Clinical Librarian Service Musgrove Park Academy
Current Awareness
Cancer Issue 6 June 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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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
Identification of an activation site in Bak and mitochondrial Bax triggered by antibodies Nature Communications 7,Article number: 24 May 2016 Sweta Iyer, Khatira Anwari, Amber E. Alsop, et al During apoptosis, Bak and Bax are activated by BH3-only proteins binding to the α2–α5 hydrophobic groove; Bax is also activated via a rear pocket. Here we report that antibodies can directly activate Bak and mitochondrial Bax by binding to the α1–α2 loop. A monoclonal antibody (clone 7D10) binds close to α1 in non-activated Bak to induce conformational change, oligomerization, and cytochrome c release. Anti-FLAG antibodies also activate Bak containing a FLAG epitope close to α1. An antibody (clone 3C10) to the Bax α1–α2 loop activates mitochondrial Bax, but blocks translocation of cytosolic Bax. Tethers within Bak show that 7D10 binding directly extricates α1; a structural model of the 7D10 Fab bound to Bak reveals the formation of a cavity under α1. Our identification of the α1–α2 loop as an activation site in Bak paves the way to develop intrabodies or small molecules that directly and selectively regulate these proteins.
Combined IL-21–primed polyclonal CTL plus CTLA4 blockade controls refractory metastatic melanoma in a patient Journal of Experimental Medicine, Published 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
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Dormant breast cancer micrometastases reside in specific bone marrow niches that regulate their transit to and from bone Science Translational Medicine 25 May 2016: Vol. 8, Issue 340, pp. 340ra73 Breast cancer metastatic relapse can occur years after therapy, indicating that disseminated breast cancer cells (BCCs) have a prolonged dormant phase before becoming proliferative. A major site of disease dissemination and relapse is bone, although the critical signals that allow circulating BCCs to identify bone microvasculature, enter tissue, and tether to the microenvironment are poorly understood. Using real-time in vivo microscopy of bone marrow (BM) in a breast cancer xenograft model, we show that dormant and proliferating BCCs occupy distinct areas, with dormant BCCs predominantly found in E-selectin– and stromal cell–derived factor 1 (SDF-1)–rich perisinusoidal vascular regions. We use highly specific inhibitors of E-selectin and C-X-C chemokine receptor type 4 (CXCR4) (SDF-1 receptor) to demonstrate that E-selectin and SDF-1 orchestrate opposing roles in BCC trafficking. Whereas E-selectin interactions are critical for allowing BCC entry into the BM, the SDF1/CXCR4 interaction anchors BCCs to the microenvironment, and its inhibition induces mobilization of dormant micrometastases into circulation. Homing studies with primary BCCs also demonstrate that E-selectin regulates their entry into bone through the sinusoidal niche, and immunohistochemical staining of patient BMs shows dormant micrometastatic disease adjacent to SDF-1+ vasculature. These findings shed light on how BCCs traffic within the host, and suggest that simultaneous blockade of CXCR4 and E-selectin in patients could molecularly excise dormant micrometastases from the protective BM environment, preventing their emergence as relapsed disease.
Landscape of somatic mutations in 560 breast cancer whole-genome sequences Nature, 02 May 2016 We analysed whole-genome sequences of 560 breast cancers to advance understanding of the driver mutations conferring clonal advantage and the mutational processes generating somatic mutations. We found that 93 protein-coding cancer genes carried probable driver mutations. Some non-coding regions exhibited high mutation frequencies, but most have distinctive structural features probably causing elevated mutation rates and do not contain driver mutations. Mutational signature analysis was extended to genome rearrangements and revealed twelve base substitution and six rearrangement signatures. Three rearrangement signatures, characterized by tandem duplications or deletions, appear associated with defective homologous-recombination-based DNA repair: one with deficient BRCA1 function, another with deficient BRCA1 or BRCA2 function, the cause of the third is unknown. This analysis of all classes of somatic mutation across exons, introns and intergenic regions highlights the repertoire of cancer genes and mutational processes operating, and progresses towards a comprehensive account of the somatic genetic basis of breast cancer
Benefit of Surveillance for Pancreatic Cancer in High-Risk Individuals: Outcome of Long-Term Prospective Follow-Up Studies From Three European Expert Centers 4
Hans Vasen, Isaura Ibrahim, Carmen Guillen Ponce, Emily P. Slater, et al JCO April 25, 2016 JCO640730 Four hundred eleven asymptomatic individuals participated in the surveillance programs, including 178 CDKN2A mutation carriers, 214 individuals with FPC, and 19 BRCA1/2 or PALB2 mutation carriers. PDAC was detected in 13 (7.3%) of 178 CDKN2A mutation carriers. The resection rate was 75%, and the 5-year survival rate was 24%. Two CDKN2A mutation carriers (1%) underwent surgical resection for low-risk PRL. Two individuals (0.9%) in the FPC cohort had a pancreatic tumor, including one advanced PDAC and one early grade 2 neuroendocrine tumor. Thirteen individuals with FPC (6.1%) underwent surgical resection for a suspected PRL, but only four (1.9%) had high-risk lesions (ie, high-grade intraductal papillary mucinous neoplasms or grade 3 pancreatic intraepithelial neoplasms). One BRCA2 mutation carrier was found to have PDAC, and another BRCA2 mutation carrier and a PALB2 mutation carrier underwent surgery and were found to have low-risk PRL. No serious complications occurred as consequence of the program. Conclusion: Surveillance of CDNK2A mutation carriers is relatively successful, detecting most PDACs at a resectable stage. The benefit of surveillance in families with FPC is less evident.
Practice development using video-reflexive ethnography: promoting safe space(s) towards the end of life in hospital Aileen Collier International Practice Development Journal 6 (1) [3] The theories underpinning video-reflexive ethnography and practice development are closely aligned; the former has potential as a practice development methodology to promote personcentred palliative and end-of-life care. The underpinning philosophical, ethical and values framework through which it is applied, along with the skills and aptitude of facilitation, are critical if its potential is to be realised. The delivery of person-centred end-of-life care may be facilitated by: • Healthcare workers seeing themselves and those they care for differently • Healthcare organisations seeing their employees as well as patients and families differently • Researchers also being prepared to see themselves differently • The use of video-reflexive ethnography as a potential practice development methodology tomeet these objectives
Assessment of the Predictive Value of the Modified Frailty Index for Clavien-Dindo Grade IV Critical Care Complications in Major Head and Neck Cancer Operations 5
JAMA Otolaryngol Head Neck Surg. Original Investigation|May 12, 2016 The mFI is predictive of postoperative critical care support after surgery for head and neck cancer. Specifically, increases in mFIs were strongly associated with CDIV complications for glossectomy, mandibulectomy, and laryngectomy. Classifying patients by their functional status using the mFI may help predict outcomes after head and neck oncologic surgery.
Radiotherapy versus Prostatectomy: a Question of Survival or Survivorship? Addressing Ongoing Questions and Controversies in the Management of Localised Prostate Cancer in the UK DOI http://dx.doi.org/10.1016/j.clon.2016.04.050 SA. Mangar The landscape of prostate cancer is evolving. Although the introduction of prostate-specific antigen (PSA) testing into clinical practice some 30 years ago has seen a greater detection of organ-confined disease due to stage migration, as yet this has not resulted in any significant reduction in mortality. In addition, although a third of cases are diagnosed in men above the age of 75 years, only a minority actually undergo curative treatment, leaving a significant proportion of men having to live with their prostate cancer.
Analysis of Clinical End Points of Randomised Trials Including Bevacizumab and Chemotherapy versus Chemotherapy as First-line Treatment of Metastatic Colorectal Cancer DOI: http://dx.doi.org/10.1016/j.clon.2016.05.001 Progression-free survival is closely related to overall survival (r=0.817; R2=0.706) and this relationship does not seem to be changed by the discontinuation of bevacizumab. The responserelated end points have a better overall performance than the other time-to-event end points, even when only phase III trials are considered. In phase III trials, the disease control rate seems to be strongly related to overall survival (r=0.975; R2=0.889) and the overall response rate reports a good performance (r=0.866; R2=0.484). An open-label design and the timing of disease radiological evaluation do not seem to interfere with the correlation of differences of progression-free survival and overall survival. A validation of the disease control rate and the overall response rate as a surrogate end point of survival at a patient level and a standardised definition of the timing for their measurement are strongly recommended in trials of chemotherapy plus bevacizumab.
Colorectal Cancer on the Decline — Why Screening Can’t Explain It All H. Gilbert Welch, M.D., M.P.H., and Douglas J. Robertson, M.D., M.P.H. N Engl J Med 2016; 374:1605-1607April 28, 2016DOI: 10.1056/NEJMp1600448 6
Unlike screening for breast or prostate cancer, screening for colorectal cancer promises not only to find cancer early, but also to prevent it from occurring. In the 1960s, Gilbertsen first suggested that polypectomy could turn colorectal cancer into a preventable disease.1 Two decades later, Vogelstein envisioned the polyp-to-cancer progression as a stepwise process and detailed the genetic alterations that occur at each step.2 Colorectal cancer became widely viewed as having a long latency period — providing ample time for both early detection and prevention. Conditions were thus considered ideal for screening to reduce related mortality.
Antiemetic Prophylaxis for Chemotherapy-Induced Nausea and Vomiting Rudolph M. Navari, M.D., Ph.D., and Matti Aapro, M.D. N Engl J Med 2016; 374:1356-1367April 7, 2016 One of the most important changes in cancer treatment in recent decades has been the development of treatment regimens that greatly reduce the incidence and intensity of nausea and vomiting. The most effective regimens and how they work are reviewed.
Breast Cancer Therapy–Related Cardiac Dysfunction in Adult Women Treated in Routine Clinical Practice: A Population-Based Cohort Study Paaladinesh Thavendiranathan⇑, Husam Abdel-Qadir, Hadas D. Fischer, Ximena Camacho, Eitan Amir, Peter C. Austin and Douglas S. Lee JCO April 18, 2016 JCO651505 Of 18,540 women included (median age, 54 years; interquartile range, 47 to 63 years), 79% were younger than age 65 years. The cumulative incidence of the primary outcome was 3.08% (95% CI, 2.81% to 3.36%) by 3 years of follow-up, whereas in an age-matched sample of Ontario women (n = 92,700) without breast cancer, it was 0.96% (95% CI, 0.89% to 1.04%). Compared with those receiving other chemotherapy, patients receiving trastuzumab with nonanthracycline chemotherapy and sequential therapy were at a higher risk of cardiotoxicity (hazard ratio, 1.76 [95% CI, 1.19 to 2.60] and 3.96 [95% CI, 3.01 to 5.22], respectively). Hospital-based CHF events were only increased with sequential therapy (hazard ratio, 1.86; 95% CI, 1.07 to 3.22). Conclusion In women with breast cancer and an age distribution representative of routine clinical practice, trastuzumab-based regimens, including those without anthracyclines, were associated with an increased risk of cardiotoxicity. Sequential therapy increased the risk of hospital-based CHF events
Clinical Implications of Genomic Discoveries in Lung Cancer Charles Swanton and Ramaswamy Govindan N Engl J Med 2016; 374:1864-1873May 12, 2016 7
Many genetic lesions have been identified in lung cancers. The findings shed light on molecular pathogenesis and have led to the definition of abnormalities that can be targeted by therapeutic agents that occasionally elicit dramatic responses.
Evaluating Cancer of the Central Nervous System Through Next-Generation Sequencing of Cerebrospinal Fluid Elena I. Pentsova, Ronak H. Shah, Jiabin Tang et al JCO May 9, 2016 We detected high-confidence somatic alterations in 63% (20 of 32) of patients with CNS metastases of solid tumors, 50% (six of 12) of patients with primary brain tumors, and 0% (zero of nine) of patients without CNS involvement by cancer. Several patients with tumor progression in the CNS during therapy with inhibitors of oncogenic kinases harbored mutations in the kinase target or kinase bypass pathways. In patients with glioma, the most common malignant primary brain tumor in adults, examination of cell-free DNA uncovered patterns of tumor evolution, including temozolomide-associated mutations. The study shows that CSF harbors clinically relevant genomic alterations in patients with CNS cancers and should be considered for liquid biopsies to monitor tumor evolution in the CNS.
Venetoclax in relapsed or refractory chronic lymphocytic leukaemia with 17p deletion: a multicentre, open-label, phase 2 study Stephan Stilgenbauer et al Results of this trial show that venetoclax monotherapy is active and well tolerated in patients with relapsed or refractory del(17p) chronic lymphocytic leukaemia, providing a new therapeutic option for this very poor prognosis population. Additionally, in view of the distinct mechanism-of-action of venetoclax, combinations or sequencing with other novel targeted agents should be investigated to further advance treatment of del(17p) chronic lymphocytic leukaemia.
An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a metaanalysis of individual patient data The International CLL-IPI working group The CLL-IPI combines genetic, biochemical, and clinical parameters into a prognostic model, discriminating four prognostic subgroups. The CLL-IPI will allow a more targeted management of patients with chronic lymphocytic leukaemia in clinical practice and in trials testing novel drugs.
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5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial Lucca Giani et al Progression-free survival and disease-free survival at 5-year follow-up show large and overlapping CIs, but support the primary endpoint (pathological complete response) and suggest that neoadjuvant pertuzumab is beneficial when combined with trastuzumab and docetaxel. Additionally, they suggest that total pathological complete response could be an early indicator of long-term outcome in early-stage HER2-positive breast cancer.
Association Between Complementary and Alternative Medicine Use and Breast Cancer Chemotherapy Initiation: The Breast Cancer Quality of Care (BQUAL) Study JAMA Oncol. Published online May 12, 2016. A cohort of 685 women younger than 70 years (mean age, 59 years; median age, 59 years) with nonmetastatic invasive breast cancer were recruited and followed for up to 12 months to examine predictors of breast cancer treatment initiation. Baseline CAM use was reported by 598 women (87%). Chemotherapy was initiated by 272 women (89%) for whom chemotherapy was indicated, compared with 135 women (36%) for whom chemotherapy was discretionary. Among women for whom chemotherapy was indicated, dietary supplement users and women with high CAM index scores were less likely than nonusers to initiate chemotherapy (odds ratio [OR], 0.16; 95% CI, 0.030.51; and OR per unit, 0.64; 95% CI, 0.46-0.87, respectively). Use of mind-body practices was not related to chemotherapy initiation (OR, 1.45; 95% CI, 0.57-3.59). There was no association between CAM use and chemotherapy initiation among women for whom chemotherapy was discretionary. 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.
A phase II study of a modified FOLFOX6 regimen as neoadjuvant chemotherapy for locally advanced gastric cancer Xiang Wang et al British Journal of Cancer , 12 May 2016 Sixty-seven (91.8%) patients completed 3 cycles, with grade 3–4 toxicity arising in 33.0%. The radiology response rate was 45.8%. Sixty-seven (91.8%) patients receiving radical surgery showed different levels of histological regression of the primary tumour, with a 50% regression rate of 49.2%. ypTNM stage (HR 4.045, 95% CI 1.429–11.446) and tumours of diffuse and mixed type (HR 9
9.963, 95% CI 1.937–51.235; HR 8.890, 95% CI 1.157–68.323, respectively) were significantly associated with OS. The pathologic regression rate (GHR; 2/3/<2/3, 50%/<50%) was statistically significantly associated with OS according to a univariate analysis. Perioperative mFOLFOX6 was a tolerable and effective regimen for gastric cancer. The ypTNM stage was an independent predictor of survival. GHR 50%/<50% could be used as a surrogate marker for selecting a postoperative chemotherapy regimen.
Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as firstline treatment for patients with metastatic colorectal cancer (WJOG4407G) K Yamazaki et al Ann Oncol May 13, 2016 Among 402 patients enrolled from September 2008 to January 2012, 395 patients were eligible for efficacy analysis. Median PFS for FOLFIRI+Bev (n=197) and mFOLFOX6+Bev (n=198) were 12.1 and 10.7 months, respectively (HR, 0.905; 95% CI, 0.723 to 1.133; P=0.003 for non-inferiority). Median OS for FOLFIRI+Bev and mFOLFOX6+Bev were 31.4 and 30.1 months, respectively (HR, 0.990; 95% CI, 0.785 to 1.249). The best overall response rates were 64% for FOLFIRI+Bev and 62% for mFOLFOX6+Bev. The common grade 3 or higher adverse events were leukopenia (11% in FOLFIRI+Bev/5% in mFOLFOX6+Bev), neutropenia (46%/35%), diarrhea (9%/5%), febrile neutropenia (5%/2%), peripheral neuropathy (0%/22%), and venous thromboembolism (6%/2%). The QoL assessed by FACT-C (TOI-PFC) and FACT/GOG-Ntx was favorable for FOLFIRI+Bev during 18 months. FOLFIRI plus bevacizumab was non-inferior for PFS, compared to mFOLFOX6 plus bevacizumab, as the first-line systemic treatment for mCRC.
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 Maria Ekholm et al JCO May 9, 2016 In patients with estrogen receptor–positive tumors (n = 362), tamoxifen was associated with a marginal reduction in CM (hazard ratio [HR], 0.77; 95% CI, 0.58 to 1.03; P = .075) and a significant reduction in CBCM (HR, 0.73; 95% CI, 0.53 to 0.99; P = .046). The effect seemed to vary over time (CM years 0 to 5: HR, 1.05; 95% CI, 0.64 to 1.73; years > 5 to 15: HR, 0.58; 95% CI, 0.37 to 0.91; and after 15 years: HR, 0.82; 95% CI, 0.48 to 1.42; CBCM years 0 to 5: HR, 1.09; 95% CI, 0.65 to 1.82; years > 5 to 15: HR, 0.53; 95% CI, 0.33 to 0.86; and after 15 years: HR, 0.72; 95% CI, 0.36 to 1.44). Two years of adjuvant tamoxifen resulted in a long-term survival benefit in premenopausal patients with estrogen receptor–positive primary breast cancer.
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Safety and Efficacy of Nivolumab in Patients With Metastatic Renal Cell Carcinoma Treated Beyond ProgressionA Subgroup Analysis of a Randomized Clinical Trial Saby George, MD1; Robert J. Motzer JAMA Oncol. Published online May 12, 2016. Of 168 patients (median [range] age, 61 [37-81] years; 72% male) randomized to nivolumab, 154 experienced progression (36 were treated beyond first progression, 26 were treated beyond first progression for ≤6 weeks, and 92 were not treated beyond first progression), 13 were treated and did not experience progression, and 1 was not treated. Prior to first progression, the RECIST-defined objective response rate was 14% (5 patients) and 16% (15 patients), and median progression-free survival was 4.2 (95% CI, 2.8-5.5) and 2.6 (95% CI, 1.5-3.9) months in patients treated and not treated beyond progression, respectively. Following initial progression, 25 (69%) patients treated beyond progression experienced subsequent tumor reduction or stabilization in target lesion size. The incidence of treatment-related adverse events was higher in patients treated beyond progression (n = 29 [81%]) vs those not treated beyond progression (n = 61 [66%]); however, after adjusting for length of treatment exposure, incidence was lower in patients treated beyond progression (322.9 vs 518.7 incidence rate/100 patient-years for patients treated vs not treated beyond progression). In this subgroup analysis, a proportion of patients who continued treatment beyond RECIST-defined first progression demonstrated sustained reductions in tumor burden or stabilization in the size of target lesions, with an acceptable safety profile. Further analysis will help define the clinical benefit for patients with mRCC treated with nivolumab beyond progression
PIK3CA mutations are associated with reduced pathological complete response rates in primary HER2-positive breast cancer – pooled analysis of 967 patients from five prospective trials investigating lapatinib and trastuzumab S. Loibl et al Ann Oncol : May 13, 2016 Overall PIK3CA mutant/HER2+ tumours had significantly lower pCR rates compared with wild-type, how mainly confined to the HR+/PIK3CA mutant population. No definite conclusions can be drawn regarding survival.
Use and Costs of Disease Monitoring in Women With Metastatic Breast Cancer JCO May 9, 2016 Melissa K Accordino et al We identified 2,460 eligible patients. Of these, 924 (37.6%) were extreme users of diseasemonitoring tests. Factors significantly associated with extreme use were hormone receptor–negative 11
MBC (odds ratio [OR], 1.63; 95% CI, 1.27 to 2.08), history of a positron emission tomography scan (OR, 2.92; 95% CI, 2.40 to 3.55), and more frequent oncology office visits (OR, 3.14; 95% CI, 2.49 to 3.96). Medical costs per year were 59.2% higher in extreme users. Extreme users were more likely to use emergency department and hospice services at the end of life. Despite an unknown clinical benefit, approximately one third of elderly women with MBC were extreme users of diseasemonitoring tests. Higher use of disease-monitoring tests was associated with higher total health care costs. Efforts to understand the optimal frequency of monitoring are needed to inform clinical practice.
Miscellaneous Patientsâ&#x20AC;&#x2122; views of support after cancer treatment Carolina Watters Cancer Nursing Practice 2016 15 (3) p22-28
Role of care co-ordinators in cancer clinical nurse specialist teams Christine Barber Cancer Nursing Practice 2016 15 (3) p31-36
Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: a randomised, open-label, multicentre, phase 3 trial Patrick Schoffski et al Lancet 2016 387 (10028) p1629-1637
Atezolizumab versus docetaxel for patients with previously treated non-small-cell lung cancer (POPLAR): a multicentre, open-label, phase 2 randomised controlled trial Louis Fehrenbacher et al Lancet 2016 387 (10030) p1837-1846
Clinical implications of genomic discoveries in lung cancer C. Swanton et al New England Journal of Medicine 2016 374 (19) p1864-1874
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Cancer management: the difficulties of a target-driven healthcare system Beverley Anderson British Journal of Nursing 2016 25 (9) pS36–S40
Patients’ perceptions of end of treatment consultations for breast cancer Jo Armes Cancer Nursing Practice 2016 15 (4) p28-36
Learning from the experiences of cancer patients and their carers Claire Job et al Cancer Nursing Practice 2016 15 (4) p14-20
Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre phase 2 trial Jonathan E Rosenberg et al Lancet 2016 387 (10031) p1909-1920
A. In brief (you may need to logon to BMJ to see): Breast cancer Staff shortages are putting UK breast cancer screening "at risk," survey finds Anne Gulland Fruit and vegetable consumption in adolescence and early adulthood and risk of breast cancer: population based cohort study Maryam S Farvid, Wendy Y Chen, Karin B Michels, Eunyoung Cho, Walter C Willett, A Heather Eliassen Five year change in alcohol intake and risk of breast cancer and coronary heart disease among postmenopausal women: prospective cohort study Marie K Dam, Ulla A Hvidtfeldt, Anne Tjønneland, Kim Overvad, Morten Grønbæk, Janne S Tolstrup Alcohol, diet, and risk of breast cancer
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Timothy J Key, Gillian K Reeves NICE guidelines on the menopause: NICE guideline committee’s comments on editorial about menopause guideline Grammati Sarri, Melanie Davies, Mary Ann Lumsden Leisure time physical activity is linked to reduced risk of many cancers, review finds Susan Mayor
Colon cancer Barrett’s oesophagus: diagnosis and management Prachi Pophali, Magnus Halland Probiotics have no effect on gut microbiota in healthy people, review suggests Susan Mayor
Lung cancer (oncology) Case Review: Pulmonary nodules in a man with a history of bone marrow transplantation Neil Mendoza, Paritosh Prasad
Prostate cancer Profile: Otis Brawley—one of the first to question the value of screening Jeanne Lenzer Metastatic spinal cord compression: diagnosis and management Rasha Al-Qurainy, Emily Collis
Chemotherapy Older people benefit from intensive blood pressure control Jacqui Wise
Screening (oncology) Case Review: Pulmonary nodules in a man with a history of bone marrow transplantation Neil Mendoza, Paritosh Prasad Staff shortages are putting UK breast cancer screening "at risk," survey finds Anne Gulland Atrial fibrillation in women is linked to increased risk of cancer Jacqui Wise
Cancer: dermatological Spot Diagnosis: A patient with cancer and nail pigmentation Abhishek Maiti, Sreyasi Bhattacharya
Oesophageal cancer Barrett’s oesophagus: diagnosis and management Prachi Pophali, Magnus Halland
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For automated tables of contents: Oncology â&#x20AC;&#x201C; click here Haematology â&#x20AC;&#x201C; click here.
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COCHRANE REVIEWS/UPDATES BACK TO TOP
Chromoscopy versus conventional endoscopy for the detection of polyps in the colon and rectum First published: 7 April 2016 There is strong evidence that chromoscopy enhances the detection of neoplasia in the colon and rectum. People with neoplastic polyps, particularly those with multiple polyps, are at increased risk of developing colorectal cancer. Such lesions, which presumably would be missed with conventional colonoscopy, could contribute to the interval cancer numbers on any surveillance programme.
Interventions for the management of fatigue in adults with a primary brain tumour First published: 13 April 2016 There was insufficient evidence to draw reliable and generalisable conclusions regarding potential effectiveness or harm of any pharmacological or non-pharmacological treatments for fatigue in people with PBT. More research is needed on how best to treat people with brain tumours with high fatigue.
Bortezomib for the treatment of multiple myeloma 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.
Low bacterial diet versus control diet to prevent infection in cancer patients treated with chemotherapy causing episodes of neutropenia
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First published: 24 April 2016 At the moment, no evidence from individual RCTs in children and adults with different malignancies underscores use of an LBD for prevention of infection and related outcomes. All studies differed with regard to co-interventions, outcome definitions and intervention and control diets. As pooling of results was not possible, and as all studies had serious methodological limitations, we could reach no definitive conclusions. It should be noted that 'no evidence of effect', as identified in this review, is not the same as 'evidence of no effect'. On the basis of currently available evidence, we are not able to provide recommendations for clinical practice. Additional high-quality research is needed.
High-dose chemotherapy and autologous bone marrow or stem cell transplantation versus conventional chemotherapy for women with early poor prognosis breast cancer Cochrane Systematic Review 20 May 2016 There is high-quality evidence of increased treatment-related mortality and little or no increase in survival by using high-dose chemotherapy with autograft for women with early poor prognosis breast cancer.
Hyperbaric oxygen therapy for late radiation tissue injury First published: 28 April 2016 These small trials suggest that for people with LRTI affecting tissues of the head, neck, anus and rectum, HBOT is associated with improved outcome. HBOT also appears to reduce the chance of ORN following tooth extraction in an irradiated field. There was no such evidence of any important clinical effect on neurological tissues. The application of HBOT to selected participants and tissues may be justified. Further research is required to establish the optimum participant selection and timing of any therapy. An economic evaluation should be undertaken.
Different types of implants for reconstructive breast surgery First published: 16 May 2016 Despite the central role of breast reconstruction in women with breast cancer, the best implants to use in reconstructive surgery have been studied rarely in the context of RCTs. Furthermore the quality of these studies and the overall evidence they provide is largely unsatisfactory. Some of our results can be interpreted as early evidence of potentially large differences between different surgical approaches, which should be confirmed in new high-quality RCTs that include a larger number of women. These days - even after a few million women have had breasts reconstructed surgeons cannot inform women about the risks and complications of different implant-based breast reconstructive options on the basis of results derived from RCTs.
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OTHER EVIDENCE UPDATES/GUIDANCE BACK TO TOP
Up-to-date latest: click here (you may need to logon via Athens)
NICE guidance/evidence:
TA389
Topotecan, pegylated liposomal doxorubicin hydrochloride, paclitaxel, trabectedin and gemcitabine for treating recurrent ovarian cancer
TA387
Abiraterone for treating metastatic hormone-relapsed prostate cancer before chemotherapy is indicated
TA391
Cabazitaxel for hormone-relapsed metastatic prostate cancer treated with docetaxel
TA384
Nivolumab for treating advanced (unresectable or metastatic) melanoma
NG47
Haematological cancers: improving outcomes
NG35
Myeloma: diagnosis and management
Myeloma treatment is first in new class of gene-influencing anticancer drugs Patients with relapsed or refractory multiple myeloma can now benefit from treatment with the histone deacetylase inhibitor panobinostat (Farydak). Panobinostat causes relaxation of chromatin, which is thought to activate the transcription of tumour suppressor genes. Panobinostat, in combination with bortezomib and dexamethasone, can be used in patients who have already received at least two prior treatments including bortezomib and an immunomodulator. It is taken as capsules once daily on days 1, 3, 5, 8, 10 and 12 of a 21-day cycle, starting at a dose of 20mg. Inhibition of histone deacetylase by panobinostat, leads to increased acetylation of histones, the proteins around which DNA is coiled to form a complex called chromatin. This acetylation results in relaxation of chromatin, which is thought to activate the transcription of tumour suppressor genes involved in cell cycle arrest and apoptosis. 18
Further information: View Farydak drug record Summary of Product Characteristics Manufacturer: Novartis
Survival benefit Approval of panobinostat was based on the results of a randomised, double-blind phase III trial (PANORAMA 1) in patients with relapsed or refractory multiple myeloma who had received one to three previous treatment regimens. Median progression-free survival, the primary endpoint, was significantly longer in patients treated with panobinostat than in those who received placebo, at 11.99 months (95% CI 10.33–12.94) versus 8.08 months (95% CI 7.56–9.23; hazard ratio 0.63, 95% CI 0.52–0.76; p<0.0001).
Diarrhoea and cardiac toxicity Serious adverse events were reported in 60% of patients in the panobinostat group and 42% of patients in the placebo group. Common grade 3–4 laboratory abnormalities and adverse events included thrombocytopenia (67% in the panobinostat group vs 31% in the placebo group), lymphopenia (53% vs 40%), diarrhoea (26% vs 8%), asthenia or fatigue (24% vs 12%), and peripheral neuropathy (18% vs 15%). Blood counts, fluid and electrolyte levels, and liver function must be monitored frequently in patients taking panobinostat and prescribers should be aware of the increased risks of bleeding and infection. Panobinostat may prolong the QT interval and caution is required when it is used in patients with pre-existing QT prolongation or relevant risk factors. Women of childbearing potential should ensure they use contraception during and for 3 months after stopping treatment with panobinostat.
NICE approval NICE recommends panobinostat as an option for treating relapsed and/or refractory multiple myeloma in line with its marketing authorisation. Approval is contingent on the company providing the drug with the discount agreed in the patient access scheme.
BMJ Evidence Updates (you may need to logon to BMJ): Randomized Open-Label Phase II Trial of Apitolisib (GDC-0980), a Novel Inhibitor of the PI3K/Mammalian Target of Rapamycin Pathway, Versus Everolimus in Patients With Metastatic Renal Cell Carcinoma. J Clin Oncol Rituximab and dose-dense chemotherapy for adults with Burkitt`s lymphoma: a randomised, controlled, open-label, phase 3 trial. Lancet 19
A Randomized, Double-Blind, Placebo-Controlled, Phase III Study to Assess Efficacy and Safety of Weekly Farletuzumab in Combination With Carboplatin and Taxane in Patients With Ovarian Cancer in First Platinum-Sensitive Relapse. J Clin Oncol Ganoderma lucidum (Reishi mushroom) for cancer treatment. Cochrane Database Syst Rev Bevacizumab Plus Irinotecan Versus Temozolomide in Newly Diagnosed O6-Methylguanine-DNA Methyltransferase Nonmethylated Glioblastoma: The Randomized GLARIUS Trial. J Clin Oncol Tumour-infiltrating CD8 to FOXP3 lymphocyte ratio in predicting treatment responses to neoadjuvant chemotherapy of aggressive breast cancer. Br J Surg Development and validation of a staging system for HPV-related oropharyngeal cancer by the International Collaboration on Oropharyngeal cancer Network for Staging (ICON-S): a multicentre cohort study. Lancet Oncol Use of Biomarkers to Guide Decisions on Adjuvant Systemic Therapy for Women With Early-Stage Invasive Breast Cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptorpositive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet Systematic review and meta-analysis of the diagnostic accuracy of ductoscopy in patients with pathological nipple discharge. Br J Surg Docetaxel As Monotherapy or Combined With Ramucirumab or Icrucumab in Second-Line Treatment for Locally Advanced or Metastatic Urothelial Carcinoma: An Open-Label, Three-Arm, Randomized Controlled Phase II Trial. J Clin Oncol Acupuncture As an Integrative Approach for the Treatment of Hot Flashes in Women With Breast Cancer: A Prospective Multicenter Randomized Controlled Trial (AcCliMaT). J Clin Oncol Intracranial Efficacy of Crizotinib Versus Chemotherapy in Patients With Advanced ALK-Positive NonSmall-Cell Lung Cancer: Results From PROFILE 1014. J Clin Oncol Interventions for the management of malignant pleural effusions: a network meta-analysis. Cochrane Database Syst Rev 20
Granulocyte transfusions for treating infections in people with neutropenia or neutrophil dysfunction. Cochrane Database Syst Rev Comparing hospital and telephone follow-up for patients treated for stage-I endometrial cancer (ENDCAT trial): a randomised, multicentre, non-inferiority trial. BJOG Randomized Phase III Study Comparing Gefitinib With Erlotinib in Patients With Previously Treated Advanced Lung Adenocarcinoma: WJOG 5108L. J Clin Oncol Oral Ixazomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med Pazopanib plus best supportive care versus best supportive care alone in advanced gastrointestinal stromal tumours resistant to imatinib and sunitinib (PAZOGIST): a randomised, multicentre, openlabel phase 2 trial. Lancet Oncol Afatinib versus gefitinib as first-line treatment of patients with EGFR mutation-positive non-smallcell lung cancer (LUX-Lung 7): a phase 2B, open-label, randomised controlled trial. Lancet Oncol Evaluation of Scoring Systems and Prognostic Factors in Patients With Spinal Metastases From Lung Cancer. Spine (Phila Pa 1976) Effect of Chemoradiotherapy vs Chemotherapy on Survival in Patients With Locally Advanced Pancreatic Cancer Controlled After 4 Months of Gemcitabine With or Without Erlotinib: The LAP07 Randomized Clinical Trial. JAMA
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CANCER IN THE NEWS BACK TO TOP
“Scientists uncover potential trigger to kill cancer”. The paper published on this development is: “Identification of an activation site in Bak and mitochondrial Bax triggered by antibodies”, which was published only three days ago in Nature Communications. The researchers are now working with collaborators to develop their antibody into a drug that can access Bak inside cells
Daily low-dose aspirin may help combat cancer Overall, the link between aspirin and cancer risk – bowel cancer, in particular – definitely needs further consideration. But it needs to be clarified exactly which dose and frequency would give the best balance of effectiveness against safety, and for which population groups the benefits would outweigh the risks. Until this risk-benefit balance is better understood, no recommendation can be given for everyone to start taking daily aspirin to reduce cancer risk. Yin Cao, Reiko Nishihara, Kana Wu, et al. See: Population-wide impact of long-term use of aspirin and the risk for cancer. JAMA Oncology. Published online March 3 2016
Gene breakthrough promises 'bespoke' breast cancer treatment "Breast cancer treatment breakthrough after 'milestone' genetic discovery," says The Independent, about widely reported research investigating genetic mutations in people with breast cancer. The researchers took samples of cancer cells from 560 people with breast cancer (556 women and four men). They compared the DNA from the cancerous cells with DNA from normal cells. They found 93 genes that had mutated in the cancer cells and concluded that they could have caused normal tissue to become cancerous. They also found 12 genetic patterns linked with breast cancer. Science: http://www.nature.com/nature/journal/vaop/ncurrent/full/nature17676.html
Skin cancer cure hope for millions as major treatment breakthrough sees man's tumours disappear 'completely' Experts at the Fred Hutchinson Cancer Research Centre, in Seattle, Washington, have successfully treated a 53-year-old metastatic melanoma patient by combining two different types of immunotherapy for the first time. He had previously shown “little response” to treatment, and his skin cancer had begun to spread. But within weeks of the new double immunotherapy treatment, his tumours began to shrink, and then “disappeared completely”. Science: http://jem.rupress.org/content/early/2016/05/24/jem.20152021.abstract
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REPORTS, PUBLICATIONS AND RESOURCES
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A different ending: End of life care review: Care Quality Commission People from certain groups in society are experiencing poorer quality care at the end of their lives than others because providers and commissioners do not always understand or fully consider their specific needs. Some commissioners and providers might not be fulfilling their duties under the Equality Act 2010 as all public bodies have a legal duty to consider the needs of a range of equality groups when carrying out their day-to-day work. Health and care staff are not always having conversations with people early enough about their end of life care. This means they don’t have the opportunity to make plans and choices with their loved-ones about how and where they would prefer to die. We identified examples of good practice, but found that action is needed to make sure everyone has the same access to high quality, personalised care at the end of their lives, regardless of their diagnosis, age, ethnic background, sexual orientation, gender identity, disability or social circumstances. Overview report. This report provides the background to the review and the key findings: A different ending: Addressing inequalities in end of life care (Overview)PDF | 2.51 MB Good practice report. Examples of good practice in end of life care that we found through our review: A different ending: Addressing inequalities in end of life care (Good practice)PDF | 1.83 MB
ASCO Offers Guidelines on Managing Invasive Cervical Cancer in Different Resource Settings The document, developed by an expert panel and published in the Journal of Global Oncology, provides different recommendations depending on the resource setting. "The goal of our guideline is to recommend options in settings in which ideal treatment regimens may not be available," they write. For instance, in a basic setting, chemotherapy availability may be unpredictable, while in a resource-rich setting, bevacizumab should be available.
Achieving world class cancer outcomes: implementation plan NHS England has published Achieving World Class Cancer Outcomes: taking the strategy forward. This implementation strategy document sets out plans to deliver world class cancer services. The plan is designed to increase prevention, speed up diagnosis, improve the experience of patients and help people living with and beyond cancer.
Chemotherapy drugs ‘dose banding’ NHS England is intending to implement a national system of ‘dose banding’ to reduce variation in chemotherapy drug doses. Dose banding has been happening at a local level for some ten years but the practice remains inconsistent. By implementing a national approach, NHS England expect that
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more than 90% of chemotherapy doses will be prescribed and administered in accordance with bandings by March 2018.
On The Brink: The Future of End of Life Care. Macmillan Cancer Support; 2016. This report highlights a range of widespread failures in care for dying people. It reveals that some people at the end of life are unable to get access to social care for help with everyday tasks such as washing and changing clothes, and many families are being left without professional advice on how to care for their dying relative.
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TRAINING & NETWORKING OPPORTUNITIES, CONFERENCES, EVENTS BACK TO TOP
4th ESO-ESTRO Masterclass in radiation oncology 19-23 November 2016 / Prague, Czech Republic Deadline to apply: 14 May 2016
Hematological Malignancies 31 August -3 September 2016 / Vienna, Austria Early registration deadline: 1 June 2016 Palliative care and Radiotherapy - a course on prognosis, symptom control, reirradiation, oligometastases â&#x20AC;&#x201C; NEW 8-10 September 2016 / Brussels, Belgium Early deadline: 8 June 2016 Basic Treatment Planning 9-13 September 2016 / Cambridge, UK Early deadline: 9 June 2016 Physics for modern radiotherapy Joint course for clinicians and physicists 11-15 September 2016 / Athens, Greece Early deadline: 13 June 2016 Advanced Treatment Planning 14-18 September 2016 / Cambridge, UK Early deadline: 14 June 2016 Imaging for Physicists 18-22 September 2016 /Florence, Italy
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Early Deadline: 20 June 2016
Summer 2016 UNDERGRADUATE TRAINING FOR MEDICAL STUDENTS Medical science summer school oncology 4 - 15 July 2016 / Groningen, The Netherlands ESO-ESSO-ESTRO multidisciplinary course in oncology 29 August - 9 September 2016 / Poznan, Poland
6th ICHNO International conference on innovative approaches in head & neck oncology 16-18 March 2017 Barcelona, Spain Abstract submission deadline: 12 October 2016 Early registration deadline: 26 October 2016
JOINT AND SCIENTIFIC COLLABORATION
6th World Congress of Brachytherapy 27-29 June 2016 San Francisco, USA Jointly organised by ABS, GEC-ESTRO, ALATRO, CBG-CAR, JASTRO, AROI, IBS & ABG Early registration deadline: 27 May 2016
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ECCO 2017 European Cancer Congress 27-30 January 2017, Amsterdam, The Netherlands Download the advance programme > Abstract submission now open > Abstract submission deadline: 25 August 2016. Early Registration Deadline: 27 June 2016
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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. 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
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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?
Do you need a literature search carried out?
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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 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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