Multivariate Cox proportional-hazard regression models were fitted for DFS and OS. Obesity was seen in 50% and 38% of APL and non-APL AML patients, respectively. In APL patients, obesity was associated with worse DFS (HR 1.53, 95% CI 1.03-2.27; P = 0.04) and OS (HR 1.72, 95% CI 1.15-2.58; P = 0.01) after adjusting for age, sex, performance status, race, ethnicity, treatment arm and baseline white blood cell count. Obesity was not significantly associated with DFS or OS in the non-APL AML patients. In conclusion, our study indicates that obesity has significant prognostic 5

value for DFS and OS in APL patients, but not for non-APL AML patients. Am. J. Hematol. 91:199-204, 2016. ÂŠ 2015 Wiley Periodicals, Inc.

Design of chimeric antigen receptors with integrated controllable transient functions Alexandre Juillerat, Alan Marechal, Jean-Marie Filhol et al Scientific Reports 6, Article number: 18950 (2016) The ability to control T cells engineered to permanently express chimeric antigen receptors (CARs) is a key feature to improve safety. Here, we describe the development of a new CAR architecture with an integrated switch-on system that permits to control the CAR T-cell function. This system offers the advantage of a transient CAR T-cell for safety while letting open the possibility of multiple cytotoxicity cycles using a small molecule drug.

Therapeutic Potential of T Cell Chimeric Antigen Receptors (CARs) in Cancer Treatment: Counteracting Off-Tumor Toxicities for Safe CAR T Cell Therapy Annual Review of Pharmacology and Toxicology Vol. 56: 59-83 (Volume publication date January 2016) A chimeric antigen receptor (CAR) is a recombinant fusion protein combining an antibody-derived targeting fragment with signaling domains capable of activating T cells. Recent early-phase clinical trials have demonstrated the remarkable ability of CAR-modified T cells to eliminate B cell malignancies. This review describes the choice of target antigens and CAR manipulations to maximize antitumor specificity. Benefits and current limitations of CAR-modified T cells are discussed, with a special focus on the distribution of tumor antigens on normal tissues and the risk of on-target, off-tumor toxicities in the clinical setting. We present current methodologies for preevaluating these risks and review the strategies for counteracting potential off-tumor effects. Successful implementation of these approaches will improve the safety and efficacy of CAR T cell therapy and extend the range of cancer patients who may be treated

Community-acquired bacterial meningitis in adults with cancer or a history of cancer Joost M. Costerus, Matthijs C. Brouwer, Arie van der Ende, Diederik van de Beek Neurology 2016 Jan 22 One of 8 patients with community-bacterial meningitis was identified to have a history of cancer and cancer was considered active in half of these patients. Patients with active cancer present with lower CSF leukocyte counts, are more likely to be infected with L monocytogenes, and are at high risk of unfavorable outcome. 6

A. Miscellaneous Gastrectomy Plus Chemotherapy vs Chemotherapy Alone for Advanced Gastric Cancer With a Single Non-Curable Factor Lancet Oncol · February 04, 2016 Afatinib Plus Vinorelbine vs Trastuzumab Plus Vinorelbine in Patients With HER2-Overexpressing Metastatic Breast Cancer Who Had Progressed on One Previous Trastuzumab Treatment Lancet Oncol · February 04, 2016 Enzalutamide vs Bicalutamide in Castration-Resistant Prostate Cancer J. Clin. Oncol · February 04, 2016 Survival and Response in BRAF V600–Mutant Metastatic Melanoma Treated With Dabrafenib Combined With Trametinib J. Clin. Oncol · February 03, 2016 Gemtuzumab Ozogamicin vs Best Supportive Care in Older Patients With Newly Diagnosed AML J. Clin. Oncol · February 03, 2016 Serum HER2 Extracellular Domain as a Biomarker for Lapatinib Response in Advanced Breast Cancer J. Clin. Oncol · February 03, 2016 SLNB Status and Adjuvant Radiation Therapy in Merkel Cell Carcinoma Ann. Oncol · February 03, 2016 Efficacy and Safety of Enzalutamide vs Bicalutamide for Patients With Metastatic Prostate Cancer Lancet Oncol · February 03, 2016 Clinical Outcomes of Melanoma Brain Metastases Treated With Stereotactic Radiation and Anti-PD-1 Therapy Ann. Oncol · February 03, 2016 Nab-Paclitaxel vs Solvent-Based Paclitaxel in Neoadjuvant Chemotherapy for Early Breast Cancer Lancet Oncol; 2016 Feb 8; EPub Ahead of Print; M Untch, C Jackisch, A Schneeweiss, et al Epoetin Alfa vs Standard of Care in Anemic Women With Metastatic Breast Cancer Receiving Chemotherapy J. Clin. Oncol; 2016 Feb 8; EPub Ahead of Print; B Leyland-Jones, I Bondarenko, G Nemsadze, et al Minimally Invasive Hysterectomy in Women With Endometrial Cancer Is Safe, Effective J. Clin. Oncol; 2016 Feb 1; EPub Ahead of Print; JD Wright, WM Burke, AI Tergas, et al

B. More articles (via BMJ): 7

(IMPORTANT: you will need to logon to the BMJ to see the following items, or you can order items from the Library.) Breast cancer Chemotherapy could make breast cancer patients more vulnerable to common infections Jacqui Wise Statistics Notes: Inverse probability weighting Mohammad Ali Mansournia, Douglas G Altman Charity calls for routine BRCA testing of ovarian cancer patients Jacqui Wise Short intensive radiation courses may work as well as standard ones David Spurgeon Chemotherapy French drug trial had three major failings, says initial report Nigel Hawkes MPs find no evidence that Cancer Drugs Fund was spent wisely Nigel Hawkes Practice pointer: Treating hypertension in patients with medical comorbidities Lucinda Kennard, Kevin M Oâ&#x20AC;&#x2122;Shaughnessy CNS cancer Case Review: Headaches and hormones: a potentially lethal combination Ramdeep Bajwa, Paven Preet Kaur, Alessandro Paluzzi Colon cancer One in seven colorectal cancer patients is under 50, US study shows Jacqui Wise Facial surgeons call for review of two week cancer referral system Jacqui Wise

Cancer: dermatological Rheumatoid arthritis, TNF inhibitors, and non-melanoma skin cancer Shervin Assassi Rheumatoid arthritis, anti-tumour necrosis factor treatment, and risk of squamous cell and basal cell skin cancer: cohort study based on nationwide prospectively recorded data from Sweden Pauline Raaschou, Julia F Simard, Charlotte Asker Hagelberg, Johan Askling, for the ARTIS Study Group Sun exposure guidance should be tailored to individuals, says NICE Jacqui Wise Endocrine cancer Case Review: Headaches and hormones: a potentially lethal combination Ramdeep Bajwa, Paven Preet Kaur, Alessandro Paluzzi Gynecological cancer Charity calls for routine BRCA testing of ovarian cancer patients Jacqui Wise Atypical glandular cells on cervical cytology Marie-Hélène Mayrand, Anita Koushik Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide cohort study Jiangrong Wang, Bengt Andrae, Karin Sundström, Peter Ström, Alexander Ploner, K Miriam Elfström, Lisen Arnheim-Dahlström, Joakim Dillner, Pär Sparén Head and neck cancer Review rates of pathology findings for head and neck cancer vary hugely between hospitals, report finds Nigel Hawkes Hepatic cancer Decompensated alcohol related liver disease: acute management Stuart McPherson, Michael R Lucey, Kieran J Moriarty

Pancreatic cancer Incretin based drugs and the risk of pancreatic cancer: international multicentre cohort study Laurent Azoulay, Kristian B Filion, Robert W Platt, Matthew Dahl, Colin R Dormuth, Kristin K Clemens, Madeleine Durand, David N Juurlink, Laura E Targownik, Tanvir C Turin, J Michael Paterson, Pierre Ernst, for the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators The safety of incretin based drug treatments for type 2 diabetes Shari D Bolen, Nisa M Maruthur Radiotherapy One in seven colorectal cancer patients is under 50, US study shows Jacqui Wise Short intensive radiation courses may work as well as standard ones David Spurgeon Screening (oncology) Case Review: Headaches and hormones: a potentially lethal combination Ramdeep Bajwa, Paven Preet Kaur, Alessandro Paluzzi Statistics Notes: Inverse probability weighting Mohammad Ali Mansournia, Douglas G Altman Atypical glandular cells on cervical cytology Marie-Hélène Mayrand, Anita Koushik Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide cohort study Jiangrong Wang, Bengt Andrae, Karin Sundström, Peter Ström, Alexander Ploner, K Miriam Elfström, Lisen Arnheim-Dahlström, Joakim Dillner, Pär Sparén

C. In brief: Association of SLCO2B1 Genotypes With Outcomes in Patients With Prostate Cancer

New and emerging developments in extensive-stage small cell lung cancer therapeutics Mamta Parikh, Jonathan Riess et al

Current Opinion in Oncology 2016 28 (2) p97-103

Treatment of melanoma brain metastases Simone M Goldinger, Cedric Panje, Paul Nathan Current Opinion in Oncology 2016 28 (2) p159-165

Global strategies for cervical cancer prevention Sharmila Pimple, Gauravi Mishra, Surendra Shastri Current Opinion in Obstetrics & Gynecology 2016 28 (1) p4-10

Infusion-related risks associated with chemotherapy Elizabeth Gallimore Nursing Standard 2016 30 (25) p51-60

For automated tables of contents: Oncology â&#x20AC;&#x201C; click here Haematology â&#x20AC;&#x201C; click here.

NEW BOOKS BACK TO TOP

If you are unable to find a book, or require a book that is not on this list, please ask library staff who will be able to locate the book for you using interlibrary loan.

Haematology (2nd ed) (2016) Moore, Gary W.; Knight, Gavin; Blann, Andrew D. ____________________________________________________ Postgraduate haematology (7th ed) (2016) Higgs, Douglas R. ____________________________________________________ Williams hematology (9th ed) (2016) Kaushansky, Kenneth ____________________________________________________ Practical radiation oncology physics : a companion to Gunderson and Tepper's clinical radiation oncology (2016) Dieterich, Sonja ____________________________________________________ Clinical radiation oncology (4th ed) (2016) Gunderson, Leonard L.; Tepper, Joel E ____________________________________________________ Problem solving in older cancer patients (2016) Ring, Alistair ____________________________________________________ Women's cancers : pathways to living (2016) Smith, J. Richard; Del Priore, Giuseppe ____________________________________________________ Radiation protection in medical imaging and radiation oncology (2016) Vetter, Richard J.; Stoeva, Magdalena S. ____________________________________________________ Oxford textbook of oncology (3rd ed) (2016) Kerr, David J.

COCHRANE REVIEWS/UPDATES BACK TO TOP

Meditation for adults with haematological malignancies Salhofer Ines, Will Andrea, Monsef Ina, Skoetz Nicole Cochrane Database of Systematic Reviews, 2016, 2 We included only one small trial published as an abstract article. The included study investigated the effects of meditation practice on patients newly hospitalised with acute leukaemia. Ninety-one participants enrolled in the study, but only 42 participants remained in the trial throughout the sixmonth follow-up period and were eligible for analysis. There was no information provided about the average age and sex of the study population. We found a high risk for attrition bias and unclear risk for reporting bias, performance and detection bias because of missing data due to abstract publication only, thus we judged the overall risk of bias as high. According to the GRADE criteria, we judged the overall quality of the body of evidence for all predefined outcomes as 'very low', due to the extent of missing data on the study population, and the small sample size. As the abstract publication did not provide numbers and results except P values, we are not able to give more details.Meditation practice might be beneficial for the quality of life of haematologicallydiseased patients, with higher scores for participants in the mediation arms compared to the participants in the usual care control group (low quality of evidence). Levels of depression decreased for those practising meditation in both the spiritually-framed meditation group and the secularly-focused meditation group in comparison to the usual care control group, whose levels of depression remained constant (low quality of evidence). The influence of meditation practice on overall survival, fatigue, anxiety, quality of sleep and adverse events remained unclear, as these outcomes were not evaluated in the included trial.Authors' conclusions: To estimate the effects of meditation practice for patients suffering from haematological malignancies, more high quality randomised controlled trials are needed. At present there is not enough information available on the effects of meditation in haematologically-diseased patients to draw any conclusion.

Interventions for sexual dysfunction following treatments for cancer in women Candy Bridget, Jones Louise, Vickerstaff Victoria, Tookman Adrian, King Michael Cochrane Database of Systematic Reviews, 2016. NO: 2

AB: Background: The proportion of people living with and surviving cancer is growing. This has led to increased awareness of the importance of quality of life, including sexual function, in those affected by cancer. Sexual dysfunction is a potential long-term complication of many cancer treatments. This includes treatments that have a direct impact on the pelvic area and genitals, and also treatments that have a more generalised (systemic) impact on sexual function.This is an update of the original Cochrane review published in Issue 4, 2007, on interventions for treating sexual dysfunction following treatments for cancer for men and women. Since publication in 2007, there has been an increase in the number of trials for both men and women and this current review critiques only those for women. A review in press will present those for men.Objectives: To evaluate the effectiveness of interventions for treating sexual dysfunction in women following treatments for cancer. To assess adverse events associated with interventions.Search methods: We searched the Cochrane Central Register of Controlled Trials (CENTRAL 2015, Issue 9), MEDLINE, EMBASE, PsycINFO, AMED, CINAHL, Dissertation Abstracts and the NHS Research Register. The searches were originally run in January 2007 and we updated these to September 2015.Selection criteria: We included randomised controlled trials (RCTs) that assessed the effectiveness of a treatment for sexual dysfunction. The trial participants were women who had developed sexual dysfunction as a consequence of a cancer treatment. We sought evaluations of interventions that were pharmaceutical, mechanical, psychotherapeutic, complementary or that involved physical exercise.Data collection and analysis: Two review authors independently extracted the data and assessed trial quality. We considered meta-analysis for trials with comparable key characteristics.Main results: Since the original version of this review we have identified 11 new studies in women. The one study identified in the earlier version of this review was excluded in this update as it did not meet our narrower inclusion criteria to include only interventions for the treatment, not prevention, of sexual dysfunction.In total 1509 female participants were randomised across 11 trials. All trials explored interventions following treatment either for gynaecological or breast cancer. Eight trials evaluated a psychotherapeutic or psychoeducational intervention. Two trials evaluated a pharmaceutical intervention and one pelvic floor exercises. All involved heterosexual women. Eight studies were at a high risk of bias as they involved a sample of fewer than 50 participants per trial arm. The trials varied not only in intervention content but in outcome measurements, thereby restricting combined analysis. In the trials evaluating a psychotherapeutic intervention the effect on sexual dysfunction was mixed; in three trials benefit was found for some measures of sexual function and in five trials no benefit was found. Evidence from the other three trials, two on different pharmaceutical applications and one on exercise, differed and was limited by small sample sizes. Only the trial of a pH-balanced vaginal gel found significant improvements in sexual function. The trials of pharmaceutical interventions measured harm: neither reported any. Only one psychological intervention trial reported that no harm occurred because of the intervention; the other trials of psychological support did not measure harm.Authors' conclusions: Since the last version of this review, the new studies do not provide clear information on the impact of interventions for sexual dysfunction following treatments for cancer in women. The sexual dysfunction interventions in this review are not representative of the range that is available for women, or of the wider range of cancers in which treatments are known to increase the risk of sexual problems. Further evaluations are needed.

Surgery for the resolution of symptoms in malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer Cousins Sarah E, Tempest Emma, Feuer David J

Cochrane Database of Systematic Reviews, 2016, No. 1 Main results: In total we have identified 43 studies examining 4265 participants. The original review included 938 patients from 25 studies. The updated search identified an additional 18 studies with a combined total of 3327 participants between 1997 and June 2015. The results of these studies did not change the conclusions of the original review.No firm conclusions can be drawn from the many retrospective case series so the role of surgery in malignant bowel obstruction remains controversial. Clinical resolution varies from 26.7% to over 68%, though it is often unclear how this is defined. Despite being an inadequate proxy for symptom resolution or quality of life, the ability to feed orally was a popular outcome measure, with success rates ranging from 30% to 100%. Rates of re-obstruction varied, ranging from 0% to 63%, though time to re-obstruction was often not included. Postoperative morbidity and mortality also varied widely, although again the definition of both of these surgical outcomes differed between many of the papers. There were no data available for quality of life. The reporting of adverse effects was variable and this has been described where available. Where discussed, surgical procedures varied considerably and outcomes were not reported by specific intervention. Using the 'Risk of bias' assessment tool, most included studies were at high risk of bias for most domains.Authors' conclusions: The role of surgery in malignant bowel obstruction needs careful evaluation, using validated outcome measures of symptom control and quality of life scores. Further information could include re-obstruction rates together with the morbidity associated with the various surgical procedures. Currently, bowel obstruction is managed empirically and there are marked variations in clinical practice by different units. In order to compare outcomes in malignant bowel obstruction, there needs to be a greater degree of standardisation of management.Since the last version of this review none of the new included studies have provided additional information to change the conclusions.

Chinese herbal medicine for oesophageal cancer Chen Xi, Deng Linyu, Jiang Xuehua, Wu Taixiang Cochrane Database of Systematic Reviews, 2016, NO: 1 Nine studies reported a series of adverse events caused by radiotherapy or chemotherapy at the end of the intervention, including mucositis, radiation oesophagitis, arrest of bone marrow, gastrointestinal reactions, renal and hepatic impairment, white blood cell descent, neurotoxicity, cardiac toxicity and anaemia. For those containing multiple studies, we conducted a pooled analysis. As a result, TCM showed a significant effect on radiation oesophagitis (RR 0.66, 95% CI 0.47 to 0.94; 2 RCTs, 90 participants), gastrointestinal reactions (RR 0.54, 95% CI 0.36 to 0.81; 4 RCTs, 268 participants) and white blood cell descent (RR 0.60, 95% CI 0.44 to 0.83; 4 RCTs, 224 participants). The quality of evidence was low or very low, downgrading for risk of bias and imprecision.Authors' conclusions: We currently find no evidence to determine whether TCM is an effective treatment for oesophageal cancer. The effect of TCM on short-term therapeutic effects is uncertain. TCM probably has positive effects on quality of life and on some adverse events caused by radiotherapy or chemotherapy in advanced oesophageal cancer patients undergoing radiotherapy or chemotherapy. The results of the review need to be interpreted cautiously owing to overall low quality evidence. Future trials should be large and correctly designed to detect important clinical effects and minimise risk of bias.

Intraperitoneal chemotherapy for the initial management of primary epithelial ovarian cancer

Jaaback Kenneth, Johnson Nick, Lawrie Theresa A Cochrane Database of Systematic Reviews, 2016, NO: 1 Intraperitoneal chemotherapy increases overall survival and progression-free survival from advanced ovarian cancer. The results of this meta-analysis provide the most reliable estimates of the relative survival benefits of IP over IV therapy and should be used as part of the decision making process. However, the potential for catheter related complications and toxicity needs to be considered when deciding on the most appropriate treatment for each individual woman. The optimal dose, timing and mechanism of administration cannot be addressed from this metaanalysis. This needs to be addressed in the next phase of clinical trials.

Interval debulking surgery for advanced epithelial ovarian cancer Tangjitgamol Siriwan, Manusirivithaya Sumonmal, Laopaiboon Malinee, Lumbiganon Pisake, Bryant Andrew Cochrane Database of Systematic Reviews, 2016, NO: 1 Three RCTs randomising 853 women, of whom 781 were evaluated, met the inclusion criteria. Meta-analysis of three trials for overall survival (OS) found no statistically significant difference between IDS and chemotherapy alone (hazard ratio (HR) = 0.80, 95% confidence interval (CI) 0.61 to 1.06, I² = 58%). Subgroup analysis for OS in two trials, where the primary surgery was not performed by gynaecologic oncologists or was less extensive, showed a benefit of IDS (HR = 0.68, 95% CI 0.53 to 0.87, I² = 0%). Meta-analysis of two trials for PFS found no statistically significant difference between IDS and chemotherapy alone (HR = 0.88, 95% CI 0.57 to 1.33, I² = 83%). Rates of toxic reactions to chemotherapy were similar in both arms (risk ratio = 1.19, 95% CI 0.53 to 2.66, I² = 0%), but little information was available for other adverse events or quality or life (QoL).Authors' conclusions: We found no conclusive evidence to determine whether IDS between cycles of chemotherapy would improve or decrease the survival rates of women with advanced ovarian cancer, compared with conventional treatment of primary surgery followed by adjuvant chemotherapy. IDS appeared to yield benefit only in women whose primary surgery was not performed by gynaecologic oncologists or was less extensive. Data on QoL and adverse events were inconclusive.

Effectiveness of tranexamic acid in reducing blood loss during cytoreductive surgery for advanced ovarian cancer Kietpeerakool Chumnan, Supoken Amornrat, Laopaiboon Malinee, Lumbiganon Pisake Cochrane Database of Systematic Reviews, 2016, NO: 1 Currently, there is insufficient evidence to recommend the routine use of tranexamic acid for reducing blood loss in women undergoing cytoreductive surgery for advanced EOC, as only limited data are available from a single, low quality RCT at low overall risk of bias.

OTHER EVIDENCE UPDATES BACK TO TOP

Note: you may need to logon via Athens when clicking on links in this section.

Up-to-date latest: click here (you may need to logon via Athens)

Dynamed updates (you may need to logon via Athens): click here IMPORTANT: Dynamed subscription finishes end of March. Via BMJ Evidence Updates:

Anastrozole versus tamoxifen for the prevention of locoregional and contralateral breast cancer in postmenopausal women with locally excised ductal carcinoma in situ (IBIS-II DCIS): a double-blind, randomised controlled trial. Lancet

Limited screening with versus without F-fluorodeoxyglucose PET/CT for occult malignancy in unprovoked venous thromboembolism: an open-label randomised controlled trial. Lancet Oncol

Randomized Phase III Trial of Standard Therapy Plus Low Molecular Weight Heparin in Patients With Lung Cancer: FRAGMATIC Trial. J Clin Oncol

Ibrutinib combined with bendamustine and rituximab compared with placebo, bendamustine, and rituximab for previously treated chronic lymphocytic leukaemia or small lymphocytic lymphoma (HELIOS): a randomised, double-blind, phase 3 study.

Lancet Oncol

Systematic review of axillary reverse mapping in breast cancer. Br J Surg

Utilization and Outcomes of Ovarian Conservation in Premenopausal Women With Endometrial Cancer. Obstet Gynecol

Etirinotecan pegol (NKTR-102) versus treatment of physician`s choice in women with advanced breast cancer previously treated with an anthracycline, a taxane, and capecitabine (BEACON): a randomised, open-label, multicentre, phase 3 trial. Lancet Oncol

Lapatinib in Combination With Capecitabine Plus Oxaliplatin in Human Epidermal Growth Factor Receptor 2-Positive Advanced or Metastatic Gastric, Esophageal, or Gastroesophageal Adenocarcinoma: TRIO-013/LOGiC- A Randomized Phase III Trial. J Clin Oncol

Chemotherapy plus lenalidomide versus autologous transplantation, followed by lenalidomide plus prednisone versus lenalidomide maintenance, in patients with multiple myeloma: a randomised, multicentre, phase 3 trial. Lancet Oncol

Harms of Breast Cancer Screening: Systematic Review to Update the 2009 U.S. Preventive Services Task Force Recommendation. Ann Intern Med

Ovarian cancer screening and mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): a randomised controlled trial. Lancet

Carfilzomib and dexamethasone versus bortezomib and dexamethasone for patients with relapsed or refractory multiple myeloma (ENDEAVOR): a randomised, phase 3, open-label, multicentre study. Lancet Oncol

Effectiveness of tranexamic acid in reducing blood loss during cytoreductive surgery for advanced ovarian cancer. Cochrane Database Syst Rev

Long-Term Results of the HD2000 Trial Comparing ABVD Versus BEACOPP Versus COPPEBV-CAD in Untreated Patients With Advanced Hodgkin Lymphoma: A Study by Fondazione Italiana Linfomi. J Clin Oncol

Supportive management strategies for disseminated intravascular coagulation. An international consensus. Thromb Haemost

Adjuvant Lapatinib and Trastuzumab for Early Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer: Results From the Randomized Phase III Adjuvant Lapatinib and/or Trastuzumab Treatment Optimization Trial. J Clin Oncol

Preoperative Pelvic Floor Muscle Exercise and Postprostatectomy Incontinence: A Systematic Review and Meta-analysis. Eur Urol

Hyperbaric oxygen for patients with chronic bowel dysfunction after pelvic radiotherapy (HOT2): a randomised, double-blind, sham-controlled phase 3 trial. Lancet Oncol

Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): survival results from an adaptive, multiarm, multistage, 20

platform randomised controlled trial. Lancet

Bendamustine plus rituximab versus fludarabine plus rituximab for patients with relapsed indolent and mantle-cell lymphomas: a multicentre, randomised, open-label, noninferiority phase 3 trial. Lancet Oncol

Rituximab Maintenance for a Maximum of 5 Years After Single-Agent Rituximab Induction in Follicular Lymphoma: Results of the Randomized Controlled Phase III Trial SAKK 35/03. J Clin Oncol

Systematic Review and Meta-Analysis of the Effects of Exercise for Those With CancerRelated Lymphedema. Arch Phys Med Rehabil

Pooled long-term outcomes from two randomized trials of axillary node sampling with axillary radiotherapy versus axillary node clearance in patients with operable node-positive breast cancer. Br J Surg

Efficacy and safety of enzalutamide versus bicalutamide for patients with metastatic prostate cancer (TERRAIN): a randomised, double-blind, phase 2 study. Lancet Oncol

Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone-sensitive prostate cancer: a systematic review and meta-analyses of aggregate data. Lancet Oncol

Pretreatment with anti-thymocyte globulin versus no anti-thymocyte globulin in patients with haematological malignancies undergoing haemopoietic cell transplantation from 21

unrelated donors: a randomised, controlled, open-label, phase 3, multicentre trial. Lancet Oncol

Hypercoagulabilty, venous thromboembolism, and death in patients with cancer. A MultiState Model. Thromb Haemost

Long-term remissions after FCR chemoimmunotherapy in previously untreated patients with CLL: updated results of the CLL8 trial. Blood

Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia. Blood

The role of iron in the management of chemotherapy-induced anemia in cancer patients receiving erythropoiesis-stimulating agents. Cochrane Database Syst Rev

NICE guidance:

NICE guidance on olaparib for maintenance treatment of patients with relapsed, platinum-sensitive, BRCA mutation-positive ovarian cancer The National Institute for Health and Care Excellence (NICE) has published guidance recommending olaparib as a treatment option for patients with relapsed, platinumsensitive ovarian cancer, fallopian tube cancer, or peritoneal cancer who have BRCA1 or BRCA2 mutations and whose disease has responded to subsequent plantinumbased chemotherapy.

NICE guidance on panobinostat for patients with multiple myeloma after at least two previous treatments 22

NICE has published guidance recommending panobinostat in combination with bortezomib and dexamethasone as an option for adults with relapsed or relapsed and refractory multiple myeloma who have received at least two previous regimens, including bortezomib and an immunomodulatory agent, if the company provides panobinostat with the discount agreed in the patient access scheme.

NICE guidance on radiumâ&#x20AC;&#x201C;223 dichloride for hormoneâ&#x20AC;&#x201C;relapsed prostate cancer with bone metastases NICE has published guidance recommending radium-223 dichloride as an option for treating adults with hormone-relapsed prostate cancer, symptomatic bone metastases, and no known visceral metastases only if they have had treatment with docetaxel and if Bayer (Newbury, UK) provides radium-223 dichloride with the discount agreed in the patient access scheme.

Myeloma: diagnosis and management (NG35) this guideline covers the diagnosing and managing of myeloma (including smouldering myeloma and primary plasma cell leukaemia) in people aged 16 and over. It aims to improve care for people with myeloma by promoting the most effective tests and treatments for myeloma and its complications

Cancer of the upper aerodigestive tract: assessment and management in people aged 16 and over (NG36) This guideline covers assessing and managing cancers of the upper aerodigestive tract in young people (aged 16 and over) and adults. It aims to reduce variation in practice and improve survival.

Nivolumab for treating advanced (unresectable or metastatic) melanoma Nivolumab as monotherapy is recommended, within its marketing authorisation, as an option for treating advanced (unresectable or metastatic) melanoma in adults.

Also from NICE: 23

Ramucirumab for treating advanced gastric cancer or gastroâ&#x20AC;&#x201C;oesophageal Non-Hodgkin's lymphoma : Draft guidance consultation Enzalutamide for treating metastatic hormone-relapsed prostate cancer before chemotherapy is indicated.

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CANCER IN THE NEWS BACK TO TOP

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Chemotherapy drug boosts survival for newly diagnosed prostate cancer

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The death of cancer? Part 1: the birth of effective drug therapy

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More People Under 50 Getting Colon Cancer, Analysis Finds

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Prognostic Score Helps Target Post-Op Radiotherapy To High-Risk DCIS Patients

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Extended Follow-Up Supports Dabrafenib Plus Trametinib in Metastatic BRAF-mutated Melanoma

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TWiST Results Favour Pazopanib For Metastatic RCC

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Survival After Metastases May Be Predicted In Breast Cancer Patients

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Gastrectomy ‘Not Justified’ For Advanced Gastric Cancer With Single Incurable Metastatic Site

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Prostate Cancer: Driving the Personalized Medicine Highway

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Proton beam therapy 'effective' and 'causes fewer side effects'

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Hope that blood test 'could diagnose five types of cancer'

REPORTS, PUBLICATIONS AND RESOURCES

Prostate cancer treatment NHS England has announced patients first diagnosed with advanced prostate cancer will now get immediate access to a drug which studies have shown can extend their life by more than a year compared to current options. Following a review of evidence from two trials published late last year, specialists will now be able to prescribe the chemotherapy drug docetaxel as soon as someone is diagnosed with incurable prostate cancer. Under previous guidelines, patients had to wait until it was clear that existing, hormone-based treatments had stopped having an effect. To read more click here.

Sepsis Action Plan NHS England published an action plan to address sepsis within the NHS. This document sets out how sepsis deaths can be reduced and actions that need to be taken to reduce the number of sepsis deaths in England but is also applicable across the UK. Click here for more www.england.nhs.uk/wp-content/uploads/2015/08/Sepsis-Action-Plan-23.12.15v1.pdf

Inadvisable breast and prostate cancer screenings in the USA Results of a new analysis indicate that the frequency of breast cancer and prostate cancer screenings in elderly patients with short life expectancies—practices that are viewed as inadvisable—significantly vary throughout the USA and that the nationwide prevalence of such screenings is about 16%. Read this Report →

Prediction of chemotherapy benefit for colon cancers CDX2 expression has been identified as a prognostic biomarker for stage II and III colon cancers that might be treatable with adjuvant chemotherapy. Read this Report →

2016 ASCO Gastrointestinal Cancers Symposium Findings from the 2016 ASCO Gastrointestinal Cancers Symposium, which was held in San Francisco, CA, USA, Jan 21–23, 2016. Read this Report →

Counting the cost of end-of-life cancer care Two new studies have examined end-of-life care for patients with cancer. Alexi Wright and colleagues assessed data for US patients on Medicare who died from lung or colorectal cancer before the end of 2011. The second study retrospectively compared differences in end-of-life care for patients with cancer who died in 2010 in several Western European and North American nations. Read this Report →

US FDA's safety monitoring of drugs with expedited approval Expedited drug approvals might be putting patients at risk, suggests a US Government Accountability Office (GAO) performance audit of the Center for Drug Evaluation and Research (CDER) at the US Food and Drug Administration (FDA). Read this Report →

Increase in illicit cigarette consumption in Brazil

According to a new study, illicit trade and consumption of cigarettes in Brazil has increased substantially in recent y prevalence, as a result of the government's initiatives to increase tobacco taxes. Read this Report →

TRAINING & NETWORKING OPPORTUNITIES, CONFERENCES, EVENTS BACK TO TOP

ESO, CNIO and NRCO Conference on Familial Cancer 19-20 May 2016, Madrid, Spain Find out more

The 62nd Annual Scientific and Standardization Committee (SSC) Meeting of the ISTH Takes place in Montpellier, France, May 25-28, 2016. In order to get the best rates for this engaging and insightful conference, please register by February 10.

OTHER SERVICES BACK TO TOP A. Literature & Evidence searches 

Are you looking for the latest evidence-based research, but haven’t got time to trawl the databases?

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Do you need a literature search carried out?

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Do you need to find evidence to support an improvement?

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Do you want to know how something has been done elsewhere and whether it worked?

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Library staff provide a literature and evidence search service for busy clinicians who are pressed for time.

To request a search, please complete and return this form, providing as much information as possible. Alternatively if you would like an assisted search training session, where we will sit down with you and go through the steps of a literature search, then please contact the library. B. Journal clubs Do you have a journal club or are thinking of starting one up? If so, please contact the Library. We will be happy to attend any new or existing journal club in a contributory or facilitating role.

TRAINING AND ATHENS BACK TO TOP

Most electronic resources are available via an Athens password. You can register for this via the Library intranet page, or from home at http://www.swice.nhs.uk/ and following the link for Athens self-registration. Please note that registering from home will take longer as it will need to be verified that you are NHS staff/student on placement. Library staff are available to train individual staff or small groups. Training can take place in the library or at your work place if you have access to appropriate IT facilities. COURSES INCLUDE: Library Induction You will be given a detailed overview of all library information systems and resources and how to use them. Library registration and obtaining an OpenAthens password are included. Accessing NHS eResources You will be introduced to all the electronic information resources available to NHS staff including eJournals, eBooks, healthcare databases and useful websites.

Searching for Evidence (beginners) You will be introduced to the 8 leading healthcare databases and shown how to plan your literature search, how to execute it effectively and how to save and print your results. Searching for Evidence (advanced) You will be shown how to search across multiple databases, how to use the thesaurus, the subject headings and the full range of limit options. Introduction to Critical Appraisal This course introduces the basics of critical appraisal and its role in evidence-based practice. Pre-Course Skills Parts 1 & 2 These 2 sessions are designed for staff about to start a course who need a thorough update on information gathering skills. Attendance at both sessions is required. Library Mini-Breaks 30 minute sessions tailored to meet your needs e.g. Cochrane Library, how to find clinical guidelines, using eBooks, library electronic A-Z website, RSS feeds, journal contents pages using Outlook. Rapid Evidence Searching NEW Using tried and tested techniques, rapid searching of the evidence base for when quick solutions are needed. Reflective Practice NEW How to read and comment upon a paper Writing for publication NEW Everything you need to know about writing a paper for publication Collaborative "Living Evidence" Searching/Appraisal NEW Group searching/appraisal of evidence in computer labs (suitable for MDTs and similar).

TO BOOK A COURSE, click here