Oncology News January/February 2016

Oncology

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Volume 10 Issue 6 • January/February 2016 • www.oncologynews.biz

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The therapeutic potential of targeting brain tumour metabolism through LDHA Mapping tumour tissue: quantitative maps of histological whole slide images Bridging the gap in Breast Cancer surgical planning and aesthetic outcome prediction: The European Picture Trial Review of transoral robotic surgery

ON THE COVER – The 11th Palliative Care Congress is coming in March 2016 - see page 180 for details

FROM THE EDITOR

Ideas about Cancer – Hypotheses as the Essential Basis of Advancement

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Denys Wheatley Editor

REFERENCES 1. Wheatley DN. Editorial: The fundamental basis of cancer – is there a general theorem on which to build? Oncology News 2014;9(2):40.

2. Weinberg RA. Coming full circle – from endless complexity to simplicity and back again. Cell 2014;157:267-71.

3. Sonneschein C and Soto A. The Society of Cells: Cancer and the Control of Cell Proliferation. Springer, New York. 1999.

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he fundamental cause of carcinogenesis is a loss of growth control of cells in tissue such that their proliferation rate exceeds, however small, that expected in normal circumstances. Some are more susceptible to change than others for reasons that are, as yet, difficult to explain. While tumours arising in a particular tissue, such a liver parenchyma, might look similar in many cases, each is unique. And even if they arise through some similar set of mutations (particularly where there is inherited genetic susceptibility), the environment may differ in each case, leading to different patterns of outgrowth and responsiveness to treatment.

Cancer can arise anywhere, at any time, and be caused by genetic, epigenetic and other changes.

We have discussed on a previous occasion [1] that apparently normal cells may show some kind of “anti-social behaviour” when displaced into an inappropriate environment. Although there could be some kinds of underlying mechanisms in carcinogenesis, there are perhaps hundreds or thousands of factors or mitigating circumstances involved, of which different sets under different conditions lead to a vast array of malignant transformations. Conclusion – there is no single cause of carcinogenesis and we are still a long way from reaching any synthesis regarding it.

Whether a cancer will invade or not is also indeterminate; although we can give a probability, some types of tumours being more prone to do so than others, the outcome is uncertain in any particular instance. Whether a cancer will undergo complete spontaneous or induced remission is also unpredictable, and whether we can prevent some cancers arising in the first place can only be given a probability (the reduction in risk). The latter will depend on genetic disposition, level of exposure to carcinogens and the metabolic status of the individual. As to whether he or she might succumb quickly or slowly to a cancer that has developed will depend on a vast number of factors, not least the frame of mind.

Conclusion – while we may be aware of some of the general characteristics of tumours, we have little real insight into their development, behaviour and responsiveness. Therefore, making any predictions and generalisations about many aspects of cancer are fraught with danger, we have to make some of these daily. To get to grips with cancer, there is a need to focus on specific areas because of its great diversity. And as scientists and doctors, we have to keep searching for answers to many questions if we are to gain better control over tumours. Inevitably there can be thousands of questions related to the

problems discussed above. We can only progress if we make rational hypotheses, test them efficiently in the laboratory and clinic, refine them if they hold some water, and eliminate them when they are unsubstantiated. Hypotheses can arise in two main ways, by building on previous knowledge, or by lateral thinking, where no obvious correlation had previously seemed to exist. Linus Pauling’s dictum about advancing our knowledge by experimentation was the remark that “you need lots of hypotheses and some means of selection” (i.e. some have more merit in pursuing than others). Framing a hypothesis takes a lot of skill before any experiment; so often in hindsight we realise we asked the wrong question or framed it poorly.

For this reason, and having demitted editorship of other cancer journals, I am now creating a new one called Cancer Hypotheses, akin to Medical Hypotheses founded by my late colleague David Horrobin and published by Wiley, but clearly in a specific field. Since all experimental work, laboratory investigations and clinical trials should be based on a hypothesis (other than exercises that amount to little more than data collection), every cancer paper to communicate new findings should be eligible for submission! While this would open up the journal to everyone in the field of cancer, the original intent is primarily to be a forum for those who want to discuss broader rather than narrower issues, such as a possible molecular basis of cancer [2] or ideas about field theories [3]. Where attempts have been made to make a synthesis of current knowledge, review articles that bring many viewpoints together would be welcome. However, since some people can have new ideas that do not seem to emerge from existing knowledge, of thinking outside the box, we should remember the old adage that perhaps “today’s crazy idea might become the received wisdom of tomorrow”. If a piece of experimental work throws up something truly original in this way, then Cancer Hypotheses would certainly welcome them, provided enough circumstantial evidence could be presented to give it some resonance – some “ring of truth”. Equally, some new finding that calls for a thorough reappraisal of an extant, but perhaps controversial, hypothesis is just the right sort of material for the journal.

I welcome contributions from all who have contributed to and/or read Oncology News, and also any of your colleagues who might have interesting ideas and data that would fit our remit. The new journal will also be published by McDonnell Mackie.

Volume 10 Issue 6 • January/February 2016

CONFERENCE NEWS Are you organising an annual meeting or conference which you would like to tell our readers about?

Or would you like to write a report on a meeting or conference of particular interest?

If so, contact Patricia McDonnell at Oncology News on T/F: +44 (0)288 289 7023, E: patricia@oncologynews.biz

BAHNO Annual Scientific Meeting 2016 – Joint meeting with Allied Health Professionals Date: 13 May 2016. Venue: London, UK.

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his year’s British Association of Head & Neck Oncologists Annual Scientific Meeting will be on the topic of ‘Head and neck cancer treatment – at what cost?’.

We are running a new format for the meeting this year in conjunction with our allied health professional colleagues. The programme will include some joint sessions, as well as some parallel sessions for the AHPs – aimed at increasing the participation of the different disciplines involved in the management of head and neck cancer.

We are lucky to have a very distinguished speaker – Professor Joseph Helman from the University of Michigan – to deliver the

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Blair Hesketh Lecture. The debate is going to be on the topic of this house believes that the NHS can afford transoral robotic surgery. We have an excellent line up of speakers, whom we have pitted against their usual stances on this topic, hopefully leading to a very interesting debate.

Please note the change in the date of the meeting this year – it is not the usual last Friday in April to avoid clashing with several other conferences.

For further information visit: http://bahno.org.uk

International Society of Pediatric Neuro-Oncology Conference 2016 Date: 12-15 June 2016. Venue: Liverpool, UK.

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SPNO meetings have become the pre-eminent event in the field of Central Nervous Tumours in children and young people.

The International Symposium on Pediatric Neuro-Oncology (ISPNO) is the major biennial global meeting of the multidisciplinary international community of professionals involved in the research, diagnosis, treatment and rehabilitation of infants and children with brain tumours. ISPNO has enjoyed consistent growth since its first meeting in 1986 with over 800 delegates drawn mostly from oncology, neurosurgery and radiation oncology.

The 17th ISPNO in 2016 will mark the second meeting of ISPNO in the UK, returning to England for the first time since the London meeting in 2002. This year’s conference will be hosted in the vibrant and cosmopolitan city of Liverpool. It will take place within the ACC Liverpool which is equipped with fantastic facilities to host a conference of this size. Liverpool City itself has various shops, tourist attractions and restaurants within the vicinity of the ACC Liverpool. This provides delegates with plenty of options as to how they spend their downtime during the conference period.

Throughout the entire symposium, attendees will engage in dialog regarding new surgical treatments, innovative research and advances in pediatric neuro-oncology in a dynamic and interactive forum designed to significantly expand the knowledge base of attendees and further enhance overall patient care worldwide.

Who should attend?

The 17th ISPNO welcomes attendees from the following list:* 1. Regional and International Delegates from Developed and Developing Countries 2. Leading Decision-Makers and Researchers in the Field of NeuroOncology

Volume 10 Issue 6 • January/February 2016

3. Sub-specialties such as: Neuro-oncologists, Neurosurgeons, Radiation Oncologists, Developmental and General Pediatricians, Neurologists, Neuroscience Researchers, Late Effects Specialists, Neuro-Pathologists, Neuro-Radiologists, Endocrinologists, Rehabilitation Specialists, Nurses, Allied Health Groups such as Psychologists and Social Workers *This list is not exhaustive and is intended as a guide only.

The 17th ISPNO encourages all professionals dedicated to the care of children with CNS tumours to benefit from this valuable opportunity to engage with experts, gain insights and establish new collaborations from the enriching plenaries, poster program and more.

Registration for this event opens 4th January with abstract submissions open up until the 19th February 2016.

Visit: www.ISPNO2016.com

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CONFERENCE NEWS

The 11th Palliative Care Congress Date: 9-11 March 2016. Venue: Glasgow, UK.

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he biennial Palliative Care Congress is will have its eleventh meeting at the Scottish Exhibition and Conference Centre in Glasgow, from 9-11 March 2016.

The event is a joint collaboration between the Association for Palliative Medicine and the Palliative Care Research Society and brings together practitioners involved in palliative care from across the specialty – doctors, nurses, researchers, social workers, bereavement officers and other allied health professions, from whatever contexts they practice – NHS, charity, hospital, day units.

Congress is a great opportunity to meet with others, share practice, understand what the national perspective is and think how new ideas could affect local practice.

The Organising Committee decided to centre the emphasis for this Congress on holism. Palliative care has always stated that holism, i.e. treating people as people and addressing their medical, social, psychological and spiritual needs, is at the heart of the movement. The challenge in the current health environment, where evidence and cost effectiveness are called for, is for palliative care to define or redefine how holism works and why it is still the right focus for care for those with life limiting illness.

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To help us do this we have invited speakers who are engaging and challenging but also well recognised within their field. Professor Arthur Frank will be speaking on the challenge to health care of survivorship. He will be expanding ideas first put forward in his land mark book ‘The Wounded Storyteller’. Rev John Bell will be talking on spiritual care within health. John is guardian of the Iona Community and a frequent speaker on Radio 4.

As well as our headline speakers we will be hosting posters and oral presentations of the latest research within the field, as well as updates on the latest in symptom control and a range of lectures, symposia, masterclasses and workshops.

The program is packed, varied and has something to challenge, stretch and make each delegate think. We look forward to learning with you in Glasgow.

For the latest information, please visit our website www.pccongress.org.uk Derek Willis, Chair, The 11th Palliative Care Congress.

John Fitzpatrick Irish Prostate Cancer Conference 2016 Date: 21-22 April 2016. Venue: Dublin, Ireland.

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ast April’s inaugural John Fitzpatrick Irish Prostate Cancer Conference was a significant success with over 300 delegates in attendance.

For 2016, this multidisciplinary meeting will once again bring together leading Irish and UK health care professionals with an international faculty of oncology and urology experts from Europe, North America and Australia. The meeting will provide participants with the opportunity to facilitate best practice by discussing and disseminating the latest trends and developments in treatment and therapy whilst also affording the opportunity to network with peers.

Professor John Fitzpatrick, distinguished academic urologist, Emeritus Professor of Surgery at the University College Dublin (UCD) School of Medicine & Medical Science, former Consultant Urologist and Chairman of the Division of Surgery at Mater Misericordiae University Hospital (MMUH), Dublin, and Head of Research at the Irish Cancer Society, sadly passed away in May 2014.

He was an academic clinician / scientist of distinction, advancing surgical techniques and urology training throughout his career.

Professor Fitzpatrick developed enduring professional connections across the UK and Europe, North America, and Australasia earning

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a reputation on the global stage seldom before afforded to an Irish surgeon.

Professor’s research interests were wide and varied, including Prostate Cancer. He was a founding member of the Prostate Cancer Research Consortium, a groundbreaking collaboration between UCD, TCD, RCSI, DCU, and their affiliated teaching hospitals. His publications in the Prostate Cancer arena spanned the entire spectrum from the bench to the bedside. He performed open and robotic surgeries in a career of over 1,000 radical prostatectomies.

Professor Fitzpatrick’s immeasurable contribution to the understanding and management of prostate cancer will be forever remembered at this new annual meeting, the John Fitzpatrick Irish Prostate Cancer Conference.

Registration will be open to medical professionals working in the urology and cancer care communities; consultants; surgeons; nurses; scientists; registrars; researchers and trainees. The programme will be available shortly at www.irishprostatecancerconference.weebly.com Please note this meeting has submitted an application for CPD Credits from the RCSI Faculty of Radiologists.

Volume 10 Issue 6 • January/February 2016

AWARDS AND APPOINTMENTS

The British Institute Of Radiology (BIR) And Philips Healthcare Announce Winners Of Annual Awards For Trainees And Students The BIR/Philips Trainee Award for Excellence The purpose of the Trainee Award for Excellence is to foster the development of multidisciplinary educational resources by, and for, trainees.

The winner of this award for 2014 was Dr Mark Rodrigues, Dr Zeshan Qureshi and their team from the Royal Edinburgh Infirmary for their guide to radiographic appearances and was presented at the BIR trainee event “The future of radiology” in November 2015. The guide is aimed at providing an overview of radiology to medical students and junior doctors, with particular emphasis on how to approach plain x-rays and highlighting common/important abnormalities using high quality images. It is written by radiology, orthopaedic and paediatric registrars, with consultant input, and reviewed by medical students (See image right).

Dr Zeshan Qureshi (left) with BIR president Dr David Wilson.

The BIR/Philips Student Travel Bursary BIR/Philips Student Travel Bursary provides £250 to attend a relevant training event. The student bursary aims to offer educational opportunities to students of any discipline to access opportunities which otherwise wouldn’t be available without this cash prize.

The winner of this award for 2014 was Dr Cherry Sit, from King’s College Hospital who used the award to help her attend the British Nuclear Medicine Society conference in 2015. (See image right). The award was presented at the BIR Annual Congress on 5 November 2015.

Both awards will be judged by the BIR Education Panel, which will include a representative from Philips.

Dr Cherry Sit (centre) with Arshad Mohammed (Modality Sales Specialist, Philips Healthcare) and Dr David Wilson, President BIR.

Closing date for applications for both awards: 28 February 2016.

Apply at: www.bir.org.uk/professional-resources/prizes,-awards-and-bursaries/ Only trainee or student members of the BIR are eligible to apply for both these awards.

Cancer Hypotheses This new open access journal will appear in early 2016 as a joint venture between BioMedES UK (www.biomedes.co.uk) and McDonnell Mackie (www.oncologynews.biz).

The journal’s main purpose is to act as a forum where hypotheses old and new can be aired and discussed. Every cancer study, experimental or clinical, should be hypothesisbased, but we could not handle papers on all of them! We will focus on those that are truly original and have some novel data to support them. Researchers are often reluctant to publish new ideas about cancer, especially if seem “way-out”. However, submissions of this kind are welcome; some may well have an element of truth in them, and we all know that there are no “fundamental” theorems of cancer.

The journal will be based on the author-pays model, but this will not be applied to any paper accepted up to the end of July 2016. Thereafter a charge will be made, but it will be much less than that currently being levied by most other (cancer) journals.

Volume 10 Issue 6 • January/February 2016

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Contents

Volume 10 Number 6 • January/February 2016

178 Editorial 179 Conference News

Previews and reports from the conference scene.

181 Awards & Appointments 183 Neuro-oncology – The therapeutic potential of targeting brain tumour metabolism through LDHA

Carla Valona, Portsmouth, UK

188 Cancer Image Analysis – Mapping tumour tissue: quantitative maps of histological whole slide images

Jakob Nikolas Kather, Cleo-Aron Weis, Frank Gerrit Zöllner, Manheim, Germany and Constantino Carlos Reyes-Aldasoro, London, UK

191 Book Reviews 192 Breast Cancer – Bridging the gap in Breast Cancer surgical planning and aesthetic outcome prediction: The European Picture Trial

Mo R Keshtgar, London, UK, Maria J Cardoso, Portugal and Gerrit-Jan Liefers, The Netherlands

194 Head & Neck Cancer – Review of transoral robotic surgery

Giri Wijayasingam and Mriganka De, Derby, UK

196 Journal Reviews 198 Diary

Listing of meetings, courses and conferences, both UK and

www.oncologynews.biz Visit today to: Subscribe for free and read the digital online edition of the magazine Search our extensive online diary of upcoming courses and conferences Access the archive of articles from previous editions of Oncology News

BRAIN TUMOURS KILL MORE CHILDREN AND ADULTS UNDER THE AGE OF 40 THAN ANY OTHER CANCER

international.

199 Courses & Conferences 200 News Update Details of the latest developments and news from the industry and charities.

Oncology News is published by McDonnell Mackie, 88 Camderry Road, Dromore, Co Tyrone, BT78 3AT, N Ireland.

Publisher: Patricia McDonnell • Web: www.oncologynews.biz

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Volume 10 Issue 6 • January/February 2016

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The therapeutic potential of targeting brain tumour metabolism through LDHA Cara Valvona, BSc, Final year PhD student, Brain tumour research centre, University of Portsmouth, UK. Correspondence to: cara.valvona@port.ac.uk

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esearch into targeting tumour metabolism as a therapeutic approach has increased since it was added to the list of hallmarks of cancer in 2011 [1].

Lactate dehydrogenase A (LDHA) is a key enzyme involved in the Warburg effect, a metabolic pathway which appears to be universal in tumours, including primary brain tumours. Most studies on LDHA have been conducted in noncentral nervous system tumours, and although studies into inhibiting LDHA as a therapeutic target for brain tumours, presented in brief here, have shown promise in reducing tumour growth and migration, they are few in number and currently no LDHA inhibitors are available for clinical use.

Lactate dehydrogenase metabolism Lactate dehydrogenase (LDH) enzymes increase the rate of the reaction depicted in figure 1. LDHA has a high affinity for pyruvate, preferentially converting pyruvate to lactate and NADH to NAD+ whereas LDHB has a high affinity for lactate, preferentially converting lactate to pyruvate and NAD+ to NADH [2].

is available, a characteristic termed aerobic glycolysis or the Warburg effect, first observed

by Otto Warburg in the 1920s [4].

Brain metabolism is complex and able to respond dynamically to changes in blood glucose and lactate concentrations [5]. In mouse and rat brains, LDHB mRNA expression is predominant with the exception of strong LDHA expression in the hippocampal regions CA1, CA2 and CA4, the ventromedian hypothalamic nucleus, and the dorsal raphe nucleus as well as moderate expression in the cerebral cortex [6]. However, studies have shown that the energy needs of the brain changes over a lifespan. The human brain uses high levels of aerobic glycolysis during foetal growth and development but then switches to oxidative phosphorylation which is seen predominantly in the adult brain [7].

LDHA and tumour malignancy LDHA over-expression is a common characteristic of cancers; it promotes elevated lactate concentrations which have been shown to predict tumour malignancy, recurrence, survival and metastasis in many types of cancer patients [3,8]. LDHA is also associated with other poor prognostic factors including tumour hypoxia [9], angiogenesis [10], proliferation and glucose uptake [11] as well as resistance to chemotherapy [12] and radiotherapy [13].

Deregulation of LDHA in brain tumours

Figure 1: The reaction catalysed by lactate dehydrogenase (LDH).

Adapted from Valvona et al [3]. LDH catalyses the reversible conversion of pyruvate and NADH to lactate and NAD+.

Under normal physiological conditions, pyruvate is used to fuel oxidative phosphorylation and ATP production. However, when oxygen becomes scarce, ATP is produced using anaerobic glycolysis, which requires LDHA to convert pyruvate to lactate (Figure 1). Although it is less efficient at producing ATP, anaerobic glycolysis is 100 times faster than oxidative phosphorylation. Cancer cells upregulate LDHA to convert pyruvate to lactate in order to generate ATP via glycolysis even when oxygen Volume 10 Issue 6 • January/February 2016

LDHA has long been known to be regulated by major transcription factors; hypoxiainducible factor 1 (HIF1) and c-Myc [9, 14]. HIF1 is often stabilised in brain tumours [15] and associated with a significantly poorer survival rate [16]. C-Myc expression is also often deregulated in brain tumour cells, including the medulloblastoma (MB) subgroup with the worst outcome (Group 3) [17], and has been shown to transform rat fibroblasts by up-regulating LDHA [14]. More recently forkhead box protein M1 (FOXM1) and Kruppel-like factor 4 (KLF4) have been shown to regulate LDHA transcription [18, 19]. FOXM1 is a marker of poor prognosis in MB [20] and regulates glioma tumourigenicity [21] whereas KLF4 is also suppressed in MB [22] and mutated in meningioma [23]. Like many enzymes, LDHA post-transcriptional activity is regulated by phosphorylation and acetylation of amino-acid 183

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Figure 2. Schematic showing processes that are reportedly affected by lactate dehydrogenase A (LDHA).

Adapted from Valvona et al [3].

LDHA has been reported to be involved with the processes listed in the orange box. LDHA has also been reported to indirectly influence the processes listed in the red box via aerobic glycolysis and lactate production.

Inhibition of LDHA obstructs aerobic glycolysis and the processes listed in the red and orange boxes. Cancer cells are then forced to use oxidative phosphorylation and pyruvate enters the mitochondria. This leads to reactive oxygen species (ROS) generation and apoptosis (green box).

residues. The oncogenic receptor tyrosine kinase FGFR1, expressed in meningioma and glioma [24], has been shown to directly phosphorylate LDHA at Y10 and Y83 [25].

Y10 phosphorylation of LDHA promotes active, tetrameric LDHA formation whereas phosphorylation of Y83 promotes NADH substrate binding [25]. Together these studies suggest that LDHA expression is commonly deregulated in a range of brain tumours.

LDHA and brain tumour growth and survival Reports predominantly indicate that LDHA suppression inhibits tumour cell proliferation and survival [3, 26]. Aerobic glycolysis benefits cancer cells by avoiding generation of reactive oxygen species by oxidative phosphorylation, and the intermediates of the citric acid cycle (required for oxidative phosphorylation) are utilised to synthesise the lipids, fatty acids and nucleotides required for rapid cell proliferation [27].

Interestingly, recent studies have demonstrated that LDHA is inhibited in the Isocitrate dehydrogenase (IDH) subgroup of glioblastoma (GBM) which characteristically has a slower progression, greater survival rates and better prognosis than the other GBM subgroups [28]. Even brain tumour stem cell (BTSC) lines which once had IDH mutations but lost their mutant IDH allele had silenced LDHA. Analysis of data from The Cancer Genome 184

Atlas and REMBRANDT public databases, revealed that low expression of LDHA and high methylation of the LDHA promoter was found in IDHmt GBM patients and glioma patients whose tumours overexpressed LDHA had a median survival of 16 months whereas patients whose tumour under-expressed LDHA had a median survival of >50 months [28]. These studies suggest that the silencing of LDHA in GBMs with IDH mutations may be responsible in part for the characteristically slow progression of IDH mutant GBMs.

LDHA and brain tumour migration and metastasis Secondary brain tumours, derived from other cancers such as breast, lung and melanoma, are the most common type of adult brain tumour and the reported incidence is rising. LDHA expression correlates with metastasis and poor patient prognosis in many tumours [11, 29].

The most frequently reported mechanism by which LDHA modulates cell migration and invasion is through lactate production.

Lactate causes acidification of the microenvironment which promotes tumour cell invasion by inducing apoptosis of normal cells and pH-dependent activation of metalloproteinases (MMPs) and cathepsins which degrade the extracellular matrix and basement membranes [30, 31]. Seliger et al found that, in high grade glioma cell lines, the knockdown of LDHA resulted in a decrease in lactate

concentrations which caused a reduction of THBS-1 and TGF-β2 expression and reduced migration by approximately 40% compared to the control [32]. Furthermore, addition of lactate or synthetic THBS-1 rescued TGF-β2 expression and glioma migration [32]. In another study it was found that MMP-2, which is over-expressed in high-grade glioma, is also up-regulated

by LDHA through lactate induction of TGF-β2 [33]. It is probable that reducing lactate production through targeting LDHA would cause a reduction in metastasis and prolong patient survival.

LDHA and brain tumour evasion of the immune response Again, it is thought that lactate generation, promoted by LDHA, is the predominant cause of LDHA-mediated evasion of the immune response [34]. A study in GBMs revealed that LDHA induced the transcription and expression of natural killer group 2 member D (NKG2D) ligands on circulating monocytes and tumour infiltrating myeloid cells [35]. Chronic exposure to NKG2D ligands expressed by monocytes down-regulates the expression of NKG2D receptors on natural killer cells, preventing their ability to lyse NKG2D ligand-expressing tumour cells [36]. Previous studies in glioma have also shown that TGF-β can decrease NKG2D expression on NK cells in vitro [37]. As discussed previously, lactate production by Volume 10 Issue 6 • January/February 2016

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LDHA activates TGF-β in glioma [33]; therefore it is possible that LDHA also activates TGF-β to promote evasion of the immune response.

LDHA and the brain tumour microenvironment LDHA can influence the tumour microenvironment through generation of lactate which lowers pH. Primary brain tumours have been found to have a mean pH of 6.8 and as low as 5.9 compared to normal brain tissue which has a pH of 7.1 [38]. It has also been shown that an acidic pH induces glioma stem cell markers and promotes angiogenesis and malignancy, furthermore in vitro elevation of pH reversed these effects [39]. Angiogenesis is a hallmark of many tumours, including GBMs, and is stimulated by angiogenic factors including VEGF and IL-8. An acute acidic extracellular pH has been shown to promote up-regulation of VEGF in human glioma cells independently of hypoxia and furthermore hypoxia and acidic pH did not have a synergistic effect on VEGF transcription [40].

LDHA therapy development There are several LDHA inhibitors which have been used in vitro and in vivo studies in many types of cancer including oxamate [41], Galloflavin [42], Mn(II) complexes [43], quinoline 3-sulfonamides [44], azido and alkyne compounds [45] and N-hydroxyindole-based (NHI) inhibitors [46], all of which show promise but still require refinement in terms of specificity, potency and reducing toxic effects.

Unpublished studies by the Pilkington group have also shown that oxamate significantly reduces the proliferation and motility of MB cell lines. However in terms of brain tumours, Gossypol, a derivative of cotton seed oil, which inhibits LDHA and LDHC has shown the most promise [47]. Coyle et al found that gossypol treatment of mouse xenograft models decreased the mean weight of tumours by more than 50% and furthermore, the most sensitive glioma cell lines had higher LDHA expression levels [48]. Gossypol has been shown to be well tolerated in clinical trials and has also shown promise in recurrent malignant glioma trials [49, 50]. Two more clinical trials with gossypol and GBM have been completed (NCT00540722 and NCT00390403) but the results have not yet been published.

Summary Research has shown that LDHA and lactate are involved directly and indirectly in many aspects of tumour growth, migration, invasion and maintenance in a wide range of tumours (Figure 2) [3, 34]. Studies of LDHA and lactate in brain tumours have shown promise but the extent of these studies is severely lacking. Furthermore, targeting LDHA and tumour metabolism downstream of pyruvate synthesis is an attractive option as the effect on non-neoplastic cells should be minimal. Brain tumours are often more difficult to treat than other cancers as therapeutic drugs often have limited propensity to cross the protective blood-brain barrier (BBB). Although current available LDHA inhibitors are not approved for clinical use, to our knowledge, no groups have tested whether any potential LDHA inhibitors are even able to cross the BBB. This article is a brief summary of the function of LDHA and brain tumours which has been reviewed more extensively by Valvona et al [3].

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16. Lu R, Jiang M, Chen Z, et al. Lactate dehydrogenase 5 expression in NonHodgkin lymphoma is associated with the induced hypoxia regulated protein and poor prognosis. PLoS One 203;8:e74853.

17. Taylor MD, Northcott PA, Korshunov A, et al. Molecular subgroups of medulloblastoma: the current consensus. Acta Neuropathol 2012;123:465-72.

18. Cui J, Shi M, Xie D, et al. FOXM1 Promotes the Warburg Effect and Pancreatic Cancer Progression via Transactivation of LDHA Expression. Clin Cancer Res 2014 Apr. 19. Shi M, Cui J, Du J, et al. A Novel KLF4/LDHA Signaling Pathway Regulates Aerobic Glycolysis in and Progression of Pancreatic Cancer. Clin Cancer Res 2014;20:4370-80.

20. Priller M, Pöschl J, Abrão L, et al. Expression of FoxM1 is required for the proliferation of medulloblastoma cells and indicates worse survival of patients.

Clin Cancer Res 2011;17:6791-801.

21. Liu M, Dai B, Kang SH, et al. FoxM1B is overexpressed in human glioblastomas and critically regulates the tumorigenicity of glioma cells.

Cancer Res 2006;66:3593-602.

22. Nakahara Y, Northcott PA, Li M, et al. Genetic and epigenetic inactivation of Kruppel-like factor 4 in medulloblastoma. Neoplasia 2010;12:20-7.

23. Reuss DE, Piro RM, Jones DT, et al. Secretory meningiomas are defined by combined KLF4 K409Q and TRAF7 mutations. Acta Neuropathol 2013;125:351-8.

24. Ueba T, Takahashi JA, Fukumoto M, et al. Expression of fibroblast growth factor receptor-1 in human glioma and meningioma tissues. Neurosurgery 1994;34:221-5; discussion 225-6.

25. Fan J, Hitosugi T, Chung TW, et al. Tyrosine phosphorylation of lactate dehydrogenase A is important for NADH/NAD(+) redox homeostasis in cancer cells. Mol Cell Biol 2011;31:4938-50.

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26. Le A, Cooper CR, Gouw AM, et al. Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc Natl Acad Sci USA 2010;107:2037-42.

27. Vander Heiden MG, Cantley LC, and Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009;324;1029-33.

28. Chesnelong C, Chaumeil MM, Blough MD, et al. Lactate dehydrogenase A silencing in IDH mutant gliomas. Neuro Oncol 2014;16:686-95.

29. Brizel DM, Schroeder T, Scher RL, et al. Elevated tumor lactate concentrations predict for an increased risk of metastases in head-and-neck cancer. Int J Radiat Oncol Biol Phys 2001;51:349-53.

30. Kato Y, Lambert CA, Colige AC, et al. Acidic extracellular pH induces matrix metalloproteinase-9 expression in mouse metastatic melanoma cells through the phospholipase D-mitogen-activated protein kinase signaling. J Biol Chem 2005;280:10938-44.

31. Goetze K, Walenta S, Ksiazkiewicz M, et al. Lactate enhances motility of tumor cells and inhibits monocyte migration and cytokine release. Int J Oncol 2011;39:453-63.

32. Seliger C, Leukel P, Moeckel S, et al. Lactate-Modulated Induction of THBS-1 Activates Transforming Growth Factor (TGF)-beta2 and Migration of Glioma Cells In Vitro. PLoS One 2013;8: e78935.

33. Baumann F, Leukel P, Doerfelt A, et al. Lactate promotes glioma migration

by TGF-beta2-dependent regulation of matrix metalloproteinase-2. Neuro Oncol 2009;11:368-80.

34. Hirschhaeuser F, Sattler UG, Mueller-Klieser W. Lactate: a metabolic key player in cancer. Cancer Res 2011;71:6921-5.

35. Crane CA, Austgen K, Haberthur K, et al. Immune evasion mediated by tumor-derived lactate dehydrogenase induction of NKG2D ligands on myeloid cells in glioblastoma patients. Proc Natl Acad Sci USA 2014 Aug.

BioMedES Ltd

Producing the very best definitive versions of your biomedical reports and papers www.biomedes.co.uk Why not contact us at: BioMedES Ltd Leggat House, Keithhall, Inverurie, AB51 0LX, UK. T: +44-1467-6702809, F: +44-1467-629123, E: info@biomedes.co.uk

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36. Oppenheim DE, Roberts SJ, Clarke SL, et al. Sustained localized expression of ligand for the activating NKG2D receptor impairs natural cytotoxicity in vivo and reduces tumor immunosurveillance. Nat Immunol, vol. 6, pp. 928-37, Sep 2005.

37. Crane CA, Han SJ, Barry JJ, et al. TGF-beta downregulates the activating receptor NKG2D on NK cells and CD8+ T cells in glioma patients. Neuro Oncol 2010;12:7-13.

38. Vaupel P, Kallinowski F, and Okunieff P. Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumors: a review. Cancer Res 1989;49:6449-65.

39. Hjelmeland AB, Wu Q, Heddleston JM, et al. Acidic stress promotes a glioma stem cell phenotype. Cell Death Differ 2011;18:829-40.

40. Fukumura D, Xu L, Chen Y, et al. Hypoxia and acidosis independently up-regulate vascular endothelial growth factor transcription in brain tumors in vivo. Cancer Res 2001;61:6020-4.

41. Zhai X, Yang Y, Wan J, et al. Inhibition of LDH-A by oxamate induces G2/M arrest, apoptosis and increases radiosensitivity in nasopharyngeal carcinoma cells. Oncol Rep 2013;30:2983-91.

42. Farabegoli F, Vettraino M, Manerba M, et al. Galloflavin, a new lactate dehydrogenase inhibitor, induces the death of human breast cancer cells with different glycolytic attitude by affecting distinct signaling pathways. Eur J Pharm Sci 2012;47:729-38.

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• BioMedES reworks sound scientific papers, technical reports, and other (biomedical) documents, putting them into the most idiomatic English and passes the most stringent peer review and quality control assessments • It copy edits for a number of big biomedical publishing houses • Runs four journals in the life sciences

43. Xue JJ, Chen QY, Kong MY, et al. Synthesis, cytotoxicity for mimics of catalase: Inhibitors of lactate dehydrogenase and hypoxia inducible factor.

Eur J Med Chem 2014;80C:1-7.

• It provides the Secretariat for an international organisation for cell biology (www.ifcbiol.org) and an enterprise company

44. Billiard J, Dennison JB, Briand J, et al. Quinoline 3-sulfonamides inhibit lactate dehydrogenase A and reverse aerobic glycolysis in cancer cells. Cancer Metab 2013;1:19.

• It prepares and publishes e-books in biomedicine

45. Moorhouse AD, Spiteri C, Sharma P, et al. Targeting glycolysis: a fragment based approach towards bifunctional inhibitors of hLDH-5. Chem Commun (Camb) 2011;47:230-2.

• It designs logos for biomedical and many other organisations

46. Granchi C, Roy S, Giacomelli C, et al. Discovery of N-hydroxyindole-based inhibitors of human lactate dehydrogenase isoform A (LDH-A) as starvation agents against cancer cells. J Med Chem 2011;54:1599-612.

• It collates and prepares abstracts for scientific and other meetings

47. Lee CY, Moon YS, Yuan JH, et al. Enzyme inactivation and inhibition by gossypol. Mol Cell Biochem 1982;47:65-70.

48. Coyle T, Levante S, Shetler M, at al. In vitro and in vivo cytotoxicity of gossypol against central nervous system tumor cell lines. J Neurooncol 1994;19:25-35.

• The company is involved in arranging both national and international conferences • It also runs courses on scientific and medical writing, and on electronic publishing at home and abroad

49. Bushunow P, Reidenberg MM, Wasenko J, et al. Gossypol treatment of recurrent adult malignant gliomas. J Neurooncol 1999;43:79-86.

50. Stein RC, Joseph AE, Matlin SA, et al. A preliminary clinical study of gossypol in advanced human cancer. Cancer Chemother Pharmacol 1992;30:480-2.

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Mapping tumour tissue: quantitative maps of histological whole slide images Histological imaging of tumour tissue 1

Jakob Nikolas Kather,

Student, Institute of Pathology / Computer Assisted Clinical Medicine.

1

Cleo-Aron Weis, Physician Scientist, Institute of Pathology.

Corresponding Author: 1

Frank Gerrit Zöllner,

Associate Professor, Computer Assisted Clinical Medicine, Medical Faculty.

1

University Medical Centre Mannheim, University of Heidelberg, Mannheim, Germany.

Immunohistochemistry (IHC) is the standard method to assess tumour tissue on a micro-scopic scale.

IHC selectively highlights microscopic structures in the tissue and yields quantitative information that can be used to answer questions like: “How many immune cells are present in a given tumour?”, “How many tumour cells are actively proliferating?”, or “How many blood vessels are present in the tumour?”. These questions are addressed by histopathologists who visually observe regions of immunostained slides of tumour tissue and count structures of interest, for instance, cells or blood vessels. In the clinic, this quantitative information can be then used to estimate the prognosis of a patient. For example, the number of blood vessels in tumour tissue is a prognostic factor for colorectal cancer patients [1].

Pathologists combine the excellent human vision and pattern recognition skills of the brain with an extensive training in tissue observation.

Traditionally, pathologists use only a microscope to identify and assess structures of interest manually.

However, the limitations of manual procedures are evident; besides the possibility of human error, the dimensions of tissue slides in high magnification are huge and it is not feasible to view the whole slide nor manually visualise or count any objects of interest. Therefore, microscopic structures such as blood vessels are only quantified in a small fraction of the entire tumour image [2]. However, tumour tissue is highly heterogeneous and adjacent tumour tissue areas may have very different properties [3].

This reflects a problem in traditional histopathology: if we only quantify objects in a small part of the whole image, we do not know how much the distribution of these objects varies in the rest of the image.

Quantitative approaches in digital pathology

Constantino Carlos Reyes-Aldasoro, Lecturer in Biomedical Image Analysis, SMCSE, City University London, London, UK. E: Constantino.Reyes-Aldasoro.1@ city.ac.uk

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Digital pathology offers a solution to this problem.

In principle, it is possible to use computer-based image analysis to automatically count objects in huge images. Microscopic tissue slides can be digitally scanned in high magnification to create digital whole slide images (WSI). Then, we can use automatic image processing procedures to extract all structures of interest from the original image.

The digitisation of histological slides and the data handling is a complex task that requires a cascade of several steps [4-6]. Several commercial tools are

available that can be used to deal with and process WSI. Also, as part of the “open microscopy” project (www.openmicroscopy.org), various tools to handle WSI have been developed: OMERO, a software application capable of handling large WSI and BioFormats, a programming library that can be used by other applications such as ImageJ or Matlab to read and write WSI files.

Regardless of which tool is used to extract objects from WSI, the result is comparable: after an image processing procedure we know how many of these structures are present in a given image and where exactly these structures are located. The data on its own is not always useful, it needs to be evaluated by a trained human observer who can then extract clinically relevant information from this data. Consequently, an important question in digital pathology is the following: how can we efficiently present quantitative information from a WSI to a human observer?

Example: how to count blood vessels in tumour tissue In this work, we will give an example of how to analyse quantitative data derived from a WSI. As an example we will use the topic of blood vessel density in human tumours. Blood vessels play an important role in solid tumours as they supply the tumour cells with oxygen and nutrients. Blood vessels can be counted in immunostained images and their density is inversely correlated to patient survival in colorectal cancer and other cancer types [1]. Thus, the questions of how exactly blood vessels are distributed in tumour tissue might have relevant implications for the clinic.

We assume that our starting point is a tumour tissue stained by IHC so that blood vessels are of a specific colour. We can then scan this slide and feed the resulting WSI into a computer program that performs object recognition and records the exact position of each blood vessel within the tumour tissue [7,8]. Given the resolution and size of a WSI, it is relevant to ask how do we then make sense of this huge amount of data? The most straightforward approach would be to use only the total number of blood vessels and normalise them to the tissue area. The result is a single number, e.g. 100 blood vessels per mm2. This simple approach is useful to characterise the overall degree of angiogenesis in tumours [9]. However, by breaking down all measurements to a single number, we lose all information about the spatial distribution of blood vessels.

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Quantitative maps of tumour tissue Another approach to visualise the blood vessel distribution in tumour tissue is a map. In a map, each object of interest is displayed, for example, in a twodimensional coordinate system. However, typically we are not interested in individual objects, but in distribution parameters on a higher scale, for instance, local density of objects. Thus, instead of displaying every single blood vessel in a tumour tissue section, we can instead derive a quantitative map of the local blood vessel density. In general, these maps represent the spatial description of a feature of interest in a given tumour. These type of quantitative maps enable us to evaluate objects in large images and show the result to a human observer. In Figure 1, the processing cascade from tumour tissue to data analysis is shown.

In our case, we are interested in a quantitative density map that displays the local density of blood vessels (as represented by a numeric value) at each location of the original WSI. Figure 2 shows an example of a WSI stained for blood vessels with CD34 and its corresponding blood vessel density as calculated automatically with the algorithm described in [7]. In the quantitative map of blood vessel density (figure 2D), each point in the image is assigned a colour that corresponds to the local blood vessel density at this particular location. Another interesting feature of quantitative maps of tumour tissue: The data represented in the map can be analysed by means of spatial statistics. For example, we can objectively identify statistically significant areas of high object density, i.e. hotspot areas (Figure 2D, Figure 1) [7].

Figure 1: Processing pipeline to create and analyse a quantitative map of a histological whole slide image. A piece of tumour tissue is cut into slices, undergoes immunostaining and is digitized using a scanning microscope. Then, automatic image analysis produces a continu-ous map of features of interest, which can be analysed by means of spatial statistics.

Established applications of quantitative maps We have previously shown that quantitative maps of WSI are useful to assess blood vessel distribution [7]. Additionally, maps of tumour WSI have been successfully applied in a number of other studies. For example, they were shown to be useful to describe the density of immune cells in solid tumours [10]. In this case, the density of immune cells at the interface between tumour metastasis and healthy tissue was an excellent predictor of survival [11]. In breast cancer, specific spatial distribution patterns of immune cells were associated with different clinical parameters [12]. Another study showed that it is possible to assess many different antigens at once and, by image registration, compare the co-localisation of these antigens [13]. Alternatively, several antigens can be assessed simultaneously by using multiplex staining [14].

Even more information about spatial characteristics of histological slides can be acquired by a relatively novel technology called Matrix-Assisted Laser Desorption/Ionisation Imaging Mass spectrometry (MALDI IMS). This method has been used to measure the concentration of specific molecules in each location on a histological slide and produce a map of the distribution of each molecule of interest [15].

Ultimately, morphological analysis of WSI could be combined with MALDI IMS data and other “Omics” technologies [16].

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Figure 2: An example of a quantitative map: analysis of blood vessel hotspots in an image of a section through a colorectal carcinoma. A) Original whole slide image of a colorectal carcinoma, stained for the blood vessel marker CD34.

B) Enlarged detail showing blood vessels in brown. C-D) Result of automatic analysis: the region of interest has been used to create a continuous map of blood vessel density. Black = low blood vessel density, yellow = high blood vessel density. Five statistically significant hotspots have been detected (white arrow-heads).

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Future directions for quantitative maps in histology There are many interesting applications that could be addressed by quantitative maps in the future. For instance, it has been shown that proliferating tumour cells in hepatocellular carcinoma are predominantly located at the tumour margins as compared to the tumour centre [17]. However, to our knowledge, this finding has never been validated in WSI of different types of cancer. A quantitative map of proliferating tumour cells could be useful to model the distribution of proliferating tumour cells within tumours more accurately.

Another example is the distribution of particular genetic alterations in a tumour. For example, breast cancer and gastric cancer often contain HER2 overexpressing cells. However, cells in adjacent tissue areas in these tumours sometimes show different degrees of HER2 overexpression. How exactly these cell populations are distributed in a tumour has never been investigated in whole slide images. This question could be addressed by using a quantitative map of HER2 positive cells within the tumour, which could potentially lead to clinically relevant conclusions.

Summary Continuous maps are a useful approach to visualise object distributions and calculate spatial statistics based on histological whole slide images. These maps are a very intuitive way of displaying spatial data and human observers can easily extract information from these maps. Thus, by using quantitative maps, the unsurpassed pattern recognition capacities of human observers are efficiently combined with the quantitative power of automatic computer based analysis.

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References 1. Des Guetz G, et al. “Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature”, Br J Cancer, 2006;94(12):1823–32.

2. Vermeulen PB, et al. Second international consensus on the methodology and criteria of evaluation of angiogenesis quantification in solid human tumours. Eur J Cancer 2002;38(12):1564–79.

3. Gerlinger M, et al. Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N Engl J Med 2012;366(10):883–92.

4. Ghaznavi F, et al. Digital imaging in pathology: whole-slide imaging and beyond. Annu Rev Pathol 2013;8:331-59.

5. Kothari S, et al. Pathology imaging informatics for quantitative analysis of whole-slide images. J Am Med Inform Assoc 2013;20(6):1099-108.

6. Pantanowitz L, et al. Review of the current state of whole slide imaging in pathology. J Pathol Inform 2011; 2, 36.

7. Kather JN, et al. Continuous representation of tumor microvessel density and detection of angiogenic hotspots in histological whole-slide images. Oncotarget 2015;6(22): 19163–76.

8. Reyes-Aldasoro CC, et al. CAIMAN: an online algorithm repository for Cancer Image Analysis. Comput Meth Prog Bio 2011;103(2): 97–103.

9. Eberhard A, et al. Heterogeneity of Angiogenesis and Blood Vessel Maturation in Human Tumors: Implications for Antiangiogenic Tumor Therapies. Cancer Res 2000;60(5),1388– 93.

10. Halama N, et al. Quantification of prognostic immune cell markers in colorectal cancer using whole slide imaging tumor maps. Anal Quant Cytol Histol 2010; 32(6):333–40.

11. Halama N, et al. Localization and density of immune cells in the invasive margin of human colorectal cancer liver metastases are prognostic for response to chemotherapy. Cancer Res 2011;71(17):5670–7.

12. Nawaz S, et al. Beyond immune density: critical role of spatial heterogeneity in estrogen receptor-negative breast cancer. Mod Pathol, 2015;28,766-77.

13. Moles Lopez X, et al. Registration of whole immunohistochemical slide images: An efficient way to characterize biomarker colocalization. J Am Med Informatics Assoc 2015;22(1),86-99.

14. Isse K, et al. Digital transplantation pathology: combining whole slide imaging, multiplex staining and automated image analysis. Am J Transplant 2012;12(1):27-37.

15. Powers TW, et al. MALDI imaging mass spectrometry profiling of N-glycans in formalinfixed paraffin embedded clinical tissue blocks and tissue microarrays. PLoS One 2014;9(9), e106255.

16. Heindl A, et al. Mapping spatial heterogeneity in the tumor microenvironment: a new era for digital pathology. Lab Invest 2015;95(4):377-84.

17. Waclaw B, et al. A spatial model predicts that dispersal and cell turnover limit intratumour heterogeneity. Nature 2015;525(7568):261-4.

Volume 10 Issue 6 • January/February 2016

BOOK REVIEWS

Radiotherapy in Prostate Cancer – Innovative Techniques and Current Controversies Editors: Geinitz, Hans, Roach III, Mack, van As, Nicholas. ISBN: 978-3-642-37099-1. Published by: Springer. Price: €124.79.

P

rostate cancer is the most common cause of cancer in men. A significant proportion of these patients receive radiotherapy, which has evolved rapidly. As a consequence, the outcomes and toxicity profiles have improved. Radiotherapy in prostate cancer is a comprehensive review of the innovative techniques with an exceptional overview of the current controversies in management.

The chapters in the book have been organised into clinically relevant eight parts which give us an overview of the non-surgical management of localised/locally advanced prostate cancer.

The first two parts are devoted to the treatment planning process and also throw light on the innovations in imaging. Various clinically relevant outcome measures are also examined.

The third part focuses on newer treatment modalities like IMRT & IGRT and also discusses the impact of dose escalation on the treatment outcomes and toxicity.

The fourth part is a particularly interesting read as it covers the management of locally advanced disease and the surrounding controversies. The evidence behind prophylactic whole pelvic Radiotherapy is particularly dealt with excellently arguing the case

for and against.

The radiobiological aspects of hypofractionation and techniques of extreme hypofractionation like stereotactic body radiotherapy (SBRT) have also been adequately covered.

LDR seed and HDR brachytherapy are discussed in the brachytherapy section. A novel concept of focal therapy with radiation is introduced.

The final few chapters provide insight into the evidence for adjuvant and salvage radiotherapy.

Upcoming cutting edge technologies like Proton therapy and Heavy ion therapy are also covered.

This book is well written with good number of illustrations, high quality pictures, informative summary tables, succinct conclusion at the end of the chapters and is appropriately referenced. There are very few spelling mistakes which may be ignored. In summary, this is an excellent evidence based material for an update about modern radiotherapy for prostate cancer. It is a welcome addition to any medical library.

Harsih Reddy, Consultant Clinical Oncologist at Southampton University Hospitals NHS Foundation Trust.

A step-by-step approach Surgery for Ovarian Cancer, Third Edition Robert E. Bristow, Beth Y. Karlan, Dennis S. Chi

Updated and expanded, the third edition of Surgery for Ovarian Cancer focuses on essential techniques for the effective management of ovarian cancer. It reflects the most contemporary science and surgical applications for the management of patients with ovarian cancer and related peritoneal surface malignancies.

December 2015 | 437 Pages 317 Color images | 9781482236927

20% discount on all oncology books

Visit: www.bit.ly/ClinicalOncologyCRC to automatically receive your discount

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Bridging the gap in Breast Cancer surgical planning and aesthetic outcome prediction: The European PICTURE Trial Mo R Keshtgar

B

LUMC, Leiden, The Netherlands On behalf of the PICTURE Consortium

reast cancer is the most common cancer in women. According to recent worldwide data, this disease accounted for 23% (1.38 million) of the total new cancer cases [1]. The incidence is rising in most countries [2].

Since breast cancer is an increasingly treatable disease and 10-year survival now exceeds 80%, many women will live a long time with the aesthetic consequences of their treatment.

Majority of women with early breast cancer are offered breast conserving surgery as an alternative to the classic mastectomy. This conservative approach, combined with radiotherapy, has made local control of the disease possible, with survival rates similar to those obtained with mastectomy, but with better aesthetic result [3,4].

The increase in breast conserving surgery imposes greater expectations from patients on the quality of their aesthetic surgical outcome.

Oncoplastic surgery has developed to address this issue.

Whilst the oncological outcome of breast conservation procedures can easily be assessed objectively, the aesthetic outcome does not yet have an agreed evaluation standard. The assessment of the aesthetic result, as a means to evaluate one of the aspects of treatment quality, has become essential to any institution performing breast cancer treatment [5].

Corresponding author: m.keshtgar@ucl.ac.uk

Clinical context and tools for surgical planning

Royal Free London Foundation Trust, London, UK.

Maria J Cardoso Champalimaud Foundation, Portugal.

Gerrit-Jan Liefers

The aesthetic results and patients’ Quality of Life (QoL) have become fundamental objectives in breast conserving surgery. There are a number of factors affecting the aesthetic outcome after breast conserving surgery. These can broadly be divided into patient, tumour, and treatment-related factors.

Current standard of care in surgical planning of breast surgery is the preoperative localisation of

the tumour either based on palpation, ultrasound or on x-ray mammography. Before the operation, the surgical plan is drawn manually onto the skin of the patient, during the operation the surgeon is guided by these drawings.

There is a lack of universally accepted tools for surgical planning in helping patients to choose between available operative techniques.

Moreover it is not easy to demonstrate to patients the aesthetic image of the treatment result. The patient’s own perceptions about the results of her surgery may not concur with the perception of a third party [4]. Published results show that about 30% of patients are dissatisfied with their aesthetic outcome [6]. It is of paramount importance that patients should have realistic expectations from the outcome of surgery and for that they should have access to a tool that could demonstrate how the aesthetic outcome would be in their own situation using different techniques.

There is a need for development of better tools for surgical planning in breast conserving surgery, and tailored to the individual patient.

The combination of 3D photography and routinely acquired radiological images (i.e. mammography, ultrasound and MRI, when available), together with biomechanical modelling and MR elastography, will go a long way to addressing these requirements. Such tools can be used for surgical planning, and to objectively predict and subsequently evaluate the individual patients’ aesthetic outcome after treatment which can empower patients in the decision making process.

The PICTURE Project The PICTURE project funded by the European Union FP7 programme aims to bridge the current gap and address the unmet needs in this area.

This is a collaborative project between 5 Partners

Figure 1: Processing chain of the PICTURE demonstrator.

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in 7 Institutions within Europe.

The main aim of the project is to build a demonstrator system for planning and optimising breast conserving surgery.

The primary objective of the PICTURE project is thus the clinical demonstration and validation by building a software for planning and optimising breast-conserving surgery. The demonstrator will be used for three clinical tasks: 1. To predict suitability of patients for breast conserving surgery and the likely aesthetic outcome of the procedure, 2. To communicate the information on the type of breast surgery available and empower patients to take an active role in the shared decision making process, 3. To objectively evaluate the patient’s aesthetic result after treatment in comparison with the predicted outcome.

This is achieved by integrating patientspecific imaging data, photographs, tissue parameters, and patient-specific treatment plans with anatomical models, statistical shape models, biomechanical models, models of treatment response, and models of aesthetic outcome for use in patient care, basic research, and shared decision making.

How is this achieved?

It is achieved by a creation of a coherent representation of the patient’s health status related to breast surgery, the Digital Breast Surgery Patient. In the breast cancer care pathway, a patient undergoes many different types of examinations before a diagnosis is established and before a treatment decision is taken.

These examinations range from manually palpating the breast to modern medical imaging. Each of these examinations produces relevant data on the health status of the patient. In addition, other data of the patient must be included, e.g. non-image data like age, body mass index, staging etc. How to process these data and to combine it in a coherent way with physiological models is an unsolved question and is tackled within the PICTURE project. The Digital Breast Surgery Patient will be the point of integration for • all the patient specific data (imaging as well as non-imaging), • patient specific data, but derived from (imaging) data, • population based statistical data, • biophysical tissue models.

(Figure 1) In the scope of PICTURE, we aim to make the outcome of breast-conserving surgery Volume 10 Issue 6 • January/February 2016

more predictive. In the pre-operative workflow, surgical planning is an essential step. Here, the surgeon uses the available information to define the details of the planned operation, e.g. tumour position, resection margins, surgical technique, etc.

PICTURE will therefore develop tools for the interaction with the Digital Breast Surgery Patient during surgical planning, which allow visualisation of the procedure as well as the predicted outcome.

Special emphasis will be given to a visualisation of the planning result not only for the eyes of the surgeon, but also for use during the surgeon/patient interaction in a shared-decision-making setting (Figure 2).

Development of criteria to assess the result of a breast-conserving surgery from the perspective of cosmesis is another important aim of the project. PICTURE will investigate these criteria with the help of a consensus evaluation on patient data. Once objective criteria are known, the corresponding features are derived from the information in the Digital Breast Surgery Patient.

PICTURE will hence develop a module to (semi-) automatically determine these features from patient images or surface scans. In the surgical planning process, this module will be used on the result of a biophysical simulation to quantify the aesthetic outcome of a given surgical plan.

After almost three years of dedicated work by collaborating centres; we are pleased announce the launch of our demonstrator at the Royal Free London Hospitals NHS Foundation Trust.

Figure 2: Fusion of upright 3D photography and prone MRI enables a realistic surface rendering of the surgical simulation to be presented to the patient, using a patient specific biomechanical model of the breast anatomy.

References 1. Bray JA, Center F, Ferlay MM, et al. Global cancer statistics CA Cancer. J.Clin 2011;61:69-90.

2. Ferlay J, Steliarova-Foucher E, Lortet-Tieulent J, et al. Cancer incidence and mortality patterns in Europe: estimates for 40 countries in 2012. Eur.J.Cancer 2013;49;1374-403.

3. Veronesi U, Cascinelli N, Mariani L, et al. Twentyyear follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002;347;122732.

4. Christie DRH, O’Brien MY, Christie JA, et al. A comparison of methods of cosmetic assessment in breast conservation treatment. The Breast 1996;5;358-67.

5. Cardoso MJ, Cardoso JS, Vrieling C, et al.

Recommendations for the aesthetic evaluation of breast cancer conservative treatment. Breast Cancer Res Treat 2012;135;629-37.

6. Wang HT, Barone CM, Steigelman MB, et al.

Aesthetic outcomes in breast conservation therapy.

Aesthet.Surg.J 2008;28;165-70.

Acknowledgement: “The research leading to these results has received funding from the European Community’s Seventh Framework Programme under grant agreement no.

600948.”

We also acknowledge the PICTURE Trialists Group: CMIC University College London; Champalimaud Foundation, INESC Porto; King‘s College London; Leiden University Medical Center, Leiden; Philips Research, Hamburg; Royal Free London NHS Foundation Trust. http://www.vph-picture.eu.

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Review of transoral robotic surgery

Giri Wijayasingam, FRCSEd(ORL-HNS), Head and Neck fellow, Derby Teaching Hospitals NHS Foundation Trust, Derby, UK.

Mr M De, FRCS(ORL-HNS), Consultant, Derby Teaching Hospitals NHS Foundation Trust, Derby, UK. Correspondence to: wijayasingam@me.com

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ransoral robotic surgery (TORS) is an acceptable first treatment for early (T1 and T2) head and neck squamous cell carcinoma (HNSCC) because it has advantages over transoral laser (TLM) and open surgery. These include short hospital stay, short mean oral intake time less morbidity, avoidance of major resection (e.g. lip and mandibular split, tracheostomy and associated morbidty).

TORS can be an option for HPV-positive oropharyngeal squamous cell carcinoma in healthy younger individuals where the long-term effects of chemo-radiotherapy are avoidable.

TORS as a surgical technique has several advantages over conventional open surgery or TLM, such as low morbidity, excellent 3D HD visualisation, multi-planar view and better surgical margin control [1]. It can give better access to oropharyngeal, hypopharyngeal and supraglottic tumours compared to TLM, and appears to have less morbidity than primary chemo-radiotherapy in the management of HNSCC. The efficacy of TORS has been confirmed for both oncologic as well as postoperative functional results [2].

Hospital stay with TORS is shorter and patients start swallowing earlier, with a shorter duration of the use of nasogastric (NG) tube.

Patient experience less pain post operative pain and needs fewer tracheostomies compared to the conventional open surgery [3]. Hence it is cost effective in the long-term. Lower frequency of pharyngo cutaneous fistula compared to open surgery in case of concurrent neck dissection [4]. TORS has changed the workup for

unknown primary tumour; with mucosectiomies, many primaries have been identified in the tongue base and are treated accordingly [5].

Prospective studies have shown an improvement in function and quality of life outcomes in patients with TORS with adjuvant radiation or chemoradiation (CRT) treatment versus standard chemoradiation therapy [6].

The percutaneous endoscopic gastrostomy (PEG) dependency rate is 30-50% after 1 year in patients after primary CRT for pharyngeal and laryngeal malignancy. Other long term complications of high-dose radiotherapy to head and neck are loss of laryngeal sensation, tooth decay, xerostomia, carotid stenosis, osteo radio necrosis of the mandible, and radiationinduced sarcomas [1]. A large retrospective analysis of 16,188 patients in the National Cancer Data Base shows that survival was highest in patients who underwent surgery plus radiation compared to either radiation alone or combined chemoradiation in patients with advanced-stage disease [6].

TORS is en bloc resection compared to TLM, making pathological analysis easier, including definition of margins that allows completeness of resection. This will reduce rebiopsies and false positive margins encountered with TLM surgery [7].

TORS saved $1366 in cost and an increase of 0.25 quality-adjusted life years (QALYs) per case in comparison to (chemo) radiotherapy [8], with Richmond et al [9] reporting large savings following TORS procedure. Patients had a lower rate of gastrostomy (0 vs. 19%) and tracheotomy tube placements (0 vs. 36%) compared to patients undergoing non-TORS procedures. TORS significantly decreased length of hospitalization (mean reduction 1.5 days) and hospital-related costs (mean $4,285) [9].

The ideal candidates for TORS are patients with: no general contraindication for surgery, primary tumours that are readily resectable, no radiological sign of nodal extra capsular spread, and clear surgical margins. Surgery probably eliminates the need for adjuvant chemoradiotherapy. It is important to consider the patient’s condition regarding mouth opening, dentition, neck length and jaw size [1].

Lorincz et al [10] reported on a series of 35 patients with T1 and T2 oropharyngeal squamous cell carcinoma undergoing TORS resection.

Clear resection margins were achieved in 33 of the 35 patients, with 5 patients having elective tracheostomy. All patients had a single dose Volume 10 Issue 6 • January/February 2016

HEAD AND NECK CANCER

of 250mg methyl prednisolone. After the procedure, all had NG tubes and were kept intubated overnight in the intensive care unit to keep their blood pressure low to prevent post-operative hemorrhage.

Adjuvant treatment was unnecessary in 13 patients [10].

TORS is increasingly used in surgery for laryngeal and hypopharyngeal cancer.

Ablative procedures described in these anatomical sites include supraglottic laryngectomy, partial laryngectomy, glottic cordotomy and partial pharyngectomy.

TORS supraglottic laryngectomy, are promising compared to other methods of treatment, being most commonly performed among these procedures and having initial good functional and oncologic outcomes (6). Virgilio et al [11] reported that in 10 patients with T1 and T2 hypopharyngeal, swallowing returned in 8.2 days and patients were decannulated after 6.1 days [11].

Weinstein et al [12] followed the outcome of 47 patients with T3 and T4 oropharyngeal cancer for a mean of 26 months. All surgical defects healed with secondary intention, and only one patient had positive margin. Of the 41 patients evaluated, 40 were able to swallow and take adequate nutrition.

Overall survival for 1 and 2 years was 95.7 and 81.8%, respectively. Villanueva et al [13] reported all 10 of their patients with oropharyngeal minor salivary gland tumours had negative margins after resection using TORS. Mehta et al [5] found that of 10 patients with unknown primary after pan-endoscopy and bilateral tonsillectomy who underwent TORS tongue base mucosectomy, 9 were positive for squamous cell carcinoma.

Durmus et al [14] identified the tumours and completely re-moved then with TORS 17 out of 22 patients with unknown primaries. Tumours were found in the tonsils (59.1%) and tongue base (18.1%).

O’Malley et al [15] showed the technical feasibility of accessing and performing tongue base resections without requiring a transcervical or transmandibular approach.

The exceptional high magnification and 3-D optics allowed careful en bloc resection, with identification of nerves and vessels. In a series of 44 patients who underwent TORS for parapharyngeal space tumours, Chan et al [16] found 29 patients had pleomorphic adenoma and 9 capsular breach including tumour fragmentation; all were pleomorphic adenoma. Their mean length of stay was 3 days and the mean Volume 10 Issue 6 • January/February 2016

time to oral intake was 1 day.

Despite its functional and oncologic efficacy, TORS is not without some serious complications. Life-threatening post-operative hemorrhage and airway obstruction leading to tracheostomy can occur. There was no significant difference in the overall post-operative hemorrhage rates in the prophylactically ligated (external carotid artery or its branches) versus non-ligated groups. There were 2 deaths reported in a major centre following TORS due to aspiration of blood into the lower airways. Post-mortem studies and multiple case reports showed anatomic variations contributing to the pharyngeal vascular supply from the internal carotid artery through an aberrant branching pattern of the ascending pharyngeal artery [2].

In one series of 35 patients with T1 and T2 oropharyngeal SCC, 2 patients had post-operative bleeding on day 1 and another on day 6. In both the bleeding was identified in the primary re-section site and controlled with bipolar diathermy [11].

Chia SH et al [17] investigated 45 TORS trained surgeons in America who had treated 2015 patients; 6% of TORS procedures required tracheotomy or reconstruction. Of the patients who required readmission, bleeding (n=62, 3.1%) was the most common cause, followed by dehydration (n=26, 1.3%). Other complications of surgery included tooth injury (n=29, 1.4%), PEG dependency 6 months (n=21, 1.0%), temporary hypoglossal nerve injury (n=18, 0.9%), and lingual nerve injury (n=11, 0.6%). Six deaths (0.3%) occurred within 30 days of TORS, all due to post-operative hemorrhage. The complication rate decreased significantly with higher surgeon case volume (>50 cases).

Summary Transoral Rototic Surgery is a relatively new technique in United Kingdom. It is a valuable addition to currently available techniques in head and neck surgery.

Advantages of TORS are real time high definition 3 dimension vision and enhanced access to oropharynx, and supra glottis, and endowrist instrument which can move on many planes enables precise removal of tumour tissue, with preservation of normal tissue.

References 1. Balazs B, Lorincz, MD, Nathan Jowett MD, et al.

Decision management in transoral robotic surgery: Indi-cations, individual patient selection, and role in the multidisciplinary treatment for head and neck cancer from a European perspective. Head & Neck 2015.

2. Mandal R, Duvvui U, Ferris RL, et al. Analysis of post-transoral robotic-assisted surgery haemorrhage, frequency, outcomes, and prevention. Head & Neck Accepted in April 2015.

3. Hammoudi K, Pinlong E, Kim S, et al. Transoral robotic surgery versus conventional surgery in the treat-ment for squamous cell carcinoma of the upper aerodigestive tract. Head & Neck. 2015; September:1304-1309.

4. Kucur C, Durrmus K, Gun R, et al. Safety and efficacy of concurrent neck dissection and transoral roboric surgery. Head & Neck 2015; January:1-5.

5. Mehta V, Johnson P, Tassler A, et al. New paradigm for the diagnosis and management of unknown pri-mary tumors of the head and neck: A role for transoral robotic surgery. Laryngoscope 2013; Jan;123(1):146-51.

6. Genden EM, O’Malley, Jr BW, Weinstein GS, et al.

Transoral Robotic Surgery: Role in the management of upper aerodigestive tract tumours. Head & Neck.

2012; June :886-92.

7. Hamzany Y, Bransu D, Shpitzer T, et al. Assessment of Margins in Transoral Laser and Robotic Surgery.

Rambam Maimoinides Med J 2014; Apr;5(2) e0016.

8. de Almeida JR, Moskowitz AJ, Miles B, et al.

Cost-effectiveness of transoral robotic surgery versus (chemo) radiotherapy for early T classification oropharyngeal carcinoma: A cost-utility analysis. Head & Neck 2015; January: 1-11.

9. Richmond JD, Quon H and Gourin CG. Effect of transoral robotic surgery on short-term outcomes and cost of care after oropharyngeal cancer surgery.

Laryngoscope 2014;124:165–71.

10. Lorincz BB, Mockelmann N, Busch CJ et al.

Functional outcomes, feasibility, and safety of resection of transoral robotic surgery: Single-institution series of 35 consecutive cases of transoral robotic surgery for oropharyngeal squamous cell carcinoma. Head & Neck. 2014.

11. Virgilio AD, Kim SH. A novel technique for treatment of hypopharyngeal cancer. European Archives of Oto-Rhino-Laryngology. Conference: 8th Congress of the European Laryngological Society Vienna Austria. 2011; May :268 (5):780.

[Journal: Conference Abstract] 12. Weinstein GS, O’Malley BW, Jr., Cohen MA, et al.

Transoral robotic surgery (TORS) for advanced oropharyngeal carcinoma. Arch Otolaryngol Head and Neck Surg. 2010;136:1079-85.

13. Villanueva NL, de Almelda JR, Sikora AG, et al.

Transoral robotic surgery for the management of oropharyngeal minor salivary gland tumours. Head & Neck 2014; January:28-33.

14. Durmus K, Rangarajan SV, Old MO et al. Transoral robotic approach to carcinoma of unknown primary.

Head & Neck 2014;June:848-52.

15. O’Malley BW, Jr., Weinstein GS, Snyder W, et al.

Transoral Robotic Surgery (TORS) for Base of Tongue Neoplasms. Laryngoscope 2006;116:1465-72.

16. Chan JYK, Tsang RK, Elsele DW et al. Transoral robotic surgery of the parapharyngeal space; A case series and systematic review. Head & Neck 2015; Feb;37(2):293-8.

17. Chia SH, Gross ND, Richmon JD. Experience and complications with Transoral Robotic Surgery (TORS).

Otolaryngology Head & Neck Surgery 2013; Dec;149(6):885-92.

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JOURNAL REVIEWS

New England Journal of Medicine Nivolumab versus Docetaxel in Advanced Squamous-Cell Non–Small-Cell Lung Cancer Julie Brahmer, Karen L Reckamp, Paul Baas and Lucio Crinò New England Journal of Medicine. 2015;May 31,DOI: 10.1056/ NEJMoa1504627

Background: For patients with advanced squamouscell non–small-cell lung cancer (NSCLC) with progression during or after first-line chemotherapy, there are limited treatment options. This randomised, open-label, international phase 3 study evaluated the efficacy and safety of nivolumab, a human IgG4 programmed death 1 (PD-1) immune-checkpoint inhibitory antibody, compared with docetaxel.

Methods: We randomly assigned 272 patients to receive nivolumab at 3mg per kg body weight every two weeks, or docetaxel at 75mg per square meter of body-surface area every three weeks. The primary end-point was overall survival (OS).

Results: The median OS was 9.2 months (95% confidence interval [CI], 7.3 to 13.3) with nivolumab vs 6.0 months with docetaxel (95% CI, 5.1 to 7.3). The risk of death was 41% lower with nivolumab than docetaxel (hazard ratio, 0.59; 95% CI, 0.44 to 0.79; P<0.001). At one year, the OS was 42% (95% CI, 34 to 50) with nivolumab vs 24% with docetaxel (95% CI, 17 to 31). The response rate was 20% with nivolumab vs 9% with docetaxel (P=0.008).

The median progression-free survival was 3.5 months with nivolumab vs 2.8 months with docetaxel (hazard ratio for death or disease progression, 0.62; 95% CI, 0.47 to 0.81; P<0.001). The expression of the PD-1 ligand (PD-L1) was neither prognostic nor predictive of benefit. Treatmentrelated adverse events of grade 3 or 4 were reported in 7% of the patients in the nivolumab group compared with 55% the docetaxel group.

Conclusion: Among patients with advanced previously treated squamous-cell NSCLC, OS, response rate and progression-free survival were significantly better with nivolumab than with docetaxel, regardless of PD-L1 expression level. (Funded by Bristol-Myers Squibb; CheckMate 017).

Reviewer’s comments: We are at a cross-road on the management of non-small cell lung cancers due to developments in biological markers and targeted therapies. Encouraging results on the use of these agents with different mechanism of action and limited side effect concerns from currently on-going trials, even in previously treated relapsed non-small cell lung cancer, is encouraging. In 2015, targeted agents are valuable only for a selected group of lung cancer patients. Management with surgery, radiotherapy and conventional cytotoxic chemotherapy remains the backbone for majority.

Docetaxel continues to be a universally accepted standard second-line systemic therapy, with limited benefits and high incidence of toxicities and an average median survival of ~9 months. Therefore, we need to explore new

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therapies to improve the outcome of most of patients suffering from advanced/metastatic non-small cell lung cancer. Like CheckMate 057 for non-squamous cell lung cancer, these results from CheckMate 017 with the use of nivolumab in squamous cell cancer are promising and represent a major step in right direction. However, one must not lose sight of the fact that these results are interim analyses and a relatively short follow-up.

CheckMate 017 is a well-conceived and well-conducted trial with a large number of patients recruited, and has balanced characteristics within both arms. The results clearly show impressive and persistent improvement in PFS and OS with nivolumab. It is difficult to decide with any confidence whether nivolumab is more effective in squamous cell (HR 0.59, p=0.00025) that non-squamous cell cancer (HR 0.73, p=0.0015). Due to relatively smaller benefit with docetaxel, the overall incremental benefit seems to be greater with nivolumab in the squamous cell subtype. Therefore, for squamous cell histological subtype with which docetaxel does poorly, nivolumab could be the better option, except for the non-squamous subtype, and is now a new option. Further follow-up results could provide better estimates of its long-term survival gains.

The above results provide strong evidence that we could have a new class of drug for management of non-small cell lung cancer. Many other agents with different mechanism of actions are undergoing evaluation either on their own or in combination with docetaxel, for example anti-angiogenics, such as ramucirumab and nintedanib.

These agents may be effective against non-small cell lung cancer. The outlook looks promising for a new option.

Therefore, selection of the appropriate agent for the individual patient will be important. Its remains unclear whether anti PD-L1 or anti PD-1 will have the edge.

The cost, the level of PD-L1 expression and toxicity may influence its wider use. The MHRA has already given approval to nivolumab in early access to medicine (EAMS) for the treatment of locally advanced or metastatic squamous cell lung cancer after prior chemotherapy in UK. – SU

Journal of Clinical Oncology BEST: A Randomised Phase II Study of VEGF, RAF Kinase, and Mammalian Target of Rapamycin Combination Targeted Therapy with Bevacizumab, Sorafenib, and Temsirolimus in Advanced Renal Cell Carcinoma – A Trial of the ECOG-ACRIN Cancer Research Group (E2804) Flaherty KT, Manola JB, Pins M et al. Journal of Clinical Oncology. 2015; Jul 20;33(21):2384-91.

Purpose: From evidence that resistance to vascular endothelial growth factor (VEGF) receptor inhibition is caused by hypoxia-driven residual VEGF and other Volume 10 Issue 6 • January/February 2016

JOURNAL REVIEWS

proangiogenic factors, combinations of agents from these classes might improve treatment outcomes relative to VEGF pathway blockade with single-agents.

Patients and Methods: A total of 361 patients with metastatic clear cell renal cell carcinoma were randomly assigned equally to arm A (bevacizumab monotherapy 10mg/kg intravenously [IV] every two weeks), B (bevacizumab 10mg/kg IV every two weeks and temsirolimus 25mg IV every week), C (bevacizumab 5mg/kg IV every two weeks and sorafenib 200mg orally twice daily on days 1 to 5, 8 to 12, 15 to 19, and 22 to 26), or D (sorafenib 200mg twice daily and temsirolimus 25mg IV weekly). Progression-free survival was the primary end-point.

Results: Among 331 eligible treated patients, median PFS was 7.5 months for bevacizumab alone (90% CI, 5.8 to 10.8 months), 7.6 months for bevacizumab plus temsirolimus (90% CI, 6.7 to 9.2 months), 9.2 months for bevacizumab plus sorafenib (90% CI, 7.5 to 11.4 months), and 7.4 months for sorafenib plus temsirolimus (90% CI, 5.6 to 7.9 months). Hazard ratios from stratified Cox proportional hazards models were 1.01, 0.89, and 1.07 (with respective P values of 0.95, 0.49, and 0.68) for the three combinations, respectively, compared with bevacizumab alone. Adverse events did not differ significantly among treatment arms.

years with single-agent bevacizumab, although this is difficult to interpret without information on patients’ subsequent therapies. There was evidence of additional benefit in terms of objective response rate when either temsirolimus or sorafenib was added to bevacizumab.

However, the clinical importance of this remains uncertain in the absence of data on symptomatic improvement in these patients. Dose intensities of sorafenib and temsirolimus were suboptimal, particularly early in treatment, with doses lower than those administered in the pivotal Phase III singleagent trials. The amount of severe or life-threatening toxicity was 30-40% higher with combination therapy.

This study showed no synergy between these antiangiogenic and anti-mTOR therapies, or any delayed development of resistance with intolerably high rates of toxicity. The standard of care remains as sequential single-agent treatment, although we have to see whether the new generation of immunotherapeutic strategies, such as immune-checkpoint blockade (e.g. anti PD-1), would do better combined with antiangiogenic therapy. This combination is particularly intriguing in view of the immune-stimulating effects of sunitinib, such as reduction in circulating myeloidderived-suppressor-cells. – AR

Conclusion: The activity of sorafenib, temsirolimus, and bevacizumab administered in double combinations did not significantly improve median progression-free survival in comparison with bevacizumab monotherapy.

Reviewer’s opinion: The treatment of metastatic renal cell carcinoma (RCC), particularly the clear cell subtype, has been transformed in recent years by the introduction of both a monoclonal antibody and small-molecule tyrosine kinase inhibitors targeted against tumour angiogenesis (bevacizumab, sunitinib, sorafenib, pazopanib, axitinib). The rationale for anti-angiogenic treatment is that clear-cell RCC typically harbours deleterious somatic mutations in the VHL gene that lead to upregulation of HIF-1a and pro-angiogenic factors, such as VEGF and PDGFR. Drugs (e.g. temsirolimus and everolimus) interfering with the mTOR/MEK/PI3K/ERK pathway are also involved in advanced RCC. In clinical practice, these drugs are used sequentially as single-agent therapy (everolimus or axitinib typically as second-line therapy). This study explored the feasibility, safety and efficacy of combinations of anti-angiogenic and mTOR targeted therapies. The study population was restricted to clearcell histology, patients who had only received one prior line of immunotherapy (not anti-angiogenic therapy).

Approximately three-quarters of the patients were in the MSKCC good or intermediate risk categories, half of patients had extensive skeletal or hepatic metastases, and nearly one-third of patients had irresectable but non-metastatic disease. Combinational therapy had no benefit in terms of efficacy (% patients with stable disease at six months, median PFS and OS). Of some interest, the median overall survival approached 2.5

Volume 10 Issue 4 • September/October 2015

PANEL OF JOURNAL REVIEWERS Dr Qian An, PhD MD, Senior Research Fellow, Portsmouth University, UK. Mr Mriganka De, FRCS (ORL-HNS), Consultant ENT Head & Neck/Thyroid Surgeon, Derby Royal Hospital, UK. Ms Helen Evans, Senior Lecturer in Cancer Nursing, Institute of Nursing and Midwifery, University of Brighton, UK. Mr Tasadooq Hussain, BA(Edu.) (MD) MRCS a Clinical Research Fellow Breast Surgery at Castle Hill Hospital, Hull and Eat Yorkshire Hospitals NHS, UK. Richard Novell, MChir FRCS, Consultant Coloproctologist, The Royal Free Hospital, London, UK. Xinchao Pan, postdoctoral fellow, Department of Internal Medicine, Division of Nephrology in UT Southwestern Medical Center, Dallas, TX , USA. Dr Ankit Rao, ST5 in Medical Oncology, West Midlands Deanery, Birmignham, UK. Dr Sunil Upadhyay, Consultant Clinical Oncologist, Queen’s Centre for Oncology, Castle Hill Hospital, Hull, UK.

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EVENTS DIARY To have your event listed in the Oncology News diary, E: patricia@oncologynews.biz by February 4th 2016.

2016 January NEW National Acute Pain Study Day 13 January 2016; London, UK E: conferenceteam@rmh.nhs.uk T: +44 (0)20 7808 2921 W: www.royalmarsden.nhs.uk/ studydays NEW RSM Acute Oncology 2016 15 January 2016; London, UK E: oncology@rsm.ac.uk T: +44 207 290 2982 W: www.rsm.ac.uk/events/ocg02 NEW The CPC, Conférence Nationale des Plaies et Cicatrisations (The International Workshop on Wound Technology) 17-19 January 2016; Paris, France E: officemf@fr.oleane.com The Royal Marsden Head and Neck Cancer Study Day 18 January 2016; London, UK E: conferenceteam@rmh.nhs.uk T: +44 (0)20 7808 2921 W: www.royalmarsden.nhs.uk/ studydays

NEW HDR and Electronic Brachytherapy for Skin Cancer 21-22 January 2016; Manchester, UK E: education.events@christie.nhs.uk W: www.christie.nhs.uk/ school-of-oncology/ education-and-training.aspx

NEW Essential Oils Master Class Advanced formulation skills for cancer care: maximising therapeutic effectiveness in clinical aromatherapy 26 January 2016; London, UK E: conferenceteam@rmh.nhs.uk T: +44 (0)20 7808 2921 W: www.royalmarsden.nhs.uk/ studydays NEW Essential Oils in Cancer Care 2 Day Introductory Course 27-28 January 2016; London, UK E: conferenceteam@rmh.nhs.uk T: +44 (0)20 7808 2921 W: www.royalmarsden.nhs.uk/ studydays 14th Annual BTOG Conference 2016 27-29 January 2016; Dublin, Ireland BTOG T: +44 (0)116 250 2811 E: dawn.mckinley@uhl-tr.nhs.uk W: www.btog.org

NEW The British Skull Base Society Meeting 28-29 January 2016; Birmingham, UK Samantha Womack E: samantha.womack@ aesculap-academy.com or T: +44 (0)114 225 9035 NEW Essential Oils Rest, Recovery and Repair 29 January 2016; London, UK E: conferenceteam@rmh.nhs.uk T: +44 (0)20 7808 2921 W: www.royalmarsden.nhs.uk/ studydays

February

Malignant Melanoma and Beyond: An NEW introduction to targeted treatments Essential Oils Update Day and Cancer immunotherapy 25 January 2016; London, UK 2 February 2016; London, UK E: conferenceteam@rmh.nhs.uk E: conferenceteam@rmh.nhs.uk T: +44 (0)20 7808 2921 T: +44 (0)20 7808 2921 W: www.royalmarsden.nhs.uk/ W: www.royalmarsden.nhs.uk/ StratechAd_Oncology180x65 10/09/2014 13:27 Page 1 studydays studydays

The Royal Marsden Radiotherapy Study Day 8 February 2016; London, UK E: conferenceteam@rmh.nhs.uk T: +44 (0)20 7808 2921 W: www.royalmarsden.nhs.uk/ studydays Biological Basis of Cancer: Radiobiology and Statistics 8 –12 February 2016; Manchester, UK E: education.events@christie.nhs.uk W: www.christie.nhs.uk/ school-of-oncology/ education-and-training.aspx

NEW Foundations Oncology Skills for Nurses New to Working in Paediatric and Adolescent Cancer Care 9-10 February 2016; London, UK E: conferenceteam@rmh.nhs.uk T: +44 (0)20 7808 2921 W: www.royalmarsden.nhs.uk/ studydays NEW The Royal Marsden Imaging Group: Everything you ever wanted t0 know about Prostate and Bladder Cancer Imaging 20 February 2016; London, UK E: conferenceteam@rmh.nhs.uk T: +44 (0)20 7808 2921 W: www.royalmarsden.nhs.uk/ studydays NEW British Neurovascular Group Meeting 25-26 February 2016; Redworth, County Durham, UK Samantha Womack E: samantha.womack@ aesculap-academy.com T: +44 (0)114 225 9035

March

The 11th Palliative Care Congress 9-11 March 2016; Glasgow, UK T: +44 (0)1489 565475 E: sales@compleatconference.co.uk W: www.pccongress.org.uk

NEW The Changing Prospects for Cancer 11 March 2016; Manchester, UK E: education.events@christie.nhs.uk W: www.christie.nhs.uk/ school-of-oncology/ education-and-training.aspx Innovations in Cancer Research Study Day 14 March 2016; London, UK E: conferenceteam@rmh.nhs.uk T: +44 (0)20 7808 2921 W: www.royalmarsden.nhs.uk/ studydays

NEW Children and Young People’s Palliative Care Study Day 16 March 2016; London, UK E: conferenceteam@rmh.nhs.uk T: +44 (0)20 7808 2921 W: www.royalmarsden.nhs.uk/ studydays Molecular Pathology: Current Topics Symposium 17 March 2016; London, UK E: conferenceteam@rmh.nhs.uk T: +44 (0)20 7808 2921 W: www.royalmarsden.nhs.uk/ conferences 3rd ImmunoTherapy of Cancer Conference 21–23 March 2016; Munich, Germany E: marjorie@itoc-conference.eu W: www.itoc-conference.eu

April NEW

National Oncoplastic Breast Cancer Surgery Study Day 7 March 2016; London, UK E: conferenceteam@rmh.nhs.uk T: +44 (0)20 7808 2921 W: www.royalmarsden.nhs.uk/ studydays

Cytotoxic Medication Study Day for Nurses New to Cytotoxic Treatment 13 April 2016; London, UK E: conferenceteam@rmh.nhs.uk T: +44 (0)20 7808 2921 W: www.royalmarsden.nhs.uk/ studydays

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Volume 10 Issue 6 • January/February 2016

BRITISH ASSOCIATION OF HEAD & NECK ONCOLOGISTS www.bahno.org.uk

BAHNO Secretariat PO Box 85 Midhurst, West Sussex GU29 9WS

Tel: 01730 813700 Fax: 01730 812042 Email: secretariat@bahno.org.uk

BAHNO ANNUAL SCIENTFIC MEETING 2016 Joint Meeting with Allied Health Professionals Royal College of Physicians, London Friday 13th May 2016

‘The Management of Head and Neck Cancer; at what cost?’

08.00 - 08.45 08.45 - 08.50 08.50 – 09.00 09.00 – 09.30 09.30 - 10.40 10.40 - 11.00 11.00 - 11.05

11.05 - 11.50

12.00 - 12.45 12.45 - 13.30 13.30 - 14.00 13.30 – 15.15 14.00 - 15.15 15.15 - 15.45 15.45 - 17.00 17.00

Registration, Coffee, Trade Display, Poster display Welcome by the President HANA Update Nunn Lecture Free papers session one/Parallel AHP session one Coffee, Trade Display, Poster display Introduction to the Blair Hesketh Lecture President of the British Association of Head and Neck Oncologists Blair Hesketh Lecture Professor Joseph Helman, CJ Lyons Endowed Professor of Oral and Maxillofacial Surgery, University of Michigan Case based panel discussion: Parallel AHP session two Lunch, Trade Display, Poster display AGM Parallel AHP session three Free papers – Session Two Tea, Trade Display, Poster display Debate Title:- ‘This house believes that the NHS can afford transoral robotic surgery’ Closing remarks by the President of BAHNO

11-13 December 2016

RAI Amsterdam, The Netherlands

th

European Multidisciplinary Colorectal Cancer Congress

PICK UP YOUR COPY OF ONCOLOGY NEWS AT: BTOG in Dublin, January 2016 BAHNO in London, May 2016 BNOS in Leeds, June 2016 NCRI in Liverpool, November 2016 Contact Patricia for further information: T: +44 (0)288 289 7023 Patricia@oncologynews.biz www.oncologynews.biz

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NEWS UPDATE Latest developments on products and services from the industry. To have your news included contact Patricia McDonnell at Oncology News on T/F: +44 (0)288 289 7023, E: patricia@oncologynews.biz

Technology boost for cervical screening in Wales DP Medical Systems Ltd has secured a deal with Cervical Screening Wales to provide its pioneering image capture system for gynaecological examinations – MediScan – to hospitals across the country.

Twenty-six MediScan systems have been purchased by Cervical Screening Wales (CSW) – the Public Health Wales body responsible for the cervical screening programme – and will be installed in 19 hospital sites.

The service will be using a part of the MediScan software to interface with CSW’s existing software for the capture of vital images during gynaecological examinations.

The still images will be captured in real-time

DP Medical System Ltd’s MediScan

and stored against the patient record for retrieval anywhere in the hospital.

The MediScan system uses a simple to operate user interface and an optional

UK’s National Health Service selects 20 Varian TrueBeam Systems for cancer treatments

NHS Supply Chain has placed an order for a further 20 TrueBeam™ machines from Varian Medical Systems as part of an ongoing program to replace older machines and institute modern radiotherapy and radiosurgery treatments for patients in the UK’s public hospitals. The order, placed in September, also includes ten PerfectPitch treatment couches and 50 licenses for Varian’s RapidArc® and Eclipse™ software systems.

“As the leading provider of radiotherapy equipment and software to the NHS, Varian is committed to ensuring patients have access to cutting edge technology while also recognizing that modern healthcare must be efficient, effective and affordable,” said Adele Lyons of Varian Medical Systems. “The TrueBeam technology will enable the NHS to meet all of these objectives. We share a goal with the NHS to help save many more lives each year.”

Jason Lavery, Trading Director of Capital Solutions, NHS Supply Chain said: ‘By working in partnership with the NHSBSA, the Department of Health and Varian Medical Systems, we are all able to provide a structure for the NHS that supports both the national direction for providing world class cancer treatment and achieving best value in managing capital equipment. With the increasing pressure on budgets it is vital that we work together to maximise benefit for the NHS.’ For further information contact: Neil Madle, Varian Medical Systems, T: +44 7786 526068, E: neil.madle@varian.com W: www.varian.com 200

question and answer-based approach to data entry. Its digital still images are seen as benchmark quality by leading clinicians and have been used for illustration in medical texts.

Owen Pemberton, Commercial Director at DP Medical Systems Ltd, said: “MediScan will provide clinicians working across the field of cervical screening throughout Wales with superior image capture technology, meaning a more efficient service for healthcare providers – and ultimately, patients.”

For further information visit: www.dpmedicalsys.com/medical/gynae/ mediscan/

Leeds Cancer Centre marks 1,000th patient treated with potent, targeted stereotactic radiation therapy

On October 30 at Leeds Cancer Centre, St. James’s University Hospital, a 70-year-old male became the center’s 1,000th patient treated with stereotactic body radiation therapy (SBRT), which delivers an extremely accurate, high dose of radiation to tumor targets.

“We are treating him on our Elekta Versa HD™ system, which enables us to use the Volumetric Modulated Arc Therapy [VMAT] technique in addition to the system’s High Dose Rate mode,” says Vivian Cosgrove PhD, head of radiotherapy physics at St. James’s. The combination of these two Versa HD innovations allows us to deliver the session’s radiation in just under two minutes.”

St. James’s has been steadily building its SBRT program since April 2009. With the installation of two Versa HD systems in 2013, all SBRT treatments have been delivered with the fast High Dose Rate method – about 400 patients. The hospital treats approximately 10 patients each week with SBRT and receives 15 to 25 new referrals per month.

“Shorter treatment times are good news for patients,” adds Dr. Cosgrove. “The longer it takes to deliver the dose, the greater the risk that the patient will move. Reducing the beam delivery from our original time of seven minutes for this particular case to now under two minutes means it is significantly less likely that the patient will move. It’s a safer, more comfortable treatment experience for the patient.”

For further information email: andre.silveira@elekta.com Volume 10 Issue 6 • January/February 2016

NEWS UPDATE

Leading Cancer Center adopts Varian tumour tracking system as standard for prostate treatments Clinicians in Melbourne have commenced advanced radiotherapy treatments for prostate cancer using a real-time tumor tracking system from Varian Medical Systems. Epworth HealthCare, the largest not-for-profit private hospital group in Victoria, has become the first care provider in Australia to utilize Varian’s Calypso® transponders to enhance precision during image-guided radiotherapy treatments as standard of care.

“The Calypso system gives us information about internal movement of the prostate during treatment that we’ve never had before,” says Anne Perkins, senior medical physicist at Epworth HealthCare. “Reviewing the data for the first five patients we treated shows that the prostate moved outside the limits specified by the radiation oncologist on 20 percent of the treatment visits. The Calypso system can automatically turn off the radiation beam until the

Successful Chemotherapy In The Community Week For Hope For Tomorrow When: 12th – 18th October 2015 From Cake Bakes to NHS Open Days, from Dress Down Days to Tweets, Hope for Tomorrow’s Annual Awareness Week known as CHEMOTHERAPY IN THE COMMUNITY WEEK was a huge success with patients, supporters, NHS medical teams and a supportive network of press contacts throwing themselves into helping to publicise the benefits of chemotherapy closer to home. Our 2nd Annual Mobile Chemotherapy Units (MCU) Partners Day provided an excellent launch to this important event in the charity’s calendar and it was moving to see how much this event has been embraced not only by our existing supporters but just as importantly to a much wider audience beyond. A massive thank you to all our NHS partners who were so helpful in hosting events across the country to help us in our aim of bringing greater awareness to what we do.

MCUs have saved cancer patients over 125,000 hours of travel and waiting times, since our first Unit launched in 2007 in Gloucestershire.

For over 8 years, Hope for Tomorrow’s MCUs have been bringing cancer treatment closer to home for patients throughout the UK. With a total of 9 Units on the road (Gloucestershire, South Wiltshire, Somerset, Hampshire, North Wiltshire, Berkshire, East Kent, Lincolnshire and Cornwall), and more in the pipeline, these Units drastically reduce the stress of driving long distances for appointments, and waiting times, for chemotherapy treatment at main Oncology Centres for both cancer patients and their loved ones.

For further information visit: www.hopefortomorrow.org.uk

prostate returns to its planned position and if necessary radiation therapists can move the treatment couch to reposition the patient before resuming treatment. More than 25 patients have now been treated with Calypso at Epworth.”

“Calypso is a user-friendly system that gives us precise real-time information about the location of the prostate during treatment. Before we had Calypso, we relied on x-ray imaging to determine that our patients were in the correct position for treatment. Calypso is proving to be at least as accurate as x-ray imaging and has the advantage of providing continuous information during treatment, rather than just a snapshot in time.”

For further information contact: Neil Madle, Varian Medical Systems, T: +44 7786 526068, E: neil.madle@varian.com W: www.varian.com

Provectus Biopharmaceuticals Reports Immune Mechanism of Action Data for PV-10 Presented at Society for Immunotherapy of Cancer Annual Meeting Researchers from Moffitt Cancer Center in Tampa, Florida, presented a poster titled, “Intralesional Rose Bengal in Melanoma Elicits Tumor Immunity via High Mobility Group Box 1,” at the Society for Immunotherapy of Cancer (SITC) 30th Anniversary Annual Meeting in National Harbor, Maryland.

Authors Hao Liu, Pasquale Patrick Innamarato, Krithika Kodumudi, Amy Weber, John L Robinson, Satoshi Nemoto, Georgina Crago, Timothy McCardle, Erica Royster, Amod A Sarnaik and Shari Pilon-Thomas state that their “results reveal a clinically relevant immunoadjuvant pathway triggered by tumor cell death secondary to ablation with RB.” The data presented were from nonclinical models of melanoma in mice and clinical data from the team’s recent clinical mechanism of action study (Clinical Trials ID NCT01760499). To view the poster, visit http://www. pvct.com/publications/SITC-Poster-2015.pdf.

In the reported work, the authors showed that tumor-specific T cells were increased in the blood of both mouse and man after tumor ablation with PV-10. This was initiated by tumor cell necrosis, leading to release of High Mobility Box Group 1 (HMBG1), one of a class Damage-Associated Molecular Pattern molecules (DAMPs) released by dying cancer cells that can lead to activation of dendritic cells. HMBG1 release was observed in vitro and after ablation of melanoma tumors in mice and clinical trial participants. This was also correlated with dendritic cell activation and infiltration into lymph nodes draining ablated tumors.

Provectus is currently enrolling patients in a phase 3 study of PV-10 as a single agent therapy for patients with locally advanced cutaneous melanoma (Clinical Trials ID NCT02288897) and in a phase 1b study of PV-10 in combination with the immune checkpoint inhibitor pembrolizumab in patients with metastatic melanoma (Clinical Trials ID NCT02557321).

The complete press release is available at www.pvct.com/pressrelease.html?article=20151105.2

Members of the MCU teams who attended the MCU Partners Day Conference which launched the awareness week.

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NEWS UPDATE

Central Manchester NHS Trust adopts ZedScan™ Central Manchester University Hospitals NHS Foundation Trust has adopted ZedScan™ to improve the speed and accuracy in diagnosing precancerous conditions of the cervix.

The Trust has introduced ZedScan into the Gynaecology department at Saint Mary’s Hospital, Manchester – a centre of excellence for gynaecological oncology, uro-gynaecology and reproductive medicine.

ZedScan™ can measure and detect tissue changes in women identified with an abnormal smear test. The system offers realtime and more accurate detection of precancerous cells than standard colposcopy, enabling clinicians to make better-informed decisions at a patient’s first visit.

ZedScan™, which is available to hospital trusts through a number of purchasing

routes including the NHS Supply Chain, is currently undergoing evaluation at hospital sites throughout the country.

Dr Ursula Winters, Consultant Gynaecologist and lead consultant for colposcopy at Saint Mary’s, said: “The introduction of ZedScan will provide us with the ability to assess women presenting with abnormal cervical smears more quickly and accurately.”

The system, which comprises of a handheld device, software and disposable sensors, was developed by Zilico Ltd. Zilico will exhibit ZedScan™ at the British Society for Colposcopy and Cervical Pathology (BSCCP) Congress in Bradford (April 13th 15th, 2016).

Cepheid Announces International Commercial Availability Of Next Generation Bcr ABL Test

Cepheid has announced the commercial availability outside the United States of Xpert BCR‐ABL Ultra, a quantitative measure of BCR‐ ABL1 mRNA transcripts (types e13a2/ b2a2 or e14a2/b3a2) that allows physicians to monitor the effectiveness of therapy in their patients with Chronic Myelogenous Leukaemia (CML) with enhanced sensitivity.

CML is a cancer of the myeloid lineage of leukocytes (white blood cells) that is characterised by the presence of the “Philadelphia Chromosome”, a reciprocal translocation of chromosomes 9 and 22 that results in the generation of the BCR‐ABL fusion gene. The development of Tyrosine Kinase Inhibitors (TKIs) that target BCR‐ABL has transformed CML from a uniformly fatal illness into a manageable chronic disease for many patients, and new data now suggest that for a subset of patients with consistently deep molecular response (at least a 4.5 log reduction from baseline levels of BCR‐ABL1 transcript), TKI therapy might be discontinued altogether without further recurrence of the disease.

“Until now, tests for BCR‐ABL were not standardised and could not be reliably compared in one lab, and certainly not across borders, making patient management quite challenging.” said David Persing, MD, PhD, Cepheid’s Chief Medical and Technology Officer.

For further information visit: www.zilico.co.uk

Siemens Healthcare launches new PET/CT system Siemens Healthcare has launched the new versatile and cost-effective Biograph Horizon™ PET/CT system, which offers premium performance at an attractive total cost of ownership. The system provides clinicians with the capabilities required to serve a broad range of patients and expand into new service areas. It enables the use of all commercially available PET tracers, giving users the ability to address more indications in the specialist fields of oncology, neurology and cardiology.

The Biograph Horizon utilises 4mm LSO crystals to provide rapid scintillation with a high-light output, providing excellent image quality using the lowest achievable dose to aid clinicians with visualising small lesions.

This in turn ensures a timely diagnosis which contributes to effective care pathways, helping to reduce patient side effects related to ineffective therapies. The system also offers built-in capabilities that automate routine tasks to increase productivity and streamline workflows. The Quanti•QC runs quality control procedures overnight to save precious clinic time, while scans can be performed in under five minutes, and reconstruction runs alongside acquisition for image delivery just

30 seconds after the scan.

Steve Holmes, Sales Director at Siemens Healthcare states, “The Biograph Horizon provides a cost-effective PET/CT imaging solution that does not compromise on quality.

As our smallest PET/CT system, it offers low power requirements and a small footprint to ensure reduced operating and maintenance costs, with the flexibility to meet expanding clinical needs.”

For more information, visit www.cepheid.com

Visit: www.siemens.co.uk/healthcare

Brain Tumour Research appoints first Director of Research The national charity Brain Tumour Research has appointed its first Director of Research, Dr Kieran Breen. He will have a key role in establishing a further three Centres of Excellence as well as developing and implementing the charity’s research strategy to maximise the impact of the research being carried out at its existing four centres.

He will also be responsible for ensuring the Centres work together as a network within the appropriate governance and review procedures. This will include ensuring that the research funds are attracting additional 202

support for the scientists from other funding sources.

Dr Breen said: “I am thrilled to be taking up this role at such an important time for Brain Tumour Research. It is crucial that the charity’s supporters are kept informed of the world class research being carried out at our Centres and communication of the research outcomes will be a key part of my role.

Chief Executive of Brain Tumour Research,

Sue Farrington Smith, said: “We welcome Dr Breen who will be a great asset to our team. His role in overseeing the research we fund and in ensuring good communication of this in the UK and further afield is crucial as the charity grows in size and influence.”

For further information visit: www.braintumourresearch.org Volume 10 Issue 6 • January/February 2016

NEWS UPDATE

Varian and Apollo Group Sign Educational Partnership to Develop Radiotherapy Caregivers in India Varian Medical Systems has signed a Memorandum of Understanding (MoU) to develop an educational partnership with Apollo Hospitals Group, the largest hospital chain in India, to introduce a program that will help train radiation technologists in the country. The MoU was signed

by Dr K Prabakar, chief executive officer of Apollo Knowledge, and Ashok Kakkar, Varian’s India managing director, in Hyderabad.

In the first radiotherapy partnership of its kind between industry and a care provider in India, Varian intends to deploy its Access to Care program by leveraging the existing Apollo Knowledge network that comprises of several educational entities in the healthcare space in India. Access to Care is an educational program that seeks to bridge the gap between the growing need for modern radiotherapy treatment machines in developing countries and the lack of trained personnel to operate them.

“The world is seeing an alarming increase in the cancer burden and it is important that the healthcare industry stakeholders join hands to

ensure that we have the required number of skilled clinicians,” said Dr Prabakar. “I am convinced that this collaboration is the right step forward in this direction, bearing in mind the respective strengths of Apollo and Varian.”

For further information contact: Neil Madle, Varian Medical Systems, T: +44 7786 526068, E: neil.madle@varian.com W: www.varian.com

UK men could risk lives by ignoring common bowel cancer symptoms One in five men in the UK would not immediately think to visit their GP after experiencing one or more of common symptoms of bowel cancer for three weeks, putting their lives at risk from late diagnosis, a new survey reveals.

Experiencing health issues such as a persistent change in bowel habit, abdominal pain, a stomach lump or unexplained weight loss or tiredness for three weeks would not prompt 20% of men to make an appointment with their doctor.

Even adding the ‘red-light’ warning of bleeding from the bottom or blood in your poo to a list of symptoms would not motivate 16% of those questioned to get checked out after three weeks.

The research was carried out by YouGov for the charity Beating Bowel Cancer, as men around the country lay down their razors to participate in the charity’s fundraising Decembeard campaign.

Men who have all been affected by bowel cancer and who are supporting the Decembeard campaign.

For more information about Decembeard or to sign up, go to www.decembeard.org. You can also check out the campaign @Decembeard_UK #decembeard.

Stratech Scientific Ltd – new UK distributor for Avanti Polar Lipids Inc. Stratech Scientific Ltd is excited to have been appointed the new UK and republic of Ireland distributor for Avanti Polar Lipids.

Avanti offer an outstanding range of lipids, detergents, mass spec standards and tools for lipid/protein and interaction determination. They have a global reputation for quality and purity built up over more than 40 years, making their products an excellent choice for UK scientists.

Their catalogue inventory lists over 2,000 research products, along with a full range of services for drug development customers. These include process chemistry & scale-up manufacturing all in FDA inspected premises under GMP. Their current product range consists of: • Sphingolipids • Phospholipids • Sterols • Bioactive Lipids • Coenzyme A & Derivatives • Fluorescent Lipids • Neutral Lipids • Detergents • AuroraTM Gold Probes The full range of Avanti products is available to view, with pricing on our website:www.stratech.co.uk For further information or quotations, please do not hesitate to contact us at info@stratech.co.uk or T: +44 (0)1638 782600.

Oncology News Dec15_Oncology News Dec15 15/12/2015 13:51 Page 1

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Bringing sensitivity to bowel cancer screening

“In conclusion, faecal M2-PK, either as an ELISA or as a lateral rapid flow test, is a cost-effective and easy-to-perform routine test.” Tonus, C. et al. World J Gastroenterology, 2012.

Can detect non-bleeding, as well as bleeding, polyps and tumours.

Further information from: Ivor Smith, ScheBo • Biotech UK Ltd, PO Box 6359, Basingstoke, RG22 4WE ®

Tel: 01256 477259

Fax: 01256 327889

Volume 10 Issue 6 • January/February 2016

E-mail: i.smith@schebo.co.uk

www.schebo.co.uk

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Deliver Lung SBRT in 43% Less Time

4513 371 1229 11:13

Sophisticated respiratory motion management without compromised treatment times

One Solution. Unlimited Possiblities.

www.VersaHD.com As compared to previous generation Elekta digital linear accelerators. Stieler F, Steil V, Wenz F, Lohr F, Department of Radiation Oncology, University Medical Center Mannheim, University of Heidelberg, Germany.

Versa HD is not available for sale or distribution in all markets. Please contact your Elekta representative for details.