NCRI Cancer Conference 2013

Dr O'Keefe talks to ecancertv at the UK's National Cancer Research Institute ( NCRI ) 2013 meeting about study comparing US and South African diets and colon cancer risk in men of African origin. Geographical and migration epidemiological studies, backed up by experimental studies, have produced overwhelming evidence that diet drives colon cancer risk, with high intakes of meat and fat increasing risk, and high consumption rates of fiber rich foods, such as grains, fruits and vegetables, reducing risk. To test the hypothesis that cancer risk is determined by the effect the diet has on the composition and function of the microbiota to produce metabolites that either promote mucosal health or are inflammatory and neoplastic, they conducted studies in populations of high and low risk, namely African Americans who have the highest risk in the USA, and rural Africans, who rarely get the disease, and confirmed that high meat and fat intakes in Americans were associated with increased mucosal proliferation rates – a biomarker of cancer risk, while high fibre African diets were associated with low proliferation rates. Simultaneous measurement of the microbiota and metabolome showed dramatic differences in the microbiota composition and function. The structure of the African colonic microbiota was considerably more robust, with amplification of the bacterial groups associated with complex plant carbohydrate degradation and butyrate production. Targeted analysis confirmed higher numbers of butyrate-producing bacteria and butyrate, which has profound anti-neoplastic properties in experimental models. In contrast, secondary bile acid producing bacteria and their products, which have carcinogenic properties, were higher in African Americans. Most recently, the team demonstrated that dietary switch between these two populations produces reciprocal changes in the microbiome, metabolome, and mucosal biomarkers of risk within 2 weeks, leading to the conclusion that modification of the diets of westernized populations to contain high fiber (>45g/d) foods, such as grains and beans, together with lower intakes of animal fats, can be expected to have an immediate effect on cancer risk.

Prof Ponder talks to ecancertv at the UK's National Cancer Research Institute ( NCRI ) 2013 meeting where he received the Lifetime Achievement award. Prof Ponder's first major success in genetics was the linkage of medullary thyroid cancer to chromosome 10, which led to a test for genetic susceptibility to this rare disease. In the late 1980s he moved on to study breast cancer; the international consortium he established in breast cancer genetics led directly to the discovery of BRCA1 and BRCA2. Later still he was involved in the first genome-wide association scans (GWAS). Results from these, however, have been disappointing: for example, even with GWAS we have been able to explain less than 20% of the genetic variation in breast cancer risk. Ponder ended his plenary lecture by suggesting that combining genes into networks might help explain some of this missing heritability of breast cancer.

Prof Bauld talks to ecancertv at the UK's National Cancer Research Institute ( NCRI ) 2013 meeting about the ‘end game' for tobacco control in the UK, and key priorities for science and policy to reduce smoking Smoking prevalence in the UK has declined steadily in recent years but one in five adults still smoke. A current focus for tobacco control science and policy is to work towards reducing prevalence to 5% or less in the coming decades. The session she chaired focussed on new evidence about the key drivers for prevalence reduction including: using price measures to counteract the activities of the tobacco industry; addressing smuggling; the EU tobacco products directive and evidence on health warnings and standardised packaging; point of sale interventions; and priorities for reducing the uptake of smoking amongst young people. The session was for preventative medicine, behavioural science and public health researchers, practitioners and policy makers.

Prof John Yarnold talks to ecancertv at the UK's National Cancer Research Institute ( NCRI ) 2013 meeting about optimial radiotherapy for breast cancer. Breast cancer is as sensitive to radiation fraction size as normal tissues, 10-year follow-up of clinical trials, including the UK START trials, has shown. This means it makes sense to give early breast tumours fewer, larger doses of radiation, rather than more, smaller doses. The result has been to switch from a standard five-week schedule of 25 fractions to a more convenient three-week schedule delivering 15 fractions of 2.7 Gy. Current 15-fraction schedules are standard of care for local-regional radiotherapy in the UK, but 15- or 16-fraction regimens are unlikely to represent the lower limit. It is now important to find out if there is wide variation between breast cancers in their sensitivity to different levels of radiation. If there is a lot of variation between cancers, it highlights the need to identify tests to exploit this variation for the benefit of future patients. By the end of this decade, research could bring about a regimen of local-regional radiotherapy with as few as five fractions for women with early breast cancer. John Yarnold is Professor of Clinical Oncology at The Institute of Cancer Research, London, and Honorary Consultant at the Royal Marsden NHS Foundation Trust.

Dr Omid Farokhzad talks to ecancertv at the UK's National Cancer Research Institute ( NCRI ) 2013 meeting about the use of polymeric nanoparticles for cancer drug delivery. A variety of organic/inorganic materials are utilised to generate nanoparticles for drug delivery: Polymeric nanoparticles, dendrimers, nanoshells, liposomes, nucleic acid based nanoparticles, magnetic nanoparticles, and virus nanoparticles. Two most commonly used systems are polymeric nanoparticles and liposomes. Controlled release polymer technology impacts every branch of medicine: Ophthalmology, pulmonary, pain medicine, endocrinology, cardiology, orthopedics, immunology, neurology and dentistry, with several of these systems in clinical practice such as Atridox, Lupron Depot, Gliadel, Zoladex, Trelstart Depot, Risperidol Consta and Sandostatin LAR. The market of controlled release polymer systems extended beyond drug delivery is estimated at $100 billion and are used by over 100 million people a year. Polymeric nanoparticles deliver drugs in the optimum dosage over time, increasing the efficacy of the drug, maximising patient compliance and enhancing ability to use highly toxic, poorly soluble, or relatively unstable drugs. These systems can also be used to co-deliver two or more drugs for combination therapy. The surface engineering of these nanoparticles may yield them ‘stealth’ to prolong their residence in blood and the functionalisation of these particles with targeting ligands can differentially target their uptake by a subset of cells, increasing their specificity and efficacy. The successful clinical translation of therapeutic nanoparticles requires optimisation of many distinct parameters including: Variation in the composition of the carrier system, drug loading efficiency, surface hydrophilicity, surface charge, particle size, density of possible ligands for targeting, etc., resulting in a large number of potential variables for optimisation which is impractical to achieve using a low throughput approach. Recently, combinatorial approaches have been developed to precisely engineer nanoparticles and screen multiple nanoparticle characteristics simultaneously. Our goal is to review efforts in design and optimisation of polymeric nanoparticles for medical applications, which formed the foundation for the clinical translation of the first-in-human targeted and controlled-release nanoparticles (BIND-014) for cancer therapy.

Dr Lesley Anderson talks to ecancertv at the UK's National Cancer Research Institute ( NCRI ) 2013 meeting about a study looking at the changing profile of HPV infection and resultant disease now that the UK has introduced an HPV vaccine. This study aimed to determine the prevalence of HPV infection among screening age women prior to vaccination and determine HPV types associated with cervix disease. HPV positivity was investigated using the Roche Cobas 4800 in 5557 eligible Liquid Based Cytology (LBC) samples from women of screening age in Northern Ireland and 2048 samples of cervical pathology collected prospectively. LBC samples revealed a crude age standardised prevalence of high risk HPV of 17.4% in screening age women in Northern Ireland. The highest rate (42.5%) was in those aged 20-24. HPV prevalence by main subtypes were: HPV 16 (5.3%) 31 (2.5%) 51 (2.2%) 18 (1.7%). For cervical pathology prevalence of HPV was 64.7% overall, increasing from 48.1% of CINI, 65.7% of CINII, 81.3% of CINIII to 89.1% of cervical squamous cell carcinomas (SCC). The majority of SCC's tested positive for HPV16 or 18 (91.2% of HPV positive samples). HPV positivity was found in 92.9% microinvasive SCC, 50% of adenocarcinomas, 66.7% adenosquamous carcinomas, 88.2% cervical glandular intraepithelial neoplasia and 29.1% koilocytosis. The number of genotypes detected varied across pathology grade, On average 2.5 genotypes where detected per positive sample. A trend was identified that CIN I had the lowest percentage (66.0%) of single genotypes. On average 91.8% of all cancerous samples containing only one HPV genotype. The most frequent single genotypes found in cancerous samples were HPV16, HPV18, HPV45, HPV31, HPV39 and HPV52. For SCC samples not testing positive for HPV16 or HPV 18, five samples tested positive for a single HPV 31, HPV 39, HPV 45 or HPV 52 genotype, which may have implications for vaccine cross protection of non-target genotypes as these types are common in women with normal cervical pathology.

Dr Lesley Anderson talks to ecancertv at the UK's National Cancer Research Institute ( NCRI ) 2013 meeting about a study looking at the effects of prostate cancer treatment comparing the Republic of Ireland with Northern Ireland, UK. There are differences in services such as testing, leading to 30% more diagnosis in the ROI than Northern Ireland; in some cases overdiagnosis. The team carried out a postal survey of men diagnosed with prostate cancer, receiving 3300 replies with very useful quality of life information leaving us in a better position to inform men about the treatment options associated with prostate cancer.

Dr Robert Thomas talks to ecancer at the 2013 NCRI Cancer Conference in Liverpool about a polyphenol food supplement that has been shown to slow the spread of prostate cancer. Polyphenol rich foods such as pomegranate, green tea, broccoli and turmeric have demonstrated anti-neoplastic effects in cell lines and animal models, including anti-angiogenesis, pro-apoptotic and reduced proliferation. Some have been investigated in small phase II studies. This study found a statistically significant, favourable effect on the percentage rise in PSA in this cohort of men with prostate cancer. Future trials will look at the longer term clinical effects and the benefits for men receiving ADT.

Dr Jane Seymour gives a comment to ecancertv at the UK's National Cancer Research Institute ( NCRI ) 2013 meeting on a session which she chaired looking at the latest in treatment decision making for oncologists and patients, screening, and palliative care. The session included: - Modafinil for fatigue in lung cancer: multicentre, randomised, double-blinded, placebo-controlled trial: effect, dose response and patient satisfaction - Results from the UNBIASED study (UK – Netherlands – Belgium International SEDation study) : reported practices of physicians and nurses in three European countries - An all-Ireland population-based study of past and current physical and psychological side-effects following prostate cancer treatments - Reduction in interval cancer rates following the introduction of two-view mammography in the UK breast screening programme - Clinical implications of a prostate cancer risk SNP profile in 2 treatment cohorts - Over or under treatment? A systematic review and meta-analysis of factors determining change of management in active surveillance for localised prostate cancer - Obesity and the outcome of young breast cancer patients in the UK: The POSH study

Dr Gerard Evan talks to ecancer at the 2013 NCRI Cancer Conference in Liverpool about methods for discovering new targets for treating cancer and the continuing move towards a more personalised approach to treatment.

Dr Andy Hall talks to ecancer at the 2013 NCRI Cancer Conference in Liverpool about the development of biobanks and collection of primary material in rare tumours. Dr Hall discusses heterogeneous tumours and the importance of access to primary material. With this access there can be a greater understanding of the tumour's biology, mutations and potential targets and biomarkers.

Dr Ruth Swann talks to ecancer at the 2013 NCRI Cancer Conference about breast cancer survival rates and the largest prospective observational study that examined the relationship between diet and lifestyle and breast cancer recurrence and survival rates of patients in the UK. The DietCompLyf study showed a significant inverse association between pre-diagnosis phytoestrogen consumption and possession of breast cancer risk factors. The data from the study will provide the necessary evidence base on which to test dietary and lifestyle recommendations for breast cancer patients, the overall aim of which is to reduce breast cancer recurrence rates.

Dr Lisa Coussens talks to ecancer at the 2013 NCRI Cancer Conference in Liverpool about inflammation and cancer and how this can be used in the tumour microenvironment. By studying transgenic mouse models of skin, lung, breast and pancreas cancer development, Dr Coussens lab found that adaptive leukocytes differentially regulate myeloid cell recruitment, activation, and behaviour, by organ-dependent mechanisms. This has been translated into a recent clinical trial involving triple negative breast cancer.

Dr Chris Gallagher talks to ecancer at the 2013 NCRI Cancer Conference in Liverpool about the PETROC study. The trial is a meta analysis of phase III trials of post operative intraperitoneal chemotherapy in epithelial ovarian cancer, fallopian tube and primary peritoneal cancer. In the 853 patients that participated, with 6 years follow-up, there was a reduction of 16% in risk of progression, 17% in risk of death, and increased median progression free (20 to 25 months),and overall (51 to 62 months )survival. PETROC/OV21 is designed to investigate women not able to be optimally debulked at primary surgery who have had primary IV chemotherapy and optimal interval debulking followed by IVor IP treatment, with dose paclitaxel plus carboplatinor cisplatin. The study reached the conclusion that intraperitoneal chemotherapy after interval debulking surgery is feasible and safe.

Dr Bernd Pichler talks to ecancer at the 2013 NCRI Cancer Conference about combination of PET/MRI, which allows for molecular and functional imaging and information to be gather analysed together.

Dr Daniel Rea talks to ecancer at the 2013 NCRI Cancer Conference in Liverpool about the aTTom study. In patients with early breast cancer, tamoxifen was given for 5 years after surgery for ER-positive early breast cancer. This reduced recurrence and breast cancer mortality and was more effective than treatment for shorter durations. It has been uncertain what advantage there may be to extending tamoxifen treatment to 10 years. aTTom confirmed findings of the complementary International ATLAS study that, continuing tamoxifen to year 10 rather than just to year 5 produces further reductions in recurrence and breast cancer deaths. The proportional reduction in recurrence was unaffected by age or nodal status. Benefits from continuing tamoxifen treatment beyond year 5 emerge only after 7 years from start of treatment for recurrence and 10 years for mortality.

Julie Cornish and Andy Torrance discuss the collaborative experience of recent trainee-led surgical trials and first-hand experience of the surgical research collaborative infrastructure. The HART trial s a randomised controlled trial that is currently being developed by the Welsh Barbers Research Group. The aim of the trial is to compare the incidence of incisional hernias for two methods of wound closure for patients undergoing surgery for colorectal cancer. http://www.welshbarbers.org/ http://wmresearch.org.uk/ http://www.asit.org/

Dr Ellen Copson talks to ecancer at the 2013 NCRI Cancer Conference in Liverpool about the rising rates of obesity in patients with early breast cancer. Previous studies have shown that this leads to a poorer prognosis than non-obese patients and that host factors, tumour pathology and treatment issues have been suggested as possible factors. The study concluded that obesity at diagnosis is associated with inferior survival in young breast cancer patients. The data confirms that obesity is associated with biologically adverse tumours and more obese patients receive sub-optimal chemotherapy than healthy weight patients.