May 2016 cancer current awareness2 by Musgrove Park Hospital Library

Clinical Librarian Service Musgrove Park Academy

Current Awareness

Cancer Issue 5 May 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

Other 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

The impact of cancer incidence and stage on optimal utilization of radiotherapy: Methodology of a population based analysis by the ESTRO-HERO project Radiotherapy & Oncology July 2015Volume 116, Issue 1, Pages 45–50 This methodology can be adapted using European data, thus facilitating the planning of resources required to cope with the demand for radiotherapy in Europe, taking into account the national variability in cancer incidence.

The optimal utilization proportion of external beam radiotherapy in European countries: An ESTROHERO analysis Radiotherapy & Oncology July 2015Volume 116, Issue 1, Pages 38–44 The actual utilization of radiotherapy is significantly lower than the optimal use predicted from the evidence based estimates in the literature. This discrepancy poses a major challenge for policy makers when planning the resources at the national level to improve the provision in European countries

PET-CT Surveillance versus Neck Dissection in Advanced Head and Neck Cancer New England Journal of Medicine, March 23, 2016 Survival was similar among patients who underwent PET-CT–guided surveillance and those who underwent planned neck dissection, but surveillance resulted in considerably fewer operations and it was more cost-effective.

Coffee Consumption and the Risk of Colorectal Cancer Cancer Epidemiol Biomarkers Prev April 2016 25; 634

Coffee consumption may be inversely associated with risk of colorectal cancer in a dose–response manner. Global coffee consumption patterns suggest potential health benefits of the beverage for reducing the risk of colorectal cancer.

Absolute Benefit of Adjuvant Endocrine Therapies for Premenopausal Women With Hormone Receptor–Positive, Human Epidermal Growth Factor Receptor 2–Negative Early Breast Cancer: TEXT and SOFT Trials Journal of Clinical Oncology April 20, 2016, 34 (12) Authors: various Premenopausal women with hormone receptor–positive, HER2-negative disease and high recurrence risk, as defined by clinicopathologic characteristics, may experience improvement of 10% to 15% in 5-year BCFI with exemestane plus OFS versus tamoxifen alone. An improvement of at least 5% may be achieved for women at intermediate risk, and improvement is minimal for those at lowest risk

Multicenter cohort study on the survival time of cancer patients dying at home or in a hospital: Does place matter? Jun Hamano, Takashi Yamaguchi, Isseki Maeda et al. Cancer, Article first published online: 28 MAR 2016. Among the 2426 patients recruited, 2069 patients were analyzed for this study: 1582 receiving hospital-based palliative care and 487 receiving home-based palliative care. A total of 1607 patients actually died in a hospital, and 462 patients died at home. The survival of patients who died at home was significantly longer than the survival of patients who died in a hospital in the days' prognosis group (estimated median survival time, 13 days [95% confidence interval (CI), 10.3-15.7 days] vs 9 days [95% CI, 8.0-10.0 days]; P = .006) and in the weeks' prognosis group (36 days [95% CI, 29.9-42.1 days] vs 29 days [95% CI, 26.5-31.5 days]; P = .007) as defined by Prognosis in Palliative Care Study predictor model A. No significant difference was identified in the months' prognosis group. Cox proportional hazards analysis revealed that the place of death had a significant influence on the survival time in both unadjusted (hazard ratio [HR], 0.86; 95% CI, 0.78-0.96; P < .01) and adjusted models (HR, 0.87; 95% CI, 0.77-0.97; P = .01). In comparison with cancer patients who died in a hospital, cancer patients who died at home had similar or longer survival. Cancer 2015. © 2015 American Cancer Society.

Gefitinib vs. Erlotinib for Previously Treated Advanced Lung Adenocarcinoma Anne S. Tsao, MD Reviewing Urata Y et al., J Clin Oncol 2016 Mar 28; 4

The trial did not meet its primary endpoint of noninferiority for gefitinib in terms of progression-free survival. Four epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors are currently FDAapproved for EGFR-mutated nonâ&#x20AC;&#x201C;small-cell lung cancer (NSCLC). In frontline EGFR-mutated patients, afatinib, gefitinib, and erlotinib are available, and osimertinib is approved for T790M patients. Gefitinib and erlotinib are also approved for salvage use in EGFRâ&#x20AC;&#x201C;wild-type NSCLC. Now, the West Japan Oncology Group has conducted a multicenter, randomized, open-label, noninferiority, phase III trial (WJOG 5108L), in which 561 previously chemotherapy-treated patients with advanced lung adenocarcinoma (71% had EGFR mutations) were randomized to receive gefitinib or erlotinib. The primary endpoint was progression-free survival (PFS) noninferiority with gefitinib.

Clonal neoantigens elicit T cell immunoreactivity and sensitivity to immune checkpoint blockade Nicholas McGranahan, Andrew J. S. Furness, Rachel Rosenthal Science 03 Mar 2016: As tumors grow they acquire mutations, some of which create neoantigens that influence the response of patients to immune checkpoint inhibitors. We explored the impact of neoantigen intratumor heterogeneity (ITH) on anti-tumor immunity. Through integrated analysis of ITH and neoantigen burden, we demonstrate a relationship between clonal neoantigen burden and overall survival in primary lung adenocarcinomas (n = 139). CD8+ tumor-infiltrating lymphocytes reactive to clonal neoantigens were identified in early-stage non-small cell lung cancer (NSCLC) and expressed high levels of PD-1. Sensitivity to PD-1 and CTLA-4 blockade in patients with advanced NSCLC (n = 31) and melanoma (n = 135) was enhanced in tumors enriched for clonal neoantigens. T cells recognizing clonal neoantigens were detectable in patients with durable clinical benefit. Cytotoxic chemotherapy-induced subclonal neoantigens, contributing to an increased mutational load, were enriched in certain poor responders. These data suggest that neoantigen heterogeneity may influence immune surveillance and support therapeutic developments targeting clonal neoantigens.

What Are Risks for Second Cancers After Prostate Radiotherapy? Robert Dreicer, MD, MS, FACP, FASCO Reviewing Eyler CE and Zietman ALA., BMJ 2016 Mar 2; 352:i1073 The risk for second cancers is well recognized in patients who receive therapeutic radiation for Hodgkin lymphoma, breast cancer, and testicular cancer. But whether this risk is also increased in patients who receive radiotherapy for prostate cancer is unclear. To determine the potential association between prostate radiotherapy and subsequent second cancers, investigators conducted a meta-analysis of 18 large multicenter studies and 3 single-center studies involving prostate cancer patients who received radiotherapy (mostly conformal external beam radiotherapy) versus surgery (in 13 studies) or versus either no radiotherapy or no radiotherapy and no surgery (in 8 studies). The primary outcome was development of secondary bladder, colorectal, lung, or hematologic cancer. The lag time from radiotherapy to development of second cancer was analyzed during 5-year and 5

10-year periods. Compared with patients unexposed to radiotherapy, those who received radiotherapy had increased risks for secondary bladder cancer (hazard ratio, 1.67), colorectal cancer (HR, 1.79), and rectal cancer (HR, 1.79). No increased risks were seen for lung or hematologic malignancies. Rates of second cancers ranged from 0.1% to 3.8% for bladder cancer, 0.3% to 4.2% for colon cancer, and 0.3% to 1.2% for rectal cancer. Risks for second cancers were much higher with external beam radiotherapy than with brachytherapy.

Another Adjuvant Option for Ductal Carcinoma In Situ William J. Gradishar, MD Reviewing Margolese RG et al., Lancet 2016 Feb 27; 387:849 Anastrozole is superior to tamoxifen in postmenopausal ER-positive DCIS patients younger than 60. Aromatase inhibitors (AIs) have proven to be effective for women with estrogen receptor (ER)positive breast cancer, as both adjuvant and late-stage treatments, and recently they have been shown to be an option in the prevention setting. Now, investigators have conducted a randomized, double-blind, phase III trial (NASBP B-35) comparing tamoxifen with the nonsteroidal AI anastrozole as adjuvant treatment for 3104 postmenopausal women with ER-positive ductal carcinoma in situ (DCIS). All patients had undergone lumpectomy with clear margins followed by whole-breast irradiation. Patients were randomized to tamoxifen (20 mg daily) or anastrozole (1 mg daily) and were stratified by age (<60 vs. â&#x2030;Ľ60 years). The primary endpoint of the study was the breast cancerâ&#x20AC;&#x201C; free interval from randomization to any breast cancerâ&#x20AC;&#x201C;related event. At a median follow-up of 9 years, fewer cancer-related events had occurred with anastrozole than with tamoxifen (90 vs. 122; hazard ratio, 0.73; P=0.023). However, anastrozole was superior to tamoxifen only in patients younger than age 60. Both drugs were well tolerated, though, as expected, the rate of thrombotic events was higher with tamoxifen (2.7% vs. 0.8%).

Managing Cancer Pain: Two Randomized Trials Allan S. Brett, MD Reviewing Raman S et al., J Clin Oncol 2016 Feb 20; 34:524 Two recent studies in the Journal of Clinical Oncology add to our understanding of cancer pain treatments. The World Health Organization's traditional three-step analgesic ladder consists of nonopioids, weak opioids, and strong opioids for treating patients with mild, mild-to-moderate, and moderate-to-severe cancer pain, respectively. But some experts argue that skipping weak opioids (step 2) and moving directly to low doses of so-called strong opioids (e.g., morphine) is reasonable when nonopioid analgesics are inadequate. In an open-label randomized trial from Italy, researchers assigned 240 opioid-naive cancer patients with moderate pain to receive either step-2 analgesics (codeine or tramadol, usually combined with acetaminophen and titrated to maximal recommended doses) or oral immediate-release morphine (starting with 5 mg every 4 hours and transitioning eventually to slow-release equivalent dosage). During 4 weeks of follow-up, the morphine group achieved better pain control than did the weak-opioid group, with no higher incidence of side 6

effects. In a randomized double-blind trial from the U.K., researchers addressed the uncertain effectiveness of the anticonvulsant analgesic pregabalin for painful bone metastases in 233 patients, most of whom had breast, lung, or prostate cancer. Patients received radiotherapy plus 1 month of either pregabalin (titrated to a maximum dose of 300 mg twice daily) or placebo. At 1 month, the proportion of patients with adequate pain relief was virtually identical in both groups.

MYC regulates the antitumor immune response through CD47 and PD-L1 Stephanie C. Casey, Ling Tong, Yulin Li et al The MYC oncogene codes for a transcription factor that is overexpressed in many human cancers. Here we show that MYC regulates the expression of two immune checkpoint proteins on the tumor cell surface, the innate immune regulator, CD47 (Cluster of Differentiation 47) and the adaptive immune checkpoint, PD-L1 (programmed death-ligand 1). Suppression of MYC in mouse tumors and human tumor cells caused a reduction in the levels of CD47 and PD-L1 mRNA and protein. MYC was found to bind directly to the promoters of the CD47 and PD-L1 genes. MYC inactivation in mouse tumors down-regulated CD47 and PD-L1 expression and enhanced the anti-tumor immune response. In contrast, when MYC was inactivated in tumors with enforced expression of CD47 or PD-L1, the immune response was suppressed and tumors continued to grow. Thus MYC appears to initiate and maintain tumorigenesis in part through the modulation of immune regulatory molecules.

Neutrophil to lymphocyte ratio (NLR) for prediction of distant metastasis-free survival (DMFS) in early breast cancer: a propensity score-matched analysis Michele Orditura, Gennaro Galizia, Anna Diana et al We have, for the first time, analysed the prognostic significance of NLR in a highly selected population of patients with breast cancer, specifically, stage I and IIA breast cancer, by means of propensity score analysis. This statistical procedure was chosen by virtue of its ability to yield robust and scientifically sound results. One limitation of our work lies in the retrospective nature of the study; thus, prospective studies are needed to validate its accuracy prior to introducing NLR assessment in every-day clinical practice for prediction of cancer recurrence

Fulvestrant Plus Palbociclib vs Fulvestrant Plus Placebo for HR+, HER2â&#x201D;&#x20AC; Metastatic Breast Cancer That Progressed on Endocrine Therapy Lancet Oncol; 2016 Mar 3; EPub Ahead of Print; M Cristofanilli, NC Turner, I Bondarenko, et al

A. Miscellaneous The Role of Risk-Reducing Surgery in Hereditary Breast and Ovarian Cancer 7

L.C. Hartmann and N.M. Lindor N Engl J Med 374:454, February 4, 2016 Neratinib After Trastuzumab-Based Adjuvant Therapy in Patients With HER2-Positive Breast Cancer Lancet Oncol; 2016 Feb 10; EPub Ahead of Print; A Chan, S Delaloge, FA Holmes, et al Aspirin may reduce risk of metastases and death in patients with cancer, study finds Susan Mayor

B. In brief (you may need to logon to BMJ to see): Breast cancer Partial breast radiotherapy is as effective as standard whole breast radiotherapy, study finds Jacqui Wise Spot Diagnosis: Interesting case of lymphocytosis and splenomegaly Selina J Chavda, Claire Dearden UK's new alcohol guidelines: Drunk on risk: how the chief medical officersâ&#x20AC;&#x2122; alcohol guidelines are demonising drink David M Shaw Type 1 diabetes is associated with increased risk of several cancers Jacqui Wise A quarter of patients with rarer cancers see GPs several times before referral Susan Mayor I chose reconstruction, but not to look good: Patients having breast reconstruction should enter into surgery with as much information as possible Christopher J Deutsch Coronary artery disease: screen or treat? Darrel P Francis, Graham D Cole 10 minute consultation: Bisphosphonates beyond five years Zoe Paskins, Louise Warburton Rates of prophylactic mastectomy triple in decade, study shows Jacqui Wise People lack awareness of link between alcohol and cancer, survey finds

Anne Gulland

Cancer: dermatological Most melanoma patients have few moles, study finds Ingrid Torjesen Facial cutaneous squamous cell carcinoma Arif M Aslam, Anand N Patel

Chemotherapy Overspending driven by oversized single dose vials of cancer drugs Peter B Bach, Rena M Conti, Raymond J Muller, Geoffrey C Schnorr, Leonard B Saltz New "managed access" process for Cancer Drugs Fund to go ahead, NHS England confirms Susan Mayor Spot Diagnosis: Complications of rhinosinusitis Stephen L Ball, Sean Carrie Laser treatment opens temporary window in blood-brain barrier Jacqui Wise Practice pointer: Treating hypertension in patients with medical comorbidities Lucinda Kennard, Kevin M Oâ&#x20AC;&#x2122;Shaughnessy Easily Missed?: Rheumatoid arthritis Kate Harnden, Colin Pease, Andrew Jackson Female survivors of childhood cancer have good chance of motherhood, study finds Ingrid Torjesen Practice Pointer: Purpuric and petechial rashes in adults and children: initial assessment Angela E Thomas, Susan F Baird, Julia Anderson Methotrexate monotherapy and methotrexate combination therapy with traditional and biologic disease modifying antirheumatic drugs for rheumatoid arthritis: abridged Cochrane systematic review and network meta-analysis Glen S Hazlewood, Cheryl Barnabe, George Tomlinson, Deborah Marshall, Dan Devoe, Claire Bombardier

Haematology (incl blood transfusion)

Effect of restrictive versus liberal transfusion strategies on outcomes in patients with cardiovascular disease in a non-cardiac surgery setting: systematic review and meta-analysis Annemarie B Docherty, Rob Oâ&#x20AC;&#x2122;Donnell, Susan Brunskill, Marialena Trivella, Carolyn Doree, Lars Holst, Martyn Parker, Merete Gregersen, Juliano Pinheiro de Almeida, Timothy S Walsh, Simon J Stanworth

Radiotherapy Partial breast radiotherapy is as effective as standard whole breast radiotherapy, study finds Jacqui Wise A (relatively) risky business: the link between prostatic radiotherapy and second malignancies Christine E Eyler, Anthony L Zietman Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis Christopher J D Wallis, Alyson L Mahar, Richard Choo, Sender Herschorn, Ronald T Kodama, Prakesh S Shah, Cyril Danjoux, Steven A Narod, Robert K Nam

Colon cancer Long term aspirin may reduce overall cancer risk Jacqui Wise A (relatively) risky business: the link between prostatic radiotherapy and second malignancies Christine E Eyler, Anthony L Zietman Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis Christopher J D Wallis, Alyson L Mahar, Richard Choo, Sender Herschorn, Ronald T Kodama, Prakesh S Shah, Cyril Danjoux, Steven A Narod, Robert K Nam US panel recommends low dose aspirin to prevent cardiovascular disease and colorectal cancer Michael McCarthy

Lung cancer (oncology) Long term aspirin may reduce overall cancer risk Jacqui Wise Analysis of matched case-control studies Neil Pearce Easily Missed?: Soft tissue sarcoma N Eastley, P N Green, R U Ashford

Screening (oncology) Long term aspirin may reduce overall cancer risk Jacqui Wise

Spot Diagnosis: Interesting case of lymphocytosis and splenomegaly Selina J Chavda, Claire Dearden Laser treatment opens temporary window in blood-brain barrier Jacqui Wise First cancer patient has new metabolic imaging technique in UK trial Susan Mayor 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 Easily Missed?: Soft tissue sarcoma N Eastley, P N Green, R U Ashford Spot Diagnosis: Abnormality on a plain film chest radiograph James Lowe, David C Howlett 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 Facial cutaneous squamous cell carcinoma Arif M Aslam, Anand N Patel Sharing clinical trial data: Consolidation of regulation in Europe is needed for the ICMJE’s data sharing proposal to work Marc Dewey, Jonathan Dodd Experts call for younger men to be offered PSA test for prostate cancer Adrian O’Dowd Early life radiation exposure: Withholding imaging in pregnancy may be hazardous Kenneth Hodson, Jason Waugh, Catherine Nelson-Piercy 10 minute consultation: Bisphosphonates beyond five years Zoe Paskins, Louise Warburton

Hepatic cancer People lack awareness of link between alcohol and cancer, survey finds Anne Gulland

Prostate cancer 11

A (relatively) risky business: the link between prostatic radiotherapy and second malignancies Christine E Eyler, Anthony L Zietman Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis Christopher J D Wallis, Alyson L Mahar, Richard Choo, Sender Herschorn, Ronald T Kodama, Prakesh S Shah, Cyril Danjoux, Steven A Narod, Robert K Nam Type 1 diabetes is associated with increased risk of several cancers Jacqui Wise Experts call for younger men to be offered PSA test for prostate cancer Adrian O’Dowd

Cancer: small intestine A quarter of patients with rarer cancers see GPs several times before referral Susan Mayor

Urological cancer Second malignancies after radiotherapy for prostate cancer: systematic review and meta-analysis Christopher J D Wallis, Alyson L Mahar, Richard Choo, Sender Herschorn, Ronald T Kodama, Prakesh S Shah, Cyril Danjoux, Steven A Narod, Robert K Nam Type 1 diabetes is associated with increased risk of several cancers Jacqui Wise Pioglitazone use and risk of bladder cancer: population based cohort study Marco Tuccori, Kristian B Filion, Hui Yin, Oriana H Yu, Robert W Platt, Laurent Azoulay Experts call for younger men to be offered PSA test for prostate cancer Adrian O’Dowd

Gynecological cancer Rates of prophylactic mastectomy triple in decade, study shows Jacqui Wise 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 Obesity is blamed for large rise in uterine cancers in UK Zosia Kmietowicz

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.

Objective Structured Clinical Examination : In Intensive Care Medicine Jeyanathan, Jeyasankar; Owens, Daniel The objective structured clinical examination (OSCE) has become widely employed in intensive care medicine (ICM) exams such as the UK Final Fellowship of Intensive Care Medicine (FFICM), the European Diploma of Intensive Care (EDIC) exam, or the Australia and New Zealand Fellowship of the College of Intensive Care Medicine (CICM). This book is not only an essential tool for the rehearsal of OSCEs in preparation for these exams.

Merenstein and Gardner's handbook of neonatal intensive care (8th ed.) (2016) Gardner, Sandra L. Merenstein & Gardner's Handbook of Neonatal Intensive Care, 8th Edition, is the leading resource for collaborative, interprofessional critical care of newborns. Co-authored by physicians and nurses, it offers concise, comprehensive coverage with a unique multidisciplinary approach and realworld perspective that make it an essential guide for both neonatal nurses and physicians. The 8th edition features the latest neonatal research, evidence, clinical guidelines, and practice recommendations all in a practical quick-reference format for easy retrieval and review of key information.

COCHRANE REVIEWS/UPDATES BACK TO TOP

Intraoperative frozen section analysis for the diagnosis of early stage ovarian cancer in suspicious pelvic masses. Ratnavelu NDG, Brown AP, Mallett S, Scholten RJPM, Patel A, Founta C, Galaal K, Cross P, Naik R. Cochrane Database of Systematic Reviews 2016, Issue 3. In a hypothetical population of 1000 patients (290 with cancer and 80 with a borderline tumour), if a frozen section positive test result for invasive cancer alone was used to diagnose cancer, on average 261 women would have a correct diagnosis of a cancer, and 706 women would be correctly diagnosed without a cancer. However, 4 women would be incorrectly diagnosed with a cancer (false positive), and 29 with a cancer would be missed (false negative). If a frozen section result of either an invasive cancer or a borderline tumour was used as a positive test to diagnose cancer, on average 280 women would be correctly diagnosed with a cancer and 635 would be correctly diagnosed without. However, 75 women would be incorrectly diagnosed with a cancer and 10 women with a cancer would be missed. The largest discordance is within the reporting of frozen section borderline tumours. Investigation into factors leading to discordance within centres and standardisation of criteria for reporting borderline tumours may help improve accuracy. Some centres may choose to perform surgical staging in women with frozen section diagnosis of a borderline ovarian tumour to reduce the number of false positives. In their interpretation of this review, readers should evaluate results from studies most typical of their population of patients.

Different dosage schedules for reducing cardiotoxicity in people with cancer receiving anthracycline chemotherapy. Cochrane Database of Systematic Reviews 2016, Issue 3. van Dalen EC, van der Pal HJH, Kremer LCM. An anthracycline infusion duration of six hours or longer reduces the risk of clinical heart failure, and it seems to reduce the risk of subclinical cardiac damage. Since there is only a small amount of data for children and data obtained in adults cannot be extrapolated to children, different anthracycline infusion durations should be evaluated further in children. We identified no significant difference in the occurrence of clinical heart failure in participants treated with a doxorubicin peak dose of less than 60 mg/m2 or 60 mg/m2 or more. Only one RCT was available for the other identified peak doses, so we can make no definitive conclusions about the occurrence of cardiotoxicity. More high-quality research is needed, both in children and adults and in leukaemias and solid tumours.

Pentoxifylline and vitamin E alone or in combination for preventing and treating side effects of radiation therapy and concomitant chemoradiotherapy (Protocol). Cochrane Database of Systematic Reviews 2016, Issue 3. Pareek P, Samdariya S, Sharma A, Gupta N, Shekhar S, Kirubakaran R. This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the following. 

Pentoxifylline or vitamin E, or both, for the prevention or treatment of side effects of therapeutic radiation therapy alone or combined with chemotherapy in people with cancer.

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Adverse effects of either pentoxifylline or vitamin E, or both, when given to people with cancer during radiation therapy alone or combined with chemotherapy.

Intravesical Bacillus Calmette-Guérin with interferon-alpha versus intravesical Bacillus CalmetteGuérin for treating non-muscle-invasive bladder cancer (Protocol). Cochrane Database of Systematic Reviews 2016, Issue 3. Shepherd ARH, Shepherd E, Brook NR. This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of intravesically administered Bacillus Calmette-Guérin (BCG) plus interferon(IFN)alpha(α) compared with BCG alone for treating non-muscle-invasive bladder cancer (NMIBC).

Body weight management in overweight and obese breast cancer survivors (Protocol). Cochrane Database of Systematic Reviews 2016, Issue 3. Ma LX, Bulsara MK, Tan SY, Vardy J. This is the protocol for a review and there is no abstract. The objectives are as follows: To assess the effects of different body weight management approaches in breast cancer survivors who are overweight or obese.

Laparoscopic versus open distal pancreatectomy for pancreatic cancer Deniece Riviere, Kurinchi Selvan Gurusamy, David A Kooby, et al First published: 4 April 2016 Currently, no randomised controlled trials have compared laparoscopic distal pancreatectomy versus open distal pancreatectomy for patients with pancreatic cancers. In observational studies, laparoscopic distal pancreatectomy has been associated with shorter hospital stay as compared with open distal pancreatectomy. Currently, no information is available to determine a causal

association in the differences between laparoscopic versus open distal pancreatectomy. Observed differences may be a result of confounding due to laparoscopic operation on less extensive cancer and open surgery on more extensive cancer. In addition, differences in length of hospital stay are relevant only if laparoscopic and open surgery procedures are equivalent oncologically. This information is not available currently. Thus, randomised controlled trials are needed to compare laparoscopic distal pancreatectomy versus open distal pancreatectomy with at least two to three years of follow-up. Such studies should include patient-oriented outcomes such as short-term mortality and long-term mortality (at least two to three years); health-related quality of life; complications and the sequelae of complications; resection margins; measures of earlier postoperative recovery such as length of hospital stay, time to return to normal activity and time to return to work (in those who are employed); and recurrence of cancer.

Bortezomib for the treatment of multiple myeloma Kathleen Scott, Patrick J Hayden, Andrea Will, Keith Wheatley, Imelda Coyne First published: 20 April 2016 This meta-analysis found that myeloma patients receiving bortezomib benefited in terms of OS, PFS and response rate compared to those who did not receive bortezomib. This benefit was observed in trials of bortezomib versus no bortezomib with the same background therapy and in trials of bortezomib versus no bortezomib with different background therapy in each arm or compared to other agent(s). Further evaluation of newer proteasome inhibitors is required to ascertain whether these agents offer an improved risk-benefit profile, while more studies of HRQoL are also required.

Non-surgical interventions for late rectal problems (proctopathy) of radiotherapy in people who have received radiotherapy to the pelvis Fleur T van de Wetering, Leen Verleye, H. Jervoise N Andreyev, et al First published: 25 April 2016 Although some interventions for late radiation proctopathy look promising (including rectal sucralfate, metronidazole added to an anti-inflammatory regimen, and hyperbaric oxygen therapy), single small studies provide limited evidence. Furthermore, outcomes important to people with cancer, including quality of life (QoL) and long-term effects, were not well recorded. The episodic and variable nature of late radiation proctopathy requires large multi-centre placebocontrolled trials (RCTs) to establish whether treatments are effective. Future studies should address the possibility of associated injury to other gastro-intestinal, urinary, or sexual organs, known as pelvic radiation disease. The interventions, as well as the outcome parameters, should be broader and include those important to people with cancer, such as QoL evaluations.

OTHER EVIDENCE UPDATES/GUIDANCE BACK TO TOP

NICE guidance/evidence:

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Prevention of chemotherapy induced nausea and vomiting in adults: netupitant/palonosetron Netupitant/palonosetron (Akynzeo) is licensed in adults for the prevention of acute and delayed nausea and vomiting associated with highly emetogenic cisplatin-based cancer chemotherapy or moderately emetogenic cancer chemotherapy. Two randomised controlled trials and a doseranging study evaluated the safety and efficacy of netupitant/palonosetron in people having chemotherapy.

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Nivolumab for treating advanced unresectable or metastatic) melanoma

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Improving outcomes in colorectal cancer

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Colorectal cancer: the diagnosis and management of colorectal cancer;

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Ovarian cancer- the recognition and initial management of ovarian cancer Surveillance report Decision matrix

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Lung cancer- the diagnosis and treatment of lung cancer Surveillance report Decision matrix

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Improving outcomes in colorectal cancer and Colorectal cancer: The diagnosis and management of colorectal cancer This Surveillance Report focuses on a summary of selected new evidence relevant to NICE clinical guidelines CSG5 and CG131. The decision matrix includes summaries and references for all new evidence considered.

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

More from UpToDate: A nonanthracycline-containing adjuvant regimen for HER2-positive breast cancer The efficacy and safety of combining trastuzumab with a nonanthracycline-containing chemotherapy regimen was evaluated in the Breast Cancer International Research Group 006 (BCIRG-006) trial of over 3200 women with HER2-positive and node-positive breast cancer or high-risk node-negative disease [1]. A preliminary report of 10-year outcomes suggests that, compared with doxorubicin and cyclophosphamide followed by docetaxel (ACT), both ACT with trastuzumab (ACTH) as well as docetaxel, carboplatin, and trastuzumab (TCH) lead to improved disease-free survival (DFS, 75 and 73 percent, respectively, versus 68 percent for ACT) and overall survival (OS, 86 and 83 percent, respectively, versus 79 percent for ACT). A trend toward improved DFS and OS was seen for ACTH compared with TCH, but ACTH was associated with slightly greater toxicity. These results support our recommendation that TCH is an effective alternative treatment to ACTH as adjuvant therapy for HER2-positive breast cancer. (See "Adjuvant medical therapy for HER2-positive breast cancer", section on 'Non-anthracycline based therapy'.) Denosumab in early breast cancer The anti-RANK-ligand denosumab, used concurrently with adjuvant aromatase inhibitors (AIs), is known to improve bone mineral density (BMD) and reduce the risk of fracture. Data are emerging regarding the potential for denosumab to improve disease-free survival (DFS) in postmenopausal women receiving AIs for breast cancer [2]. The Austrian Breast and Colorectal Cancer Study Group (ABCSG-18) study ABCSG-18 assessed DFS in 3400 postmenopausal women on aromatase inhibitors for hormone receptor-positive breast cancer who were randomly assigned to denosumab or placebo. In preliminary data, at a median follow-up of four years, a trend towards improved DFS was seen in the denosumab group. In subset analyses, benefit from denosumab was observed in women with tumors that were larger than 2 cm, that were both estrogen receptor (ER)-positive and progesterone receptor (PR)-positive, or that had ductal histology. We await final reporting of data from ABCSG-18, as well as the Denosumab as Adjuvant Treatment for Women With High Risk Early Breast Cancer Receiving Neoadjuvant or 19

Adjuvant Therapy (D-CARE) study (NCT01077154), to provide further information regarding potential anti-cancer benefits of this agent. (See "Overview of the use of osteoclast inhibitors in early breast cancer", section on 'Efficacy'.) Screening for ovarian cancer in average risk women The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) is the largest randomized trial evaluating the use of serum testing for CA 125 and transvaginal ultrasound (TVUS) for ovarian cancer screening in average risk women [6]. The trial compared three arms: no screening; screening with annual transvaginal ultrasound; and multimodal screening (MMS, consisting of annual CA 125 testing, followed by TVUS if the CA 125 was abnormal, using an algorithmic guideline). After a median of 11 years, cancers were detected in 0.7 percent of women in the MMS group and 0.6 percent of women in the control and TVUS-only groups. Compared with no screening, MMS detected cancer at an earlier stage and the primary analysis showed a nonsignificant trend toward a 15 percent reduction (95% CI -3 to 30) in mortality from ovarian cancer for MMS. When prevalent ovarian cancer cases were excluded, the mortality reduction with MMS was significant. The results of the UKCTOCS trial are not consistent with results from another randomized trial that did not show decreased mortality with MMS. Based on the available data, it is not clear that the benefits of screening for ovarian cancer outweigh the harms related to the adverse effects associated with false positive findings. UpToDate suggests not screening average risk women for ovarian cancer. (See "Screening for ovarian cancer", section on 'Multimodal screening'.) No survival advantage for palliative gastrectomy For some patients with advanced gastric cancer, palliative gastrectomy has been used to provide rapid symptomatic relief of pain, nausea, bleeding, obstruction, and perforation, as well as a possible survival benefit; studies involving palliative gastrectomy have not controlled for other factors that could influence survival such as systemic chemotherapy. The survival benefit of gastrectomy in patients treated with modern systemic chemotherapy was directly tested in the phase III REGATTA trial, in which 175 patients with advanced gastric cancer and a single noncurable factor confined to the liver, peritoneum, or paraaortic lymph nodes were randomly assigned to chemotherapy alone or chemotherapy preceded by gastrectomy [12]. The trial was closed prematurely after an interim analysis suggested that the primary endpoint, overall survival, was not significantly improved by gastrectomy, and that patients undergoing gastrectomy had a significantly higher incidence of several serious adverse events related to chemotherapy. Routine palliative gastrectomy cannot be justified in these patients. (See "Local palliation for advanced gastric cancer", section on 'Palliative resection'.) 20

Oxaliplatin neurotoxicity not prevented by venlafaxine Previous pilot data suggested that venlafaxine might prevent acute and chronic oxaliplatinrelated neuropathy. However, benefit could not be confirmed in a small randomized trial involving 50 patients who were assigned to receive venlafaxine or placebo while being treated with oxaliplatin-based chemotherapy for colon cancer [13]. Although there was a trend toward benefit for venlafaxine when evaluated by the oxaliplatin-specific neuropathy scale, and by some acute neuropathy measures (eg, discomfort swallowing cold liquids) for the first two oxaliplatin doses, these were outweighed by the lack of any benefit in all other assessments including the CIPN20 sensory subscale, physician-completed NCI-CTCAE scores, or in the cumulative administered dose of oxaliplatin, which was identical in both arms. (See "Prevention and treatment of chemotherapy-induced peripheral neuropathy", section on 'Antidepressants'.) Guidelines for active surveillance for patients with low risk, localized prostate cancer Active surveillance for localized prostate cancer entails observation rather than immediate therapy, with curative-intent treatment deferred pending evidence that the patient is at an increased risk for disease progression. This approach is based upon the prolonged natural history of localized prostate cancer and is an attempt to balance the risks and side effects of overtreatment against the possibility of disease progression and a lost opportunity for cure. The American Society of Clinical Oncology (ASCO) has endorsed the Cancer Care Ontario Guideline, which recommends active surveillance for most patients with low risk (Gleason â&#x2030;¤6), localized prostate cancer [24]. This approach is consistent with UpToDate's recommendations for this patient population. (See "Active surveillance for men with early prostate cancer", section on 'Guidelines'.) Docetaxel chemotherapy plus androgen deprivation therapy (ADT) for metastatic castrationsensitive prostate cancer (February 2016) Publication of the results of the STAMPEDE trial lend further support to our recommendation for systemic treatment of advanced castration-sensitive prostate cancer with a combination of docetaxel plus androgen deprivation therapy (ADT) rather than with ADT alone. Findings from this trial were previously only available in abstract form. The results from the STAMPEDE trial found that the addition of six cycles of docetaxel chemotherapy to ADT significantly improved overall survival compared with ADT alone regardless of the disease burden [25]. For men with metastatic castration-sensitive prostate cancer, this combination is now recommended as the preferred initial treatment for men with both low- and high-volume metastatic disease. (See "Initial systemic therapy for castration sensitive prostate cancer", section on 'STAMPEDE trial'.) 21

Androgen deprivation therapy and venous thromboembolic disease Multiple malignancies, including prostate cancer, are associated with an increased risk of venous thromboembolic disease (deep venous thrombosis or pulmonary embolus). In an observational study from the United Kingdom, the risk of venous thromboembolic disease in men with prostate cancer was significantly increased in men who were receiving androgen deprivation therapy (ADT), compared with those who were not taking ADT; the increased risk was limited to the period during ADT treatment [26]. Confounding variables, related to differences in cancer status rather than use of ADT, may influence this finding. When ADT is used for appropriate indications, the potential benefits of ADT for men with prostate cancer appear to outweigh the possible risks. (See "Side effects of androgen deprivation therapy", section on 'Venous thromboembolism'.) Adjuvant chemotherapy for high-risk urothelial bladder cancer Neoadjuvant chemotherapy prior to radical cystectomy improves overall survival in patients with high-risk bladder cancer. However, multiple randomized trials of adjuvant chemotherapy following radical cystectomy either failed to complete planned accrual or were underpowered to demonstrate a statistically significant improvement in survival. An observational study from the National Cancer Data Base provides support for adjuvant chemotherapy; for patients who did not receive neoadjuvant chemotherapy prior to cystectomy, adjuvant chemotherapy was associated with improved overall survival compared with observation post cystectomy [27]. Thus, adjuvant chemotherapy is an option for those with high-risk urothelial bladder cancer who did not receive neoadjuvant chemotherapy. (See "Adjuvant chemotherapy for muscle invasive urothelial carcinoma of the bladder", section on 'Observational studies'.) Sensitivity of magnetic resonance spectroscopy in IDH-mutant gliomas Mutations in isocitrate dehydrogenase (IDH) result in the accumulation of 2-hydroxyglutarate (2HG) in IDH-mutant gliomas. Small studies have shown that 2HG can be detected noninvasively by magnetic resonance spectroscopy, but the sensitivity of the technique has not been reported. In a study that included 80 biopsy-confirmed IDH mutant tumors, the sensitivity of spectroscopy for detecting 2HG ranged from 8 percent in small tumors (<3.4 mL) to 91 percent in large tumors (>8 mL) [40]. Levels of 2HG did not correlate with tumor grade or mitotic index. (See "Clinical presentation and diagnosis of brain tumors", section on 'Magnetic resonance spectroscopy'.) Pembrolizumab in non-small cell lung cancer

Programmed death-1 (PD-1) receptor blocking antibodies have received approval by the US Food and Drug Administration (FDA) for use in advanced non-small cell lung cancer (NSCLC) that has progressed on other therapies. In the phase II/III KEYNOTE-010 study, over 1000 patients with previously treated advanced NSCLC were randomly assigned to the PD-1 antibody pembrolizumab 2 mg/kg, pembrolizumab 10 mg/kg, or docetaxel [58]. Pembrolizumab at 2 and 10 mg/kg was associated with improved median overall survival in patients with at least 50 percent of tumor cells expressing programmed death-ligand 1 (PD-L1) (14.9 and 17.3 months, respectively, versus 8.2 months for the docetaxel-treated group) and in the overall group of patients (10.4 and 12.7 months, respectively, versus 8.5 months for the docetaxel-treated group). Fewer grade 3 and higher adverse events were noted among patients receiving pembrolizumab. These results support the use of an anti-PD-1 antibody in the treatment of NSCLC after progression on standard chemotherapy. (See "Immunotherapy of non-small cell lung cancer with immune checkpoint inhibition", section on 'Pembrolizumab'.) Minimal residual disease in NPM1-mutated AML Testing for minimal residual disease (MRD) is commonly used to monitor patients with acute promyelocytic leukemia (APL) in complete remission (CR). The value of MRD monitoring in nonAPL acute myeloid leukemia (AML) is less clear. MRD monitoring was assessed in a large study of patients with NPM1-mutated AML treated within a clinical trial [1]. When compared with MRD negative cases, those with detectable MRD at the time of first CR had higher relapse rates and inferior overall survival. Assessment of MRD at other time points did not provide additional prognostic value, nor did the coexistence of mutations usually associated with poor prognosis (eg, FLT3-ITD and DNMT3A). While these results support the prognostic value of MRD in non-APL AML, the use of NPM1 and other markers for MRD testing needs to be confirmed using validated techniques before such results can be used to escalate or de-escalate post-remission therapy. (See "Remission criteria in acute myeloid leukemia and monitoring for residual disease", section on 'Use in non-APL AML'.) Caplacizumab for acquired TTP Thrombotic thrombocytopenic purpura (TTP) is a medical emergency that is almost always fatal without treatment. Even with plasma exchange (PEX), mortality is as high as 10 percent. Caplacizumab is a monoclonal antibody fragment designed to block binding of platelets to the ultralarge multimers of von Willebrand factor (VWF) that form in TTP. In a randomized trial in which 75 patients with acquired TTP received caplacizumab or placebo (all patients received PEX), caplacizumab was associated with a faster time to response, fewer days of PEX, and

greater frequency of remission [52]. This therapy is not yet available outside of a clinical trial. (See "Acquired TTP: Initial treatment", section on 'Anti-VWF (caplacizumab)'.) Glucocorticoid dose in ITP Many adults with immune thrombocytopenia (ITP) do not require treatment. For those who do, glucocorticoids are used, but the optimal dosing has been unclear. A new trial supports our preference for high-dose dexamethasone rather than prednisone for most patients and illustrates differences in side effect profiles. In this trial, 195 adults with newly diagnosed ITP requiring therapy were randomly assigned to receive either oral dexamethasone at 40 mg daily for four days without a taper or oral prednisone at 1 mg/kg daily for four weeks followed by a gradual taper [53]. High-dose dexamethasone was associated with a higher response rate, more rapid responses, and fewer adverse events. Common dexamethasone side effects included insomnia and mood disturbance, while prednisone more often caused dizziness, hypertension, hyperglycemia, and weight gain. (See "Immune thrombocytopenia (ITP) in adults: Initial treatment and prognosis", section on 'Glucocorticoids'.) Bendamustine plus obinutuzumab for follicular lymphoma It is not known whether the novel anti-CD20 monoclonal antibody obinutuzumab is better than rituximab for the treatment of relapsed or refractory follicular lymphoma (FL). Preliminary results are available from a trial in which 321 patients with relapsed or refractory FL were randomly assigned to six cycles of bendamustine alone versus six cycles of bendamustine plus obinutuzumab, followed by obinutuzumab maintenance for two years [27]. The addition of obinutuzumab improved progression-free survival, leading to the approval of this regimen by the US Food and Drug Administration for FL relapsed or refractory after a rituximab-containing regimen. However, we do not routinely use this regimen, as it has not demonstrated an overall survival benefit and requires longer follow-up to better clarify potential long-term toxicities. In addition, it has not been compared directly with rituximab-containing regimens in this setting. (See "Treatment of relapsed or refractory follicular lymphoma", section on 'Chemoimmunotherapy'.)

BMJ Evidence Updates: P53 and SOX2 Protein Expression Predicts Esophageal Adenocarcinoma in Response to Neoadjuvant Chemoradiotherapy. Ann Surg Inferring the Effects of Cancer Treatment: Divergent Results From Early Breast Cancer Trialists` Collaborative Group Meta-Analyses of Randomized Trials and Observational Data From SEER Registries. J Clin Oncol Hospital at home: home-based end-of-life care. Cochrane Database Syst Rev Risk of invasive cervical cancer after atypical glandular cells in cervical screening: nationwide cohort study. BMJ Irinotecan chemotherapy combined with fluoropyrimidines versus irinotecan alone for overall survival and progression-free survival in patients with advanced and/or metastatic colorectal cancer. Cochrane Database Syst Rev Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial. Lancet Compression Stockings for Preventing the Postthrombotic Syndrome in Patients with Deep Vein Thrombosis. Am J Med Vasopressors for hypotensive shock. Cochrane Database Syst Rev Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report. Chest Viscosupplementation for Osteoarthritis of the Knee: A Systematic Review of the Evidence. J Bone Joint Surg Am Effects of Testosterone Treatment in Older Men. N Engl J Med Initial Combination Therapy With Canagliflozin Plus Metformin Versus Each Component as Monotherapy for Drug-Naive Type 2 Diabetes. Diabetes Care Pulsed electromagnetic fields in knee osteoarthritis: a double blind, placebo-controlled, randomized clinical trial. Rheumatology (Oxford) Effects of Nicotine Patch vs Varenicline vs Combination Nicotine Replacement Therapy on Smoking Cessation at 26 Weeks: A Randomized Clinical Trial. JAMA Effect of Intensive Versus Usual Blood Pressure Control on Kidney Function Among Individuals With 25

Prior Lacunar Stroke: A Post Hoc Analysis of the Secondary Prevention of Small Subcortical Strokes (SPS3) Randomized Trial. Circulation Periodontal therapy as adjunctive treatment for gastric Helicobacter pylori infection. Cochrane Database Syst Rev Detection of Occult Micrometastases in Patients With Clinical Stage I Non-Small-Cell Lung Cancer: A Prospective Analysis of Mature Results of CALGB 9761 (Alliance). J Clin Oncol Cediranib in patients with relapsed platinum-sensitive ovarian cancer (ICON6): a randomised, double-blind, placebo-controlled phase 3 trial. Lancet Anamorelin in patients with non-small-cell lung cancer and cachexia (ROMANA 1 and ROMANA 2): results from two randomised, double-blind, phase 3 trials. Lancet Oncol A Randomized, Open-Label, Multicenter, Phase III Study of Epoetin Alfa Versus Best Standard of Care in Anemic Patients With Metastatic Breast Cancer Receiving Standard Chemotherapy. J Clin Oncol Nab-paclitaxel versus solvent-based paclitaxel in neoadjuvant chemotherapy for early breast cancer (GeparSepto-GBG 69): a randomised, phase 3 trial. Lancet Oncol Everolimus versus sunitinib for patients with metastatic non-clear cell renal cell carcinoma (ASPEN): a multicentre, open-label, randomised phase 2 trial. Lancet Oncol Thromboprophylaxis in multiple myeloma patients treated with lenalidomide - A systematic review. Thromb Res When are breast cancer patients at highest risk of venous thromboembolism? A cohort study using English health care data. Blood Neratinib after trastuzumab-based adjuvant therapy in patients with HER2-positive breast cancer (ExteNET): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol Determinants of Early Mortality Among 37,568 Patients With Colon Cancer Who Participated in 25 Clinical Trials From the Adjuvant Colon Cancer Endpoints Database. J Clin Oncol Melphalan, prednisone, and lenalidomide versus melphalan, prednisone, and thalidomide in untreated multiple myeloma. Blood Weekly vs. Every-3-Week Paclitaxel and Carboplatin for Ovarian Cancer. N Engl J Med A prognostic index for natural killer cell lymphoma after non-anthracycline-based treatment: a multicentre, retrospective analysis. 26

Lancet Oncol Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction. J Clin Oncol PROCLAIM: Randomized Phase III Trial of Pemetrexed-Cisplatin or Etoposide-Cisplatin Plus Thoracic Radiation Therapy Followed by Consolidation Chemotherapy in Locally Advanced Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol The effectiveness and cost-effectiveness of erythropoiesis-stimulating agents (epoetin and darbepoetin) for treating cancer treatment-induced anaemia (including review of technology appraisal no. 142): a systematic review and economic model. Health Technol Assess Randomized Trial of Hepatic Artery Embolization for Hepatocellular Carcinoma Using DoxorubicinEluting Microspheres Compared With Embolization With Microspheres Alone. J Clin Oncol Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses. BMJ Macrolide antibiotics and the risk of ventricular arrhythmia in older adults. CMAJ Vaccines for preventing herpes zoster in older adults. Cochrane Database Syst Rev Metformin in severe exacerbations of chronic obstructive pulmonary disease: a randomised controlled trial. Thorax Oral fluoroquinolone use and serious arrhythmia: bi-national cohort study. BMJ The Effects of Alternative Resuscitation Strategies on Acute Kidney Injury in Patients with Septic Shock. Am J Respir Crit Care Med Endovascular thrombectomy after large-vessel ischaemic stroke: a meta-analysis of individual patient data from five randomised trials. Lancet Oral Prednisolone in the Treatment of Acute Gout: A Pragmatic, Multicenter, Double-Blind, Randomized Trial. Ann Intern Med The ABC (age, biomarkers, clinical history) stroke risk score: a biomarker-based risk score for predicting stroke in atrial fibrillation. Eur Heart J Randomized Trial of Introduction of Allergenic Foods in Breast-Fed Infants. N Engl J Med 27

Results of a Randomised Controlled Trial Comparing Intravesical Chemohyperthermia with Mitomycin C Versus Bacillus Calmette-Guerin for Adjuvant Treatment of Patients with Intermediateand High-risk Non-Muscle-invasive Bladder Cancer. Eur Urol Afatinib plus vinorelbine versus trastuzumab plus vinorelbine in patients with HER2-overexpressing metastatic breast cancer who had progressed on one previous trastuzumab treatment (LUX-Breast 1): an open-label, randomised, phase 3 trial. Lancet Oncol Final Results of the Sunbelt Melanoma Trial: A Multi-Institutional Prospective Randomized Phase III Study Evaluating the Role of Adjuvant High-Dose Interferon Alfa-2b and Completion Lymph Node Dissection for Patients Staged by Sentinel Lymph Node Biopsy. J Clin Oncol Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial. Lancet Impact of Patient Factors on Recurrence Risk and Time Dependency of Oxaliplatin Benefit in Patients With Colon Cancer: Analysis From Modern-Era Adjuvant Studies in the Adjuvant Colon Cancer End Points (ACCENT) Database. J Clin Oncol Antifibrinolytics (lysine analogues) for the prevention of bleeding in people with haematological disorders. Cochrane Database Syst Rev Intraoperative frozen section analysis for the diagnosis of early stage ovarian cancer in suspicious pelvic masses. Cochrane Database Syst Rev Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Lancet Oncol Clinical features of large cell neuroendocrine carcinoma: a population-based overview. Eur Respir J Effects of Long-Term Low-Molecular-Weight Heparin on Fractures and Bone Density in Non-Pregnant Adults: A Systematic Review With Meta-Analysis. J Gen Intern Med Different dosage schedules for reducing cardiotoxicity in people with cancer receiving anthracycline chemotherapy. Cochrane Database Syst Rev Predictive Value of Six Prognostic Scoring Systems for Spinal Bone Metastases: An Analysis Based on 1379 Patients. Spine (Phila Pa 1976) Enzalutamide Versus Bicalutamide in Castration-Resistant Prostate Cancer: The STRIVE Trial. J Clin Oncol 28

SIRFLOX: Randomized Phase III Trial Comparing First-Line mFOLFOX6 (Plus or Minus Bevacizumab) Versus mFOLFOX6 (Plus or Minus Bevacizumab) Plus Selective Internal Radiation Therapy in Patients With Metastatic Colorectal Cancer. J Clin Oncol Effect of Sulindac and Erlotinib vs Placebo on Duodenal Neoplasia in Familial Adenomatous Polyposis: A Randomized Clinical Trial. JAMA A Risk-Scoring System Combined With a Fecal Immunochemical Test Is Effective in Screening HighRisk Subjects for Early Colonoscopy to Detect Advanced Colorectal Neoplasms. Gastroenterology Opioids for the palliation of refractory breathlessness in adults with advanced disease and terminal illness. Cochrane Database Syst Rev Lenalidomide versus investigator`s choice in relapsed or refractory mantle cell lymphoma (MCL-002; SPRINT): a phase 2, randomised, multicentre trial. Lancet Oncol Efficacy and safety of fosaprepitant for the prevention of nausea and emesis during 5 weeks of chemoradiotherapy for cervical cancer (the GAND-emesis study): a multinational, randomised, placebo-controlled, double-blind, phase 3 trial. Lancet Oncol Radiation plus Procarbazine, CCNU, and Vincristine in Low-Grade Glioma. N Engl J Med Blood-Pressure and Cholesterol Lowering in Persons without Cardiovascular Disease. N Engl J Med Blood-Pressure Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med A Multicenter Observational Study of Incretin-based Drugs and Heart Failure. N Engl J Med Effectiveness of non-steroidal anti-inflammatory drugs for the treatment of pain in knee and hip osteoarthritis: a network meta-analysis. Lancet Aspirin for the Prevention of Cancer Incidence and Mortality: Systematic Evidence Reviews for the U.S. Preventive Services Task Force. Ann Intern Med Cholesterol Lowering in Intermediate-Risk Persons without Cardiovascular Disease. N Engl J Med Antipsychotic Medication for Prevention and Treatment of Delirium in Hospitalized Adults: A Systematic Review and Meta-Analysis. J Am Geriatr Soc CURB-65 Performance among Admitted and Discharged Emergency Department Patients with Community Acquired Pneumonia. 29

Acad Emerg Med Antidepressant use and risk of cardiovascular outcomes in people aged 20 to 64: cohort study using primary care database. BMJ Metformin for chemoprevention of metachronous colorectal adenoma or polyps in postpolypectomy patients without diabetes: a multicentre double-blind, placebo-controlled, randomised phase 3 trial. Lancet Oncol

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CANCER IN THE NEWS BACK TO TOP

Leukaemia therapy retrains immune system Scientists in the US are excited by a new cancer treatment that has reportedly sent terminally ill leukaemia patients into remission. The therapy involves taking T-cells from the patient’s immune system and modifying them to target leukaemia cells. Over 90 percent of patients in the study were sent into complete remission. However, other participants became ill enough to require intensive care and two patients died. The treatment has been described as a 'paradigm shift' but so far has only been shown to work in those rare patients who have not responded to standard treatments for blood cancer.

New immunotherapy discovery could give treatments the precision they need Over the past few years, immunotherapies – treatments which harness the power of the immune system to fight cancer – have been making headlines around the world. These powerful new weapons are exciting because once the immune system has ‘locked-on’ to a cancer cell it’s persistent and ruthless in taking it out. For patients in whom they work, immunotherapies can produce long-lasting effects. Some have even suggested they can cure certain cancers. But the biggest challenges for immunotherapy have been identifying which molecules on the cancer cells are the best targets, as well as how to get past cancer’s defences. For now, the immunotherapy treatments available to patients are powerful-but-blunt weapons, which in some cases can result in a number of potentially serious side effects. What’s urgently needed are treatments that can guide immune cells to specifically attack a tumour, while leaving healthy cells alone. And today, Cancer Research UK scientists have published a new study in the journal Science that may have uncovered the intelligence needed to precisely guide these new weapons.

Be Clear on Cancer: ‘blood in pee’ campaign Public Health England has launched a national Be Clear on Cancer campaign to highlight blood in pee as a key symptom for bladder and kidney cancers. The campaign is aimed at men and women aged 50 and over, as between 90 to 97% of bladder and kidney cancer diagnoses are in people in this age group. It encourages anyone who notices blood in their pee, even if it’s ‘just the once’, to visit their GP to get it checked out. Given that people may not spot blood in their pee unless they check, this year’s campaign also promotes a ‘look before you flush’ message, particularly to women, who may be less likely to do so.

Cancer ‘master control switch’ could help tumours hide from immune system US and German scientists have found (link is external) a crucial link between a gene often found to be overactive in cancer cells, and tumours’ ability to hide from the immune system. The discovery, in

studies on mice, highlights the growing importance of treatments that activate patients’ immune system – so-called immunotherapies. Experts hope the “exciting” findings may help pave the way for new treatments to be developed.

High white blood cell ratio linked to recurrence risk in early stage breast cancer A high ratio of two types of immune system cell is linked to an increased risk of disease recurrence after a diagnosis of early stage breast cancer, finds the first study of its kind, published on the eve of international Women’s Day (March 8) in the online journal ESMO Open. The finding might guide future treatment and monitoring strategies, if prospective studies confirm the link, say the researchers.

Other news… 

Researchers discover pancreatic cancer is 'four different diseases'

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Blood analysis could offer a real-time ‘snapshot’ of melanoma treatment

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HIV drug could stop skin cancer becoming drug-resistant

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Ejaculate More, Have Less Prostate Cancer Risk

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Test could spare breast cancer patients unnecessary chemotherapy

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Studies show continued promise for immunotherapy drugs

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Immunotherapy and chemo combination shows early promise for pancreatic cancer

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Prostate cancer drug approved for routine use before chemotherapy

REPORTS, PUBLICATIONS AND RESOURCES

End of life care and physician assisted dying The British Medical Association has published End-of-life care and physician-assisted dying: reflections and recommendations. This is the final part of a three volume report of a project covering both end-of-life care and physician-assisted dying. The purpose of this volume is to reflect on some of the points emerging from the public dialogue research and what lessons can be learnt and what changes are needed to ensure that doctors are able to provide high quality end-of-life care for all of their patients. It sets the agenda for future work and policy development in this area.

NICE updates guidelines information to put patients at centre of decision making. NICE has updated its guidelines pages to explain how they should be used in offering patients and service users the best care. The new wording explains that guidelines should be taken fully into account but that the patient, or person receiving care, should be at the heart of decision-making.

Cancer Nursing Partnership The CNP was officially launched on 15 September 2014 and is a unique partnership made up of 11 organisations, representing tens of thousands of nurses, which aims to support improvements in cancer care. Our immediate focus is on delivering the Recovery Package. Each month a Bulletin will be issued to keep our members informed of key developments, innovations and services aiming to be a source of support. Please find the link to the inaugural issue below.

Implementing the Cancer Taskforce Recommendations: Commissioning person centred care for people affected by cancer NHS England, April 2016 This guidance is intended to support commissioners and strategic clinical networks to ensure every person affected by cancer will have access to the Recovery Package and *stratified followup pathways by 2020, as set out in the cancer strategy. It describes the actions you will need to take to deliver this including checklists for developing service specifications, practical examples and templates to use and adapt locally. When developing and implementing these interventions, commissioners should also take into account the duties placed on them under the Equality Act 2010 and with regard to reducing health inequalities, duties under the Health and Social Care Act 2012. Service design and communications should be appropriate and accessible to meet the needs of diverse communities. Guidance for NHS commissioners on Equality and Health Inequalities Legal Duties is also available.

TRAINING & NETWORKING OPPORTUNITIES, CONFERENCES, EVENTS BACK TO TOP

EONS 10: early-bird registration now open Register for the EONS 10 congress before 30 July 2016 to get a discount on the regular booking rate. This congress is a chance to meet other cancer nurses from all over Europe and get up to date on the latest developments in the field. We are delighted that this year our congress will be held jointly with the 18th International Psycho-Oncology Society (IPOS) Congress. + Find out more

20 May 2016 | Dublin, Ireland 4th Beacon Hospital International Stereotactic Radiosurgery and Stereotactic Ablative Radiotherapy Symposium More information: www.beaconhospital.ie/symposium2016 3 June 2016 | Barcelona, Spain Integration of new technologies in the clinical practice in radiation oncology 18 - 19 June 2016 | Ann Arbor, MI, USA 4th MR in RT event More information: www.med.umich.edu/radonc/MRinRT2016 27 - 29 June 2016 | San Francisco, USA 6th World Congress of Brachytherapy More information: www.estro.org/congresses-meetings/items/wcb-2016

Brachytherapy for prostate cancer 5-7 June 2016 / Brussels, Belgium; Early rate deadline: 7 March 2016 Clinical practice and implementation of image-guided stereotactic body radiotherapy 5-9 June 2016 / Athens, Greece Early rate deadline: 7 March 2016 Evidence based radiation oncology - how to evaluate the scientific evidence and apply it to daily practice 12-17 June 2016 / Porto, Portugal Early rate deadline: 14 March 2016 Advanced skills in modern radiotherapy 19-23 June 2016 / Dublin, Ireland Early rate deadline: 21 March y 2016 Multidisciplinary management of lung cancer 26-28 June 2016 / Moscow, Russia Early rate deadline: 28 March 2016

Multidisciplinary management of head and neck oncology 26-29 June 2016 / Florence, Italy Early rate deadline: 28 March 2016

ESNM/ESTRO course on molecular imaging and radiation oncology 19-22 May 2016 / Lisbon, Portugal Lower GI: technical and clinical challenges for radiation oncologists 22-27 May 2016 / Brussels, Belgium Upper GI: technical and clinical challenges for radiation oncologists 28-31 May 2016 / Brussels, Belgium Advanced brachytherapy physics 29 May â&#x20AC;&#x201C; 1 June 2016 / Vienna, Austria 11/5 20th Training Course in Haematopoietic Stem Cell Transplantation 11 - 14 May 2015 in Budapest, Hungary + Info 24/5 4th EBMT Statistical Course 2016 24 - 27 May 2016 in Leiden, The Netherlands + Info 26/5 10th Meeting of the EBMT Paediatric Disease Working Party and 5th Meeting of the EBMT Paediatric Nurses 26 - 28 May 2016 in Island of Rhodes, Greece + Info

Via ESTRO: ESNM/ESTRO course on molecular imaging and radiation oncology 19-22 May 2016 / Lisbon, Portugal Lower GI: technical and clinical challenges for radiation oncologists 25-27 May 2016 / Brussels, Belgium Upper GI: technical and clinical challenges for radiation oncologists 28-31 May / Brussels, Belgium Brachytherapy for prostate cancer 5-7 June 2016 / Brussels, Belgium Evidence based radiation oncology - how to evaluate the scientific evidence and apply it to daily practice 12-17 June / Porto, Portugal Advanced skills in modern radiotherapy 19-23 June 2016 / Dublin, Ireland Multidisciplinary management of lung cancer 26-28 June 2016 / Moscow, Russia Multidisciplinary management of head and neck oncology 26-29 June 2016 / Florence, Italy

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. C. Alerts One of the services offered by the Clinical Librarian is personsalised literature/evidence alerts. All you need to do is identify which ongoing evidence issues you are particularly interested in and provide that information to Terence.Harrison@tst.nhs.uk Once something comes up that matches those interests you will then be emailed the details.

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