July 16 cancer current awareness2

Clinical Librarian Service Musgrove Park Academy

Current Awareness

Cancer Issue 7 July 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

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Contents Click on a section title to navigate to contents

Page Recent journal articles

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New books

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Cochrane Reviews

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Other evidence updates

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Cancer in the News

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Reports, publications and resources

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Training & Networking Opportunities, Conferences, Events

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Other services, Training and Athens

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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

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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 New therapy for acute lymphoblastic leukaemia Emma Wilkinson Published Online: 16 June 2016 Inotuzumab ozogamicin (a monoclonal antibody-drug conjugate) significantly increased the number of patients with refractory or relapsed acute lymphoblastic leukaemia (ALL) achieving complete remission and also significantly prolonged overall survival, a new trial suggests. The conjugate combines an anti-CD22 antibody—enabling the direct targeting of B cells—with cytotoxic drug calicheamicin.

Renal Complications of Hematopoietic-Cell Transplantation N Engl J Med 2016; 374:2256-2267June 9, 2016 Despite overall improvement in the outcomes of hematopoietic-cell transplantation, kidney injury is a frequent complication. The author reviews the causes, diagnosis, and management of renal complications and disorders after hematopoietic-cell transplantation.

Genomic Classification and Prognosis in Acute Myeloid Leukemia N Engl J Med 2016; 374:2209-2221June 9 The driver landscape in AML reveals distinct molecular subgroups that reflect discrete paths in the evolution of AML, informing disease classification and prognostic stratification

Rare disruptive mutations and their contribution to the heritable risk of colorectal cancer Nature Communications 7,Article number: 11883doi:10.1038/ncomms11883Received 21 January 2016 Accepted 09 May 2016 Published 22 June 2016 Colorectal cancer (CRC) displays a complex pattern of inheritance. It is postulated that much of the missing heritability of CRC is enshrined in high-impact rare alleles, which are mechanistically and clinically important. In this study, we assay the impact of rare germline mutations on CRC, analysing 3

high-coverage exome sequencing data on 1,006 early-onset familial CRC cases and 1,609 healthy controls, with additional sequencing and array data on up to 5,552 cases and 6,792 controls. We identify highly penetrant rare mutations in 16% of familial CRC. Although the majority of these reside in known genes, we identify POT1, POLE2 and MRE11 as candidate CRC genes. We did not identify any coding low-frequency alleles (1–5%) with moderate effect. Our study clarifies the genetic architecture of CRC and probably discounts the existence of further major high-penetrance susceptibility genes, which individually account for >1% of the familial risk. Our results inform future study design and provide a resource for contextualizing the impact of new CRC genes.

10 year survival after breast-conserving surgery plus radiotherapy compared with mastectomy in early breast cancer in the Netherlands: a population-based study Marissa C van Maaren et al The Lancet, Published Online: 22 June 2016 Adjusting for confounding variables, breast-conserving surgery plus radiotherapy showed improved 10 year overall and relative survival compared with mastectomy in early breast cancer, but 10 year distant metastasis-free survival was improved with breast-conserving surgery plus radiotherapy compared with mastectomy in the T1N0 subgroup only, indicating a possible role of confounding by severity. These results suggest that breast-conserving surgery plus radiotherapy is at least equivalent to mastectomy with respect to overall survival and may influence treatment decision making for patients with early breast cancer.

Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy Kranz LM, Diken M, Haas H, et al.

Nature. Published online June 1 2016 Lymphoid organs, in which antigen presenting cells (APCs) are in close proximity to T cells, are the ideal microenvironment for efficient priming and amplification of T-cell responses1. However, the systemic delivery of vaccine antigens into dendritic cells (DCs) is hampered by various technical challenges. Here we show that DCs can be targeted precisely and effectively in vivo using intravenously administered RNA-lipoplexes (RNA-LPX) based on well-known lipid carriers by optimally adjusting net charge, without the need for functionalization of particles with molecular ligands. The LPX protects RNA from extracellular ribonucleases and mediates its efficient uptake and expression of the encoded antigen by DC populations and macrophages in various lymphoid compartments. RNA-LPX triggers interferon-α (IFNα) release by plasmacytoid DCs and macrophages.

Consequently, DC maturation in situ and inflammatory immune mechanisms reminiscent of those in the early systemic phase of viral infection are activated2. We show that RNA-LPX encoding viral or mutant neo-antigens or endogenous self-antigens induce strong effector and memory T-cell responses, and mediate potent IFNα-dependent rejection of progressive tumours. A phase I dose4

escalation trial testing RNA-LPX that encode shared tumour antigens is ongoing. In the first three melanoma patients treated at a low-dose level, IFNα and strong antigen-specific T-cell responses were induced, supporting the identified mode of action and potency. As any polypeptide-based antigen can be encoded as RNA3, 4, RNA-LPX represent a universally applicable vaccine class for systemic DC targeting and synchronized induction of both highly potent adaptive as well as type-IIFN-mediated innate immune mechanisms for cancer immunotherapy.

Cholesterol biosynthesis pathway as a novel mechanism of resistance to estrogen deprivation in estrogen receptor-positive breast cancer.

Simigdala N, Gao Q, Pancholi S, Roberg-Larsen H, et al.

Breast Cancer Research. Published online June 1 2016

Combined IL-21–primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient.

Chapuis AG, Lee SM, Thompson JA, et al.

Journal of Experimental Medicine. Published online May 30 2016 Adoptive transfer of peripheral blood–derived, melanoma-reactive CD8+ cytotoxic T lymphocytes (CTLs) alone is generally insufficient to eliminate bulky tumors. Similarly, monotherapy with antiCTLA4 infrequently yields sustained remissions in patients with metastatic melanoma. We postulated that a bolus of enhanced IL-21–primed polyclonal antigen-specific CTL combined with CTLA4 blockade might boost antitumor efficacy. In this first-in-human case study, the combination successfully led to a durable complete remission (CR) in a patient whose disease was refractory to both monoclonal CTL and anti-CTLA4. Long-term persistence and sustained anti-tumor activity of transferred CTL, as well as responses to nontargeted antigens, confirmed mutually beneficial effects of the combined treatment. In this first-in-human study, Chapuis et al. demonstrate that the combination of adoptive cellular therapy with CTLA4 blockade induces long-term remission in a melanoma patient resistant to both modalities administered serially and individually

Phase II Study of Autologous Monocyte-Derived mRNA Electroporated Dendritic Cells (TriMixDCMEL) Plus Ipilimumab in Patients With Pretreated Advanced Melanoma Sofie Wilgenhof, Jurgen Corthals, Carlo Heirman, Nicolas van Baren, Sophie Lucas, Pia Kvistborg, Kris Thielemans and Bart Neyns JCO April 20, 2016 vol. 34 no. 12 1330-1338 The 6-month disease control rate was 51% (95% CI, 36% to 67%), and the overall tumor response rate was 38% (including eight complete and seven partial responses). Seven complete 5

responses and one partial tumor response are ongoing after a median follow-up time of 36 months (range, 22 to 43 months). The most common treatment-related adverse events (all grades) consisted of local DC injection site skin reactions (100%), transient post–DC infusion chills (38%) and flu-like symptoms (84%), dermatitis (64%), hepatitis (13%), hypophysitis (15%), and diarrhea/colitis (15%). Grade 3 or 4 immune-related adverse events occurred in 36% of patients. There was no grade 5 adverse event. The combination of TriMixDC-MEL and ipilimumab is tolerable and results in an encouraging rate of highly durable tumor responses in patients with pretreated advanced melanoma.

Miscellaneous Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial Lancet Oncol; 2016 May 27; EPub Ahead of Print; TY Seiwert, B Burtness, R Mehra, et al Pembrolizumab was well tolerated and demonstrated clinically meaningful antitumour activity in recurrent or metastatic squamous cell carcinoma of the head and neck, supporting further study of pembrolizumab as anticancer therapy for advanced head and neck cancers.

Prognostic Impact of the Combination of Recurrence Score and Quantitative Estrogen Receptor Expression (ESR1) on Predicting Late Distant Recurrence Risk in Estrogen Receptor–Positive Breast Cancer After 5 Years of Tamoxifen: Results From NRG Oncology/National Surgical Adjuvant Breast and Bowel Project B-28 and B-14 J. Clin. Oncol; 2016 May 23; EPub Ahead of Print; N Wolmark, EP Mamounas, FL Baehner, et al For LDR, RS is strongly prognostic in patients with higher quantitative ESR1. Risk of LDR is relatively low for patients with low RS. These results suggest the value of extended tamoxifen therapy merits evaluation in patients with intermediate and high RS with higher ESR1 expression at initial diagnosis

Association Between Complementary and Alternative Medicine Use and Breast Cancer Chemotherapy Initiation: : The Breast Cancer Quality of Care (BQUAL) Study JAMA Oncol; 2016 May 12; EPub Ahead of Print; H Greenlee, AI Neugut, L Falci, et al CAM use was high among patients with early-stage breast cancer enrolled in a multisite prospective cohort study. Current dietary supplement use and higher number of CAM modalities used but not mind-body practices were associated with decreased initiation of clinically indicated chemotherapy.

Oncologists should consider discussing CAM with their patients during the chemotherapy decisionmaking process.

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Exercise and Risk of Cardiovascular Events in Women With Nonmetastatic Breast Cancer JCO May 23, 2016 JCO656603 Exercise is associated with substantial, graded reductions in the incidence of cardiovascular events in women with nonmetastatic breast cancer.

Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years June 5, 2016DOI: 10.1056/NEJMoa1604700 The extension of treatment with an adjuvant aromatase inhibitor to 10 years resulted in significantly higher rates of disease-free survival and a lower incidence of contralateral breast cancer than those with placebo, but the rate of overall survival was not higher with the aromatase inhibitor than with placebo.

Plasma ESR1 Mutations and the Treatment of Estrogen Receptor–Positive Advanced Breast Cancer JCO June 6, 2016 JCO673061

ESR1 mutation analysis in plasma after progression after prior AI therapy may help direct choice of further endocrine-based therapy. Additional confirmatory studies are required.

Nurse-led clinic for men receiving targeted therapies for metastatic hormone-relapsed prostate cancer Sarah Jones et al Cancer Nursing Practice 2016 15 (5) p32-36

Rituximab and dose-dense chemotherapy for adults with Burkitt’s lymphoma: a randomised, controlled, open-label, phase 3 trial Vincent Ribrag et al Lancet 2016 387 (10036) p2402-2411

Development and implementation of nursing grand rounds in a cancer centre Rachel Haigh et al Cancer Nursing Practice 2016 15 (5) p24-30 7

A. In brief (you may need to logon to BMJ to see): Breast cancer Statins could be new treatment option in women with oestrogen receptor positive breast cancer Zosia Kmietowicz Extra five years of aromatase inhibitors increases disease-free survival in breast cancer Ingrid Torjesen Gene profiling should be offered to some patients with breast cancer, says NICE Jacqui Wise "Take two"? The role of second opinions for breast biopsy specimens Rohit Bhargava, Nancy E Davidson External validation of clinical prediction models using big datasets from e-health records or IPD meta-analysis: opportunities and challenges Richard D Riley, Joie Ensor, Kym I E Snell, Thomas P A Debray, Doug G Altman, Karel G M Moons, Gary S Collins Evaluation of 12 strategies for obtaining second opinions to improve interpretation of breast histopathology: simulation study Joann G Elmore, Anna NA Tosteson, Margaret S Pepe, Gary M Longton, Heidi D Nelson, Berta Geller, Patricia A Carney, Tracy Onega, Kimberly H Allison, Sara L Jackson, Donald L Weaver 10-Minute Consultation: Acute painful breast in a non-lactating woman Jessamy Bagenal, Janani Bodhinayake, Kathryn E Williams Lung cancer (oncology) Deaths caused by lung disease have not decreased over past decade, shows UK study Jacqui Wise Prostate cancer Collaboration and patient centred care David Payne NICE backs laser treatment for men with enlarged prostate Jacqui Wise Screening (oncology) Collaboration and patient centred care David Payne Evaluation of 12 strategies for obtaining second opinions to improve interpretation of breast histopathology: simulation study Joann G Elmore, Anna NA Tosteson, Margaret S Pepe, Gary M Longton, Heidi D Nelson, Berta Geller, Patricia A Carney, Tracy Onega, Kimberly H Allison, Sara L Jackson, Donald L Weaver Pioglitazone seems safe and effective for patients with fatty liver disease and diabetes Jacqui Wise Cuts in health prevention budgets will hit the NHS, says NHS England chief Matthew Limb Case Review: A link between asthenia, pallor, and jaundice JoĂŁo Tavares, Gisela EugĂŠnio, Suzana Calretas, Rui Silva, Rui Santos, Armando Carvalho Chemotherapy Glucocorticoids may increase risk of serious blood infection Jacqui Wise

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For automated tables of contents: Oncology – click here Haematology – click here.

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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.

Multiple choice questions for haematology and core medical trainees (2016) Bain, Barbara J. Written to help haematology and general medical trainees evaluate their own knowledge, and particularly useful for those preparing for the Part 1 examination of the Royal College of Pathologists.

BMJ easily missed? : cancer, inflammation and infection (2016) Harnden, Anthony; Lehman, Richard This book groups together a series of useful articles on cancer diagnoses that may be easily missed at first presentation in primary care together with other articles on the early diagnosis of important infections and inflammatory conditions. The spectrum of conditions ranges from colorectal, lung, ovarian and pancreatic cancers to primary HIV infection, infective endocarditis, giant cell arteritis and appendicitis

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COCHRANE REVIEWS/UPDATES BACK TO TOP

Sipuleucel-T for metastatic castration-resistant prostate cancer Steven E Canfield , Vishnukamal Golla , Lillian S Kao , Greg Pratt , Cara Foldes and Philipp Dahm

Debulking hysterectomy followed by chemoradiotherapy versus chemoradiotherapy for FIGO stage IB2/II cervical cancer Manas Chakrabarti and Andy Nordin

Chemoprevention agents for prostate cancer Phillip M Zegelbone , Tea Reljic , Danyell Wilson , Rahul Mhaskar , Branko Miladinovic , Ambuj Kumar and Benjamin Djulbegovic

First-line chemotherapy in low-risk gestational trophoblastic neoplasia Theresa A Lawrie , Mo'iad Alazzam , John Tidy , Barry W Hancock and Raymond Osborne

Massage with or without aromatherapy for symptom relief in people with cancer Ein-Soon Shin , Kyung-Hwa Seo , Sun-Hee Lee , Ji-Eun Jang , Yu-Min Jung , Min-Ji Kim and JiYun Yeon

Ghrelin for the management of cachexia associated with cancer Mahalaqua Nazli Khatib , Anuraj Shankar , Richard Kirubakaran , Abhay Gaidhane , Shilpa Gaidhane , Padam Simkhada and Zahiruddin Quazi Syed

Transabdominal ultrasound or endoscopic ultrasound for diagnosis of gallbladder polyps Sarah Z Wennmacker, Mark P Lamberts, Joost PH Drenth, Kurinchi Selvan Gurusamy, Cornelis JHM van Laarhoven

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High dose, high risk? What updated evidence tells us about chemotherapy dosing in early breast cancer Annabel Goodwin, Melina Willson, Nicholas Wilcken Cochrane Editorial In the 1990s, chemotherapy was established as an effective therapy for early breast cancer, reducing recurrence rates and improving survival. Therefore, it was postulated that higher doses of treatment might be more effective. Indeed, uncontrolled studies of highly selected patients suggested that better rates of survival were achieved by giving doses of chemotherapy so high that bone marrow transplant or other forms of stem cell support were required. There was even a time when the commonest indication for bone marrow transplant in the USA was not leukaemia (where it cures disease) but breast cancer. However, randomized trials were initiated, and we now have an updated systematic review of these trials with mature follow-up.

This review has been updated with new data in the form of extended follow-up from the existing trials. The answer we have now could not be more definitive: there is high-quality evidence that high-dose chemotherapy does not improve survival in breast cancer. The effect sizes are remarkably consistent, the results statistically secure, and follow-up is now available for up to 12 years post-randomization. Increased doses of chemotherapy also carry an increased risk of toxicity, including treatment-related deaths: a lose-lose situation.

How did we come to believe that high-dose chemotherapy might work in the first place, and how can we explain why it doesn’t? The answer to the initial question is human nature. We wanted it to work; there were some preclinical data, and the early 'trials' we had suggested a very good outcome with a high-tech glamorous treatment. However, we simply failed to do due diligence. By definition, women fit enough to undergo high-dose treatment and bone marrow transplantation were very fit and likely to fare better in comparison to historical controls. It transpired that our optimism was based on results that proved too good to be true. Two of those early randomized trials were found to be fabrications of a fraudulent study investigator.

The reasons why this approach doesn’t work must remain speculative. Presumably there is a proportion of cancer cells that remain intrinsically chemo-resistant no matter what the dose is.

Additionally, the drugs traditionally used to achieve ablation of the bone marrow (cisplatin, carmustine, thiotepa, etoposide) are not frontline breast cancer drugs. Lastly these trials were done in an era before we understood how subtype-specific breast cancer can be: breast cancers that are sensitive to endocrine therapy or anti-HER2 therapy are lumped in together with tumours that lack hormone and other receptor overexpression. There may indeed be a subtype of breast cancer that is somewhat dose-sensitive, although it seems unlikely that bone marrow ablation would be required.

The review conclusions are definitive, and we believe that the review question can now effectively be closed off. More recent reviews have opened up potential for other therapeutic approaches. In contrast to the high-dose approach, real and valuable progress has been made over the last two decades with the better-defined use of endocrine therapy, the use of taxane chemotherapy, and the use of anti-HER2 therapy . Taken together the message for us in treating breast cancer seems clear: get smarter, not tougher.

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OTHER EVIDENCE UPDATES/GUIDANCE BACK TO TOP

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

More from UpToDate: Inotuzumab ozogamicin in acute lymphoblastic leukemia (June 2016) Inotuzumab ozogamicin is an investigational anti-CD22 monoclonal antibody conjugated to calicheamicin; it has demonstrated activity in relapsed/refractory acute lymphoblastic leukemia (ALL). Early results are available from an international open-label, randomized phase 3 trial that compared inotuzumab ozogamicin versus intensive chemotherapy in 326 patients with relapsed/refractory ALL [1]. Inotuzumab ozogamicin resulted in a higher percentage of patients achieving a complete response (81 versus 29 percent), many of whom attained minimal residual disease negativity. There was a small improvement in median progression-free survival (five versus two months) and overall survival (eight versus seven months). Inotuzumab ozogamicin results in high rates of deep response in this setting, but the majority of patients will relapse if no further therapy is given. Further study is necessary to better elucidate the best way to incorporate this drug into the treatment of patients with ALL. (See "Treatment of relapsed or refractory acute lymphoblastic leukemia in adults", section on 'Inotuzumab ozogamicin'.)

Virus-specific T cell infusions for patients with primary immunodeficiencies and hematopoietic cell transplant (June 2016) Viral infections, particularly with cytomegalovirus, Epstein-Barr virus, and adenovirus, are a leading cause of death in patients with severe combined immunodeficiency (SCID) and other forms of moderate-to-severe primary immunodeficiency (PID), both before and after hematopoietic cell transplantation (HCT). Investigational infusions of virus-specific T cells (VST) from either stem cell donors or third-party donors have been evaluated to treat and/or prevent these life-threatening viral infections. One retrospective series examined 26 patients with a PID requiring HCT who had at least one documented serious viral infection and were treated with VST either before or after HCT [19]. Complete or partial antiviral response was seen in 76 to 100 percent of patients, depending upon the particular virus. An additional 10 patients were treated preventively with VST prior to HCT. Of these, eight remained free of the most common serious viral infections. This therapy is still experimental, but commercial entities are developing these cellular products and they may be available for more widespread use in a few years. (See "Severe combined immunodeficiency (SCID): An overview", section on 'Treatment'.)

Dosing of direct oral anticoagulants in obese patients (June 2016) Limited data are available to guide dosing of direct oral anticoagulants (DOACs; dabigatran, apixaban, edoxaban, rivaroxaban) in patients with obesity. The International Society of Thrombosis and Hemostasis (ISTH) has issued guidance on this subject [25]. The major recommendations include use of DOACs at standard doses for those with a body mass index (BMI) â&#x2030;¤40 kg/m2 or weight <120 kg, and avoidance of DOACs in individuals with a BMI >40 kg/m2 or weight â&#x2030;Ľ120 kg. (See "Direct oral anticoagulants: Dosing and adverse effects".)

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Vascular disease in patients with CML taking tyrosine kinase inhibitors (June 2016) For the initial treatment of chronic myeloid leukemia (CML), the second-generation tyrosine kinase inhibitors (TKIs) nilotinib and dasatinib are able to achieve faster and deeper responses than imatinib, but have a different toxicity profile, including increased cardiovascular toxicity. A retrospective cohort study used a Swedish population-based registry to analyze the risk of vascular events in 896 patients with chronic-phase CML treated with imatinib, dasatinib, or nilotinib [9].

When compared with age- and sex-matched controls, patients treated with any TKI had an increased risk of vascular events, but the association was greater with the second-generation agents. Event rates for myocardial infarction among patients treated with nilotinib, dasatinib and imatinib were 29, 19, and 8 per 1000 person-years, respectively. These findings underscore the importance of screening for and optimal management of traditional cardiac risk factors. Although it is not known whether anticoagulation helps, many clinicians offer low-dose aspirin for general cardiovascular prophylaxis in patients taking TKIs. (See "Clinical use of tyrosine kinase inhibitors for chronic myeloid leukemia", section on 'Vascular disease'.)

Maintenance rituximab after bendamustine plus rituximab in mantle cell lymphoma (June 2016) Maintenance rituximab improves progression-free survival (PFS) and may improve overall survival in patients with mantle cell lymphoma (MCL) treated with R-CHOP induction, but its role after induction with bendamustine plus rituximab (BR) is not well understood. In a preliminary report, presented in abstract form, a randomized phase 2 trial comparing two years of maintenance rituximab versus observation in 168 patients with newly diagnosed MCL treated with BR induction showed no significant difference in PFS at a median follow-up of 59 months (HR 0.71; 95% CI 0.411.23; median 55 versus 72 months) [37]. For patients with newly diagnosed MCL who have had at least a partial response to initial therapy and are not eligible for autologous hematopoietic cell transplantation (HCT), the decision to use maintenance rituximab must take into account the initial therapy administered. Given the lack of a PFS benefit in this randomized trial, we suggest observation rather than maintenance following BR induction. In contrast, for those receiving R-CHOP induction, we suggest the use of maintenance rituximab until progression, rather than observation with treatment at the time of progression. (See "Initial treatment of mantle cell lymphoma", section on 'Maintenance therapy'.)

R-CHOP/R-DHAP for mantle cell lymphoma (June 2016) Nonrandomized prospective trials have suggested high rates of deep responses in patients with mantle cell lymphoma (MCL) treated with alternating cycles of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) and R-DHAP (rituximab, dexamethasone, high-dose cytarabine, and cisplatin) followed by autologous hematopoietic cell transplantation (HCT). A randomized trial in 497 younger adults with previously untreated MCL compared six cycles of this regimen versus six cycles of R-CHOP, both followed by autologous HCT [38]. After a median follow-up of six years, R-CHOP/R-DHAP resulted in longer time to treatment failure (median nine versus four years), but this has yet to translate into a statistically significant survival benefit (HR 0.78; 95% CI 0.57-1.07). R-CHOP/R-DHAP was associated with higher rates of hematologic toxicity, febrile neutropenia, and renal toxicity. We do not routinely use R-CHOP/RDHAP due to toxicity concerns and lack of a proven survival benefit. (See "Initial treatment of mantle cell lymphoma", section on 'Conventional chemoimmunotherapy'.)

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NICE guidance/evidence:

QS12 Breast cancer Quality standard This quality standard covers the management of early (ductal carcinoma in situ and invasive), locally advanced and advanced breast cancer, recurrent breast cancer and familial breast cancer in adults.

This includes breast cancer identified through screening and by assessment of symptoms, and covers care from the point of referral to a specialist team. It does not cover adults with non-cancerous breast tumours.

Thousands of men with enlarged prostates could be helped by new NICE guidance on laser device NICE The guidance recommends the GreenLight XPS laser system for patients who arenâ&#x20AC;&#x2122;t at high risk of complications from treatment, such as those men without urinary retention or an increased risk of bleeding, and whose prostates are smaller than 100ml. The NICE committee found that men benefit from a quicker return to normal activity following treatment and a shorter period of time in hospital because the Greenlight XPS procedure can be done as a day-case. The NHS also benefits: NICE estimates up to an estimated ÂŁ3 million could be saved by using this device when compared with the commonly used procedure transurethral resection of the prostate (TURP) because TURP requires an overnight stay in hospital.

BMJ Evidence Updates (you may need to logon to BMJ): Efficacy of the MAGE-A3 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small-cell lung cancer (MAGRIT): a randomised, double-blind, placebocontrolled, phase 3 trial.

Lancet Oncol Timing of androgen-deprivation therapy in patients with prostate cancer with a rising PSA (TROG 03.06 and VCOG PR 01-03 [TOAD]): a randomised, multicentre, non-blinded, phase 3 trial.

Lancet Oncol Breast Cancer Therapy-Related Cardiac Dysfunction in Adult Women Treated in Routine Clinical Practice: A Population-Based Cohort Study.

J Clin Oncol 15

Narrow band imaging optical diagnosis of small colorectal polyps in routine clinical practice: the Detect Inspect Characterise Resect and Discard 2 (DISCARD 2) study.

Gut Development and external validation of two nomograms to predict overall survival and occurrence of distant metastases in adults after surgical resection of localised soft-tissue sarcomas of the extremities: a retrospective analysis.

Lancet Oncol Pre-surgical Administration of Microbial Cell Preparation in Colorectal Cancer Patients: A Randomized Controlled Trial.

World J Surg Association Between Helicobacter pylori Eradication and Gastric Cancer Incidence: A Systematic Review and Meta-analysis.

Gastroenterology First-line treatment of advanced epidermal growth factor receptor (EGFR) mutation positive nonsquamous non-small cell lung cancer.

Cochrane Database Syst Rev Eight Cycles of ABVD Versus Four Cycles of BEACOPPescalated Plus Four Cycles of BEACOPPbaseline in Stage III to IV, International Prognostic Score >/= 3, High-Risk Hodgkin Lymphoma: First Results of the Phase III EORTC 20012 Intergroup Trial.

J Clin Oncol Response to Cetuximab With/ Without Irinotecan in Patients With Refractory Metastatic Colorectal Cancer Harboring the KRAS G13D Mutation: Australasian Gastro-Intestinal Trials Group .

J Clin Oncol A Randomized Phase II Trial of Short-Course Androgen Deprivation Therapy With or Without Bevacizumab for Patients With Recurrent Prostate Cancer After Definitive Local Therapy.

J Clin Oncol Follow-up strategies for women treated for early breast cancer.

Cochrane Database Syst Rev Controlled, Randomized, Open-Label Trial of Risk-Stratified Corticosteroid Prevention of Acute GraftVersus-Host Disease After Haploidentical Transplantation.

J Clin Oncol High-dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with early poor prognosis breast cancer.

Cochrane Database Syst Rev Intravesical Bacillus Calmette-Guerin Versus Combination of Epirubicin and Interferon-alpha2a in Reducing Recurrence of Non-Muscle-invasive Bladder Carcinoma: FinnBladder-6 Study.

Eur Urol Cancer risk in patients with spondyloarthritis treated with TNF inhibitors: a collaborative study from the ARTIS and DANBIO registers.

Ann Rheum Dis First-line chemotherapy in low-risk gestational trophoblastic neoplasia.

Cochrane Database Syst Rev 16

Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years.

N Engl J Med Phase III Trial Evaluating Letrozole As First-Line Endocrine Therapy With or Without Bevacizumab for the Treatment of Postmenopausal Women With Hormone Receptor-Positive Advanced-Stage Breast Cancer: CALGB 40503 (Alliance).

J Clin Oncol Adjuvant chemotherapy of S-1 versus gemcitabine for resected pancreatic cancer: a phase 3, openlabel, randomised, non-inferiority trial (JASPAC 01).

Lancet Olaratumab and doxorubicin versus doxorubicin alone for treatment of soft-tissue sarcoma: an open-label phase 1b and randomised phase 2 trial.

Lancet Two Years of Adjuvant Tamoxifen Provides a Survival Benefit Compared With No Systemic Treatment in Premenopausal Patients With Primary Breast Cancer: Long-Term Follow-Up (> 25 years) of the Phase III SBII:2pre Trial.

J Clin Oncol Salvage radiotherapy with or without short-term hormone therapy for rising prostate-specific antigen concentration after radical prostatectomy (GETUG-AFU 16): a randomised, multicentre, open-label phase 3 trial.

Lancet Oncol Screening for Colorectal Cancer: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force.

JAMA Inotuzumab Ozogamicin versus Standard Therapy for Acute Lymphoblastic Leukemia.

N Engl J Med Complete lymph node dissection versus no dissection in patients with sentinel lymph node biopsy positive melanoma (DeCOG-SLT): a multicentre, randomised, phase 3 trial.

Lancet Oncol Pictilisib for oestrogen receptor-positive, aromatase inhibitor-resistant, advanced or metastatic breast cancer (FERGI): a randomised, double-blind, placebo-controlled, phase 2 trial.

Lancet Oncol From Public Health England: Health matters: improving the prevention and diagnosis of bowel cancer Published 27 June 2016 https://www.gov.uk/government/publications/health-matters-preventing-bowel-cancer/healthmatters-improving-the-prevention-and-detection-of-bowel-cancer

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CANCER IN THE NEWS BACK TO TOP

Pioneering cancer drug combination approved “A pioneering pair of cancer drugs that unleash the immune system on tumours will be paid for by the NHS in England. In trials, the combination therapy shrank the most aggressive and deadly type of skin cancer in 69% of patients. The decision to approve the drugs is one of the fastest in NHS history and is likely to be adopted throughout the UK…” Article based on this from NICE: Melanoma (advanced, unresectable, metastatic) - nivolumab (with ipilimumab) [ID848]

An article in the Guardian: Quote: “Scientists uncover 11 types of acute myeloid leukaemia… The blood cancer known as acute myeloid leukaemia (AML) is not one disease but at least 11 different types, scientists have concluded by studying the genes that cause the condition. Scientists say the discovery could aid diagnosis and lead to new treatments geared towards tackling the different types of the disease….Published in the New England Journal of Medicine the study, hailed as the largest of its kind, involved the analysis of 111 leukaemia-related genes in 1,540 AML patients taking part in clinical trials. The scientists then unpicked patterns between mutations in these genes and the way in which the leukaemia progressed….While many patients had a unique collection of mutations with their genes, the research revealed that there were 11 broad classes of AML, eight of which had previously been proposed. “Within each of those 11 classes there are some key genetic events, which you see only in that subtype of leukaemia and not in other subtypes,” said Campbell [co-author].”

Here is the paper referred to: Genomic Classification and Prognosis in Acute Myeloid Leukemia N Engl J Med 2016; 374:2209-2221June 9

Research raises hope of a 'Holy Grail' universal cancer vaccine "'Universal cancer vaccine' breakthrough claimed by experts," The Independent reports. Researchers extracted genetic code called RNA from cancer cells, embedded them in nanoparticles to make them appear like viruses or bacteria, and injected them into mice to "teach" immune cells to attack cancer cells…

Article based on this paper: Kranz LM, Diken M, Haas H, et al. Systemic RNA delivery to dendritic cells exploits antiviral defence for cancer immunotherapy. Nature. Published online June 1 2016

Bowel cancer: Stents 'may prevent need for colostomy bags', BBC News A expandable tube, or stent, inserted into the bowels of cancer patients can cut the odds of them needing a colostomy bag, cancer doctors say. Read the full story

Could statins prevent breast cancer returning?

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"Statins could be used in the treatment of breast cancer," Sky News report. Findings from a new study suggest the potential involvement of cholesterol in the recurrence of breast cancer following treatment. The researchers hope their discovery could pave the way towards new treatment targets, and say that the effect of cholesterol-lowering drugs (such as statins) now needs to be examined…

Article based on this paper: Simigdala N, Gao Q, Pancholi S, Roberg-Larsen H, et al. Cholesterol biosynthesis pathway as a novel mechanism of resistance to estrogen deprivation in estrogen receptor-positive breast cancer. Breast Cancer Research. Published online June 1 2016

Treatment 'breakthrough' in man with advanced skin cancer "Skin cancer cure hope for millions as major treatment breakthrough sees man's tumours disappear 'completely'," the Daily Mirror reports. While the headline is premature, the case report it is based on does present interesting findings. The study involved a man with melanoma – the most serious type of skin cancer – that had spread to other parts of the body. He was entered into a small trial to try a combination of immunotherapy treatments, which involves stimulating the immune system to detect and kill cancer cells Article based on following paper: Chapuis AG, Lee SM, Thompson JA, et al. Combined IL-21–primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient. Journal of Experimental Medicine. Published online May 30 2016

New radiotherapy regime for prostate cancer could save NHS tens of millions per year A shorter course of prostate cancer radiotherapy, involving fewer hospital visits and higher individual doses of radiotherapy, is as effective as the current standard treatment for both survival and quality of life, a major new study reports. Researchers leading the 14-year trial — published in The Lancet Oncology today — believe the new treatment schedule would be more convenient for patients and could save the NHS tens of millions of pounds per year. The study, led by a team at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, found benefits for a 20-dose course of a modern type of radiotherapy over a 37-dose course, which is the current NHS standard. The researchers said the findings of their study, which was funded by Cancer Research UK, supported a change in clinical practice for prostate cancer radiotherapy with the 20dose schedule becoming the new standard.

Landmark study gives clearest picture of genetic causes of bowel cancer A landmark study has given the most detailed picture yet of the genetics of bowel cancer — the UK's fourth most common cancer. The study examined all the genes from more than 1,000 people with bowel cancer and is the largest of its type ever conducted. A team led by scientists at The Institute of Cancer Research, London, uncovered five new potential genes which, when mutated, appeared to cause bowel cancer in a very low proportion of cases. Further research is needed to confirm these links as the mutations were very rare — each being linked to only a handful of cases in the 1,000strong patient cohort.

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The study, largely funded by Cancer Research UK, also concluded that the major genes that greatly increase the risk of bowel cancer have now almost certainly been found. The research was published in Nature Communications on Wednesday 22 June 2016.

In brief: Research raises hope of a 'Holy Grail' universal cancer vaccine Could statins prevent breast cancer returning?

Novel Antibody Helps Patients With Advanced Gastric Cancer Live Longer Adding Intraperitoneal Chemotherapy Slows Ovarian Cancer Progression New Antibody Drug Conjugate Shows Early Promise in Small Cell Lung Cancer Patients With Advanced Bladder Cancer Benefit From Anti-PD-L1 Immunotherapy Chemotherapy Combination With Capecitabine Extends Survival After Pancreatic Cancer Surgery Ten Years of Hormone Therapy Reduces Breast Cancer Recurrence Without Compromising Quality of Life Breast cancer: Taking hormonal drugs for up to 15 years can reduce risk - study Genetic chaos in tumours could predict responses to immunotherapy Doubling-up on cancer immunotherapy shows promise, but side effects still a challenge Defining cancers based on genetic â&#x20AC;&#x2DC;fingerprintâ&#x20AC;&#x2122; could help personalise treatment

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REPORTS, PUBLICATIONS AND RESOURCES

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From NICE: Melanoma (advanced, unresectable, metastatic) - nivolumab (with ipilimumab) [ID848] Following the CHMP positive opinion, the company met with the NICE team and proposed that the three scopes for nivolumab monotherapy (ID845, ID846 and ID847) could be combined into one Single Technology Appraisal (STA), with a second STA for nivolumab in combination with ipilimumab (ID848) to follow in line with the proposed license extension.

ESTRO Newslatter http://www.estro.org/binaries/content/assets/estro/about/newsletter/2016/160629-newsletter-julyaugust-final.pdf

American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline.

The purpose of the American Cancer Society/American Society of Clinical Oncology Breast Cancer Survivorship Care Guideline is to provide recommendations to assist primary care and other clinicians in the care of female adult survivors of breast cancer. A systematic review of the literature was conducted using PubMed through April 2015. A multidisciplinary expert workgroup with expertise in primary care, gynecology, surgical oncology, medical oncology, radiation oncology, and nursing was formed and tasked with drafting the Breast Cancer Survivorship Care Guideline. A total of 1,073 articles met inclusion criteria; and, after full text review, 237 were included as the evidence base.

Patients should undergo regular surveillance for breast cancer recurrence, including evaluation with a cancer-related history and physical examination, and should be screened for new primary breast cancer. Data do not support performing routine laboratory tests or imaging tests in asymptomatic patients to evaluate for breast cancer recurrence. Primary care clinicians should counsel patients about the importance of maintaining a healthy lifestyle, monitor for post-treatment symptoms that can adversely affect quality of life, and monitor for adherence to endocrine therapy. Recommendations provided in this guideline are based on current evidence in the literature and expert consensus opinion. Most of the evidence is not sufficient to warrant a strong evidence-based recommendation.

Recommendations on surveillance for breast cancer recurrence, screening for second primary cancers, assessment and management of physical and psychosocial long-term and late effects of breast cancer and its treatment, health promotion, and care coordination/practice implications are made. This guideline was developed through a collaboration between the American Cancer Society and the American Society of Clinical Oncology and has been published jointly by invitation and consent in both CA: A Cancer Journal for Clinicians and Journal of Clinical Oncology. All rights reserved. No part of this document may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopy, recording, or any information storage and retrieval system, without written permission by the American Cancer Society or the American Society of Clinical Oncology.

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TRAINING & NETWORKING OPPORTUNITIES, CONFERENCES, EVENTS BACK TO TOP

6th ICHNO International conference on innovative approaches in head & neck oncology Joint ESTRO, ESMO, EHNS 16-18 March 2017; Barcelona, Spain Deadlines: Abstract submission: 12 October 2016; Early registration: 26 October 2016

ECCO 2017 European Cancer Congress 27-30 January 2017, Amsterdam, The Netherlands Download the advance programme Deadlines: Abstract submission: 25 August 2016; Early registration: 27 June 2016

GEC-ESTRO workshop 2-3 November 2016 Poznan, Poland “Techniques, Trials and Technologies for Brachy-therapy Patients”

Free Event: Future horizons in lung cancer – London 2016

01 SEP This free event the Royal Society of Medicine on 1 and 2 September is designed to meet the educational needs of practitioners on the front line - the Future Horizons in Lung Cancer meeting is a chance to gain valuable insights and interact directly with a faculty of experts from the USA and Europe.

Cutting edge science, the identification of more targets, and the advent of ground-breaking new classes of drugs demands that healthcare professionals are constantly updated and actively revise treatment algorithms to offer the best possible outcomes for our patients.

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The Future Horizons in Lung Cancer meeting will address this need, focusing on the dissemination of exciting new developments from across the field.

By the end of this meeting delegates will be able to understand NSCLC and SCLC including the current standards of care and the impact of new therapies, know what is new in radiotherapy, imaging and pet tracers, and understand the latest in omics and early detection, and how immunotherapy will impact standards of care.

For more information please click HERE

ASP Supportive and Palliative Care Conference 2016

16 SEP The Association for Palliative Medicine of Great Britain and Ireland is hosting the APM Supportive and Palliative Care Conference (ASP Conference) 30 and 31 March 2017 at Belfast Waterfront Northern Ireland. The call for papers is now open and submission guidelines are available.

The abstract deadline is 16 September 2016.

For further information please click HERE

Odyssey Fourth Cancer Survivorship Conference 2016 2016

30 SEP Odyssey Challenging Cancer is a unique organisation which enhances the quality of life for people with cancer. Odysseyâ&#x20AC;&#x2122;s Fourth Cancer Survivorship Conference will be held at Queens College, Oxford on Friday 30 September 2016.

To find out more please click HERE

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OTHER SERVICES, 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.

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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

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.

NEW! Library training drop-in sessions The Library at Musgrove Park Academy is running a series of drop-in sessions that will be held in the Academy e-learning room. No booking necessary, but if you decide to attend you will need to arrive on time.    

Introduction to Critical Appraisal Evidence Searching Literature Searching Rapid Evidence review

For a list of the course dates click here

NEW! Horizon Scanning service Horizon Scanning – also known as Early Warning Systems - is a systematic examination of information to identify potential threats, risks, emerging issues and opportunities and filter and

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prioritise new and emerging health technologies. Horizon Scanning service maps ‘forward alerts’ and ‘evidence predictions’, based on emerging trends. Sources searched include the usual clinical evidence sources, as well as ‘grey literature’, specialist medicines databases, health technology databases and specialist Horizon Scanning databases.

To access, click here.

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