Innovations in Oncology Q4 Dec-2019

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I couldn’t have imagined the successes we are seeing from immunotherapy Scientists are further exploring checkpoint inhibitors and cell therapies as ways to use immunotherapy on a larger scale in the fight against cancer.

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he way we treat cancer has progressed over recent years and immunotherapy has had a big impact in allowing patients’ immune systems to uncover and at tack ca ncers t hat may have previously gone undetected. When I first started researching the potential of immunotherapy as a cancer treatment, I don’t think I could ever have imagined how much of a difference immunotherapy would be making for people with cancer now. Cancers that were considered incurable are now being so successfully treated with immunotherapy that patients who have had multiple, widely-spread tumours of some types, are now liv ing for many years w ith no evidence of active disease. Our immune system is good at killing cancer in theory, but cancer has evolved many different ways to evade and hide from the body’s natural defenses; what is clever and different about immunotherapies is that they are designed to help unmask the cancer and encourage the immune system to attack.

How do the checkpoint inhibitors and cell therapies work? So-cal led ‘im mune checkpoint inhibitors’, are examples of this kind of treatment. The immune system has ‘on’ and ‘off’ switches to make sure it is effective against infection, but does not become so uncontrollably overactive that it ends up harming the body’s own healthy tissue. Cancer has found ways to stimulate t he of f s w itche s (or neg at ive immune checkpoint proteins), to help the cancer hide in plain sight. The checkpoint in hibitor treatments work by inhibiting these off switches co-opted by the cancer – cancer then has nowhere to hide. And the results of clinical trials of many of these treatments have been remarkable. Checkpoint inhibitor treatments made t heir brea kt hrough in mel a nom a, b ut a re now a l s o ava i lable a nd ef fec t ive i n, for example, lung, head and neck cancer and bladder cancer, and are being trialled in other tumour types.

WRITTEN BY: PROFESSOR ALAN MELCHER Professor of Translational Immunotherapy The Institute of Cancer Research, London, The Royal Marsden NHS Foundation Trust

Our immune system is good at killing cancer in theory, but cancer has evolved many different ways to evade and hide from the body’s natural defenses. CAR-T cell therapy is far more personalised, complex and expensive but very effective The other headline-grabbing form of immunotherapy is cell therapies such as ‘CAR-T cells’. The early trials were in some ways as impressive a s t he che ck p oi nt i n h ibitors. However, such cell therapy is also far more complex and personalised than checkpoint inhibitors – a patient’s own immune cells must be extracted, trained to spot cancer cells by genetic alteration, and then put back so they can hunt down and kill the cancer. In addition, this treatment is only effective in, and available for, some forms of blood cancer – we are yet to see it work on solid tumours. But it is so effective that, despite its very high cost, NHS England has agreed to pay for CAR-T in the small number

of children and young people with acute lymphoblastic leukaemia, when chemotherapy has not worked. As with all immunotherapies, but particularly for CAR-T, it is early days – we do not yet have long-term survival data and do not know whether there are any later side effects. Despite all the headline-grabbing clinical trial results and the amazing s tor ie s of i nd iv idu a l p e ople’s treatment, we still don’t really know exactly how immunotherapies such as checkpoint inhibitors work, the ways patients could benefit most and, importantly, how to get them to work in more tumour types. So what do we need to do next to make immunotherapy a viable treatment for many more patients?

Combination strategies, combining immunotherapies with other, more traditional, cancer treatments, c ompl ic at e t h i n g s f u r t he r. Radiotherapy and chemotherapy, c a n, i n s ome c i rc u m s t a nc e s, t r i g g e r a n i m mu ne r e s p on s e that helps immunotherapy work. Howe ve r, a n a l m o s t i n f i n it e nu m b e r of c om b i n at ion s a r e possible, and we need to develop informed, scientifically validated strategies, which may particularly help in tumour types in which i m m u n o t h e r a p y h a s n o t ye t proved successful. While we are making great strides in treating patients with the new generation of immunotherapies, and immuno-oncology is evolving i nto a completely new ca ncer treatment paradigm, we, as doctors and researchers, want to see these treatments benefit as many patients as possible. A nd, w ith fur ther research, work ing toget her as laboratory and clinical scientists, the future looks bright. Read more at healthawareness.co.uk

Jobcode: NOUK1901303-08 Date of Prep: November 2019

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Translating research into life-saving outcomes for patients WRITTEN BY: PROFESSOR ARNE AKBAR President, British Society for Immunology

Harnessing the immune system to treat cancer has seen much success, but challenges remain. How can we create the right environment to maximise its life-saving potential for patients?

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mmunolog y has f lourished i n recent yea rs, w it h new d iscover ies a l low ing us t o u n d e r s t a n d i t s e x t e n s i ve involvement in maintaining health and the consequences that occur when these processes go awry. This is particularly true in the field of cancer where the advent of immunotherapy has given new hope to patients and captured t he i mag i nat ion of doc tors and scientists. Immunotherapy was first explored in 1891 The f i rs t s ug ge s t ion t hat t he i m mu ne s ystem m ig ht play a role in treating cancer came as early as 1891, when the surgeon, William Coley, treated a patient with a tumour on his tonsil by injecting it with bacteria to elicit an immune response. The tumour began to break down and the patient lived for another eight years, showing that localised activation of the immune system could combat malignancy.

Unleashing the immune system to attack tumours

remission in those who previously had few therapeutic options.

More recently, our understanding of how to harness the immune system to treat cancer was significantly accelerated by Jim A llison and Tasuku Honjo. They discovered that the PD-1 protein acts as a ‘brake’ on immune cells, stopping them from attacking normal cells. Cancer cells hijack this mechanism to hide from the immune system. By using a checkpoint inhibitor to block the interaction of PD-1 with PD-L1 expressed on cancer cells, the immune system can be unleashed to attack tumours. Other areas of cancer immunotherapy have also hailed significant successes in recent years; including the use of a checkpoint inhibitor to treat melanoma. The use of engineered chimeric antigen receptor (CAR) expressing T ly mpho c y te s to t re at s ome leukaemias and lymphomas has also proved revolutionary for a subset of patients, achieving high levels of

Immunotherapy doesn’t work for brain, prostate or pancreatic cancers However, t he s tor y of c a nc er i m mu not herapy i s not one of unmitigated success. Despite the hype, existing immunotherapies don’t work for ma ny pat ient s and numerous questions remain unresolved. Some trials that initially carried great hopes led to patients developing unforeseen and, in some cases, serious side-effects. Furthermore, current immunotherapy approaches don’t work for some cancer types, such as brain, prostate or pancreatic. Collaboration to drive research forward We mu st promote i nterac t ion between researchers and clinicians in the field to facilitate translational research activity. The UK has all the ingredients needed, including

With over 350,000 new cases of cancer diagnosed in the UK each year, it is imperative that we move quickly to translate our endeavours into life-saving outcomes. infrastructure, investment and skills, to allow cancer immunology research to thrive. The British Society for Immunology recently launched a new partnership with the National Cancer Research Institute to bring immunologists, cancer scientists and clinicians closer together. B y j o i n i n g fo r c e s , we a i m to faci l itate dia log ue bet ween t hese g roups to dr ive for ward new collaborations that address challenges in immuno-oncology and advance understanding of the complex interactions between cancer and the immune system. Establishing these links to speed up discovery in the clinical research space will enable fresh thinking to refine approaches on how to harness t he i m mu ne s ystem to t a rget individual cancers. Knowledge sharing is also a key

part of the initiative, allowing oncolog ists to keep up to date with the latest thinking on how immunotherapies work and how they cause side-effects. This will allow doctors to treat, not just the symptoms of these side effects, but also target the cause, hopefully leading to more effective therapies. With over 350,000 new cases of cancer diagnosed in the UK each year, it is imperative that we move quickly to translate our endeavours into life-saving outcomes. We must break down barriers of com mu n icat ion bet ween research communities to deliver the transformative potential of immunotherapy to more patients living with cancer. Read more at healthawareness.co.uk

The Human Body is

Remarkable. It inspires our mission to discover, develop and deliver innovative medicines that help patients prevail over serious diseases. www.bms.com/gb

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Artificial intelligence – great potential to reduce inefficiencies, errors and cost Cancer detection in women may be more efficient and affordable with the use of artificial intelligence. However, more research is needed to address its real-world applicability and safety.

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ancer early detection requires examination by a trained health provider using different imaging techniques, endoscopic exa m i nat ion s a nd pathological investigations. Irrespective of the methodology, the detection of diseases in medical science is often subjective. This is true for women’s cancer and precancer detection and poses two major challenges. F irst ly, a cer tain number of misdiagnosis is inevitable due to interpretation error. The second and more formidable challenge is to get an adequate number of trained personnel, the need for which is growing exponentially. Artificial Intelligence (AI) has the potential to automate detection, improve accuracy, enhance efficiency and reduce healthcare costs. A computer processing 250 million images may cost as little as $1,000. How does AI work to detect cancer? Image recog n it ion sof t ware programmes can be ‘trained’ to detect patterns by processing massive datasets using a variety of artificial neural network (ANN) configurations.

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ANN requires digitised inputs in the form of supervised learning, which allows the computer to detect features with increasingly high confidence and ultimately, be able to detect/predict the abnormalities accurately. ANN can help interpret vital signs, skin changes, ECGs, medical scans, endoscopy images, pathology slides – the possibilities are endless. AI can act as ‘double reader’ in place of a second radiologist M a m mog raph ies may be u se d for brea st c a ncer sc re en i ng and for the detection of disease i n s y mp t om at ic wome n . The assessment of mammograms is prone to both reading error (failure to detect abnormality) and decision error (incorrect interpretation). Mammograms miss up to 30% of the cancers. Independent reading by t wo radiologists, which is recommended to reduce error, increases the burden on the radiology services. ANN has been used to complement a radiologist as a ‘double reader’. AI technology has yet to demonstrate conclusively the capacity to out-

WRITTEN BY: DR PARTHA BASU Head, Screening (SCR) Group, International Agency for Research on Cancer, (World Health Organisation) Lyon, France

Nearly 15% of breast biopsies performed because of abnormal mammograms are stamped as ‘high-risk’ conditions, and are essentially benign. perform a trained radiologist. Nearly 15% of breast biopsies performed because of abnormal mammograms are stamped as ‘high-risk’ conditions, and are essentially benign. Women undergo breast surgery just because the true malignant potential of such conditions is uncertain. The development of validated AI algorithms is likely to be able to accurately risk stratify such patients based on clinical and laboratory data. This should allow us to avoid unnecessary surgeries.

confirm the diagnosis. Colposcopy is highly subjective. The examination is therefore error-prone and may be improved with the use of AI. An algorithm developed by the US National Cancer Institute identified pre-cancer/cancer using several thousand cer vical images. The system achieved greater accuracy than human interpretation of an image or Pap smear.

AI in cervical cancer screening avoids subjective readings

Individuals positive on screening test for colon cancer or having s u s pic iou s s y mptom s re qu i re colonoscopy to detect polyps (many are precancerous) or cancer. AI can identify very tiny polyps in the colon during colonoscopy with better accuracy and speed than manual detection by an endoscopist.

Screen i ng for cer v ica l ca ncer traditionally used Pap smear. Women with a positive smear are usually referred to colposcopy (visually examines the cervix under light i l lum inated mag n ificat ion) to

Colon cancer could be improved with AI

Caveats A d v a nc e s i n A I deve lopme nt must match the anatomic and pathologic complexities of health and disease. There are ethical and legal issues around the ownership of responsibility for any harms resulting out of ‘technological failures’ or compromised privacy. Questions remain about whether health-prov iders w ill be made redundant as AI replaces many of the critical decision-making and will medical-care lose the human touch? Perhaps not. The accuracy and efficiency of AI with appropriate oversight of algorithmic interpretations by a skilled provider may provide the best approach to deliver efficient and equitable future healthcare. Disclaimer As personnel of the International Agency for Research on Cancer / World Health Organization, the author alone is responsible for the views expressed in this article and he does not necessarily represent the decisions, policy or views of the International Agency for Research on Cancer / World Health Organization.

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What is innovation in cancer without outcomes? Cancer is a societal issue. While significant advances have been made, it remains a growing public health threat.

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ne in two UK people will be diagnosed with cancer in their lifetime 1 and it has now surpassed cardiovascular disease as the number one killer of UK citizens2. Data shows that the economic toll of cancer is more than that of cardiovascular disease and other prevalent illnesses, as a greater number of adults die from cancer during their peak working and parenting years3. Innovation in cancer is helping to improve outcomes, providing more treatment options, offering extended survival, and improving quality of life for patients and their carers. Progressive methods by UK health agencies including t he Cancer Drug Funds 4, the Early Access to Medicines Scheme (EAMs), and the Fast Track Assessment pathway 5, have allowed the UK to have one of the shor test times bet ween European marketing authorisation and national reimbursement in the European Union5. Nova r t i s Oncolog y ha s seen this first hand: our post-surgery sk in cancer t reat ment was

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available on the National Health Service (NHS) just five days after marketing authorisation, and our CAR-T therapy – the first of its kind for a paediatric blood cancer – was available after only two weeks. Cancer survival in the UK is one of the lowest within the EU H o we ve r, w h i l e t h e s e f a s t e r t i mel i nes enable qu icker N H S funding of innovative treatments, including advances in surgeries and radiotherapy, cancer survival in the UK remains one of the lowest in Europe – for example the UK five-year survival for patients with colon cancer is less than Ireland and only just above Estonia, Latvia and Lithuania6. One ea s y a n s wer may se em to b e i nve s t ment – t here a re consistent headlines about NHS underfunding – but in reality there are multiple reasons for this gap between access to innovation and cancer outcomes. A clear cha l lenge is early diagnosis. An analysis this year by Cancer Research UK estimated that around 115,000 cancer patients each

year in England are diagnosed too late to give them the best chance of survival, with nearly half of all cancers diagnosed at stage 3 or 47. More staff for screening could improve cancer-survival Up to a fifth of patients are diagnosed in an emergency setting, versus referrals through screening or their GP. Not only does this impact treatment options and potential survival, but patients diagnosed this way also report a worse experience of cancer care2. Staff shortages also contribute to late diagnoses, as any increase in referrals can overwhelm a system with wide-spread vacancies. For example, in England, best practice states that 85% of people who have been urgently referred by their GP for suspected cancer should begin their first treatment within two months. This number has been consistently missed since 2014, and is currently only around 79%2. Further innovation could improve country-wide disparity in cancer care

WRITTEN BY: DEBORAH LANCASTER Head of Market Access, Novartis Oncology, UK

E v i d e n c e a l s o s u g g e s t s t h at variations in care across hospitals mean not all cancer patients receive the best possible treatment2. Despite the improved timelines to secure NHS funding, the uptake of innovative treatments is different between hospital centres. Plus, hurdles in sharing best practice can mean innovations are not picked up quickly by other hospitals. The prog ress i n d ig it i sat ion of medical records, and linking of patient datasets, w il l al low resea rchers to have g re ater knowledge of the patient experience – potentially highlighting those areas which could most improve outcomes. Though on ly one adv a nc e, it demon s t rate s one opportunity to improve cancer patient care and potentially reduce avoidable cancer deaths. Cancer needs to be recognised as a national priority

as we enter this new decade. Every UK cancer patient deserves the chance to achieve their best possible outcome. ONC19-C136; December 2019 Sources: 1. Cancer Research UK ‘Cancer risk statistics’. Available at https://www.cancerresearchuk.org/health-professional/cancer-statistics/risk. Accessed December 2019. 2. Cancer Research UK (2019). ‘Cancer in the UK 2019’. Available at: https://www.cancerresearchuk.org/sites/default/files/state_ of_the_nation_april_2019.pdf. Accessed December 2019 3. PhRMA Report (2010). ‘The Global Economic Impact of Cancer’. http://phrma-docs.phrma.org/sites/default/files/pdf/08-172010_economic_impact_study.pdf. Accessed December 2019. 4. England, NHS. ‘Appraisal and Funding of Cancer Drugs from July 2016 (including the new Cancer Drugs Fund)’. Available at https://www.england.nhs.uk/wp-content/uploads/2013/04/cdfsop.pdf. Accessed December 2019. 5. Deloitte (2019). ‘Patient Access to Innovative Medicines in Europe’. Available at https://www2.deloitte.com/content/dam/ Deloitte/cz/Documents/legal/deloitte-uk-patient-access-to-innovative-medicine-in-europe.pdf. Accessed December 2019. 6. Cancer Research UK (2019). ‘Lack of government action on NHS staffing undermines ambition to diagnose cancer early’. https://www.cancerresearchuk.org/about-us/cancer-news/ press-release/2019-09-02-lack-of-government-action-on-nhsstaffing-undermines-ambition-to-diagnose-cancer-early. Accessed December 2019. 7. England, NHS (2019). ‘The NHS Long Term Plan”. https:// www.longtermplan.nhs.uk/wp-content/uploads/2019/08/nhslong-term-plan-version-1.2.pdf. Accessed December 2019.

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To truly make an impact, cancer needs to once again be recognised as a national priority – one worthy of its own national long term action plan

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Data-driven medicine is in the House: cancer becomes personal WRITTEN BY: GIOIA ALTHOFF VP Genomics, SOPHiA Genetics

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ouse M.D. is my g uilt y pleasure – it’s hard not to love watching a good medical mystery solved by grouchy genius Dr Gregory House approaching diseases like a detective. Now consider the show from a patient’s point of view; imagine the pain, anxiety, and uncertainty they experience when faced with the disease, under the care of real-world doctors who sometimes don’t have all the answers. C a ncer has been one of t he biggest mysteries of our time; it’s unpredictable, ever-evolving and difficult to solve. Medical practitioners need all the help they can get to tackle this disease. So, what if we had the technology to make the cancer journey less burdensome for everyone involved?

Combining multi-modal sources of data could propel our understanding of cancer

Starting with genomics to pinpoint mutations

Our solution? A global AI knowledge sharing platform

Data-driven medicine is key to fighting cancer; its adoption within hospitals helps alleviate the burden of complicated and expensive medical journeys, while providing important benefits to patients. Sta r t i ng w it h t he core a rea of genomics, it allows accurate pinpointing of the specific mutations responsible for cancer to better diagnose patients and support therapeutic decisions. However, relying on a sole source of data isn’t enough. To better solve cancer cases – and ultimately save lives – a global approach is necessary. Clinicians should be able to utilise, manage, and learn from all relevant medical information available to grasp the bigger picture. It goes beyond genomics with radiomics, i.e. t he ex traction of valuable information from standard medical imaging, such as PET scans and MRI.

The SOPHi A AI-based platform empowers clinicians to accurately dete c t sp e c i f ic c a ncer-relate d mutations and allow them to share their knowledge globally in a secure way, so that data used to help a patient in London today will benefit another in Manilla tomorrow. Supporting clinicians in their therapeutic decision-making, it has already supported the diagnosis of over 430,000 patients worldwide. The power of data-driven medicine is bringing us into a future where we can manage cancer, making the pain, anxiety, and uncertainty of patients’ journeys a thing of the past and House M.D. a historical fiction.

Combining genomics and radiomics enables unique capabilities in oncology, providing multidimensional understandings of cancer to improve diagnosis and prognosis, anticipate tumour e volut ion , id e nt i f y p o te nt i a l treatment options and monitor treatment efficacy. As Dr House relies on his team, similarly, we at SOPHiA GENETICS understand that collaboration is essential. Leading the global adoption of data-driven medicine worldwide, we’ve created a communit y of over 1,000 hospitals - an expertise that goes beyond the scope of Dr. House’s ward.

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Why AI could mean a big change for cancer management A data-driven approach to healthcare has the potential to speed up diagnosis and guide more effective, personalised treatments. It could have huge benefits in the field of oncology.

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ome cancers can be difficult to detect, largely because sy mptoms are not always obvious in their early stages. “Many cancers that arise in deepseated organs — such as the pancreas — may not announce themselves clinical ly until t hey are wel ladvanced,” says Dr Tom Mikkelsen, Medical Director of the Precision Medicine Program at the Henry Ford Health System in Detroit, USA. “Until now, physicians have had to witness a change in symptoms over time, or notice a pattern that announces itself as cancerous.” Personalised and more efficient diagnosis However, data-driven medicine — powered by artificial intelligence (AI) — means that healthcare is entering a dynamic new era: one that is personalised, more efficient and with the potential to make a positive impact on diagnosis and treatment. As such, it could have huge benefits in the field of oncology. There’s certainly no shortage of medical data to analyse. “On the DNA side, there’s an avalanche of information,” says Dr Mikkelsen. “ Th is includes data about t he mutations a tumour carries, in what fraction of the cell the mutation persists when the tumour reoccurs, and how the tumour has escaped therapy.” On top of this there’s more standard medical information about a patient’s contact with their physician over the years, and lab results such as blood tests, etc. Possibility of better outcomes for patients

Close analysis of personal medical data may help speed diagnosis and trigger earlier interventions which are more likely to result in a positive outcome for individual patients. For example, someone who may be genetically predisposed to certain types of cancer might be surveyed more closely, either with intensive screening or — hopefully soon — with a new diagnostic methodology called liquid biopsy, which can detect mutations from cancer cells in the blood. “Liquid biopsy is in its early stages, but is an incredibly exciting development,” says Dr Mikkelsen. A data-driven approach can also result in more effective treatments. “If specific mutations are matched with specific drugs, it means that patients are more likely to receive therapy that they will respond to positively, and without adverse side-effects,” says Dr Mikkelsen. “Essentially it allows for a more tailored and focussed treatment, based on information about an individual’s specific cell mutations.” This breakt hrough has been made possible thanks to artificial intelligence algorithms which can discover patterns in vast amounts of existing medical data, allowing medical professionals to make better decisions and more informed predictions. Dr Mikkelsen urges a note of caution, however, because this technology is only as good as how we ‘human’ train it and thanks to the quality of data we put into it.

quality, reproducible, uniform data gleaned from large populations. So it might sound mundane, but it’s critical for healthcare professionals to ensure that all data — from clinical examinations right through to how medical records are documented — is standardised.” He also stresses the need for a global approach to data-driven strategies. “The teams involved in this research are international but they all need to be talking the same language,” he says. “Their collaboration is crucial because no single institution can gather enough information on, say, a rare cancer cell mutation that only exists in one or two per cent of a population. They have to work together to share their knowledge in order to properly identif y those patients and so improve the value of therapy.

Need for collaboration on a global scale

WRITTEN BY: TONY GREENWAY

INTERVIEW WITH:

DR TOM MIKKELSEN Medical Director of the Precision Medicine Program at the Henry Ford Health System, Detroit, USA

“AI is not magic,” he says. “Machine learning can only be done with valid,

Cancer becomes personal Learn more at sophiagenetics.com

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Info box With unparalleled NHS expertise and outstanding industry knowledge, Wilmington Healthcare offers data, data visualisation, insight and analysis on a variety of UK healthcare fields. We deliver sustainable outcomes for NHS suppliers and ultimately patients. To see more of our data and insights on cancer staging, visit wilmingtonhealthcare.com/ oncology or contact:

info@wilmingtonhealthcare.com

A late stage killer: why early diagnosis is so important The NHS’ Long Term Plan places cancer at the heart of its agenda. Local systems have been given ambitious targets to improve screening, diagnosis and survival rates and their forthcoming operational plans must demonstrate how they will achieve this.

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wo key targets in the Long Term Plan are: by 2028, the proportion of cancers diagnosed at stages 1 and 2 will rise from around half to three-quarters of cancer patients; and from 2028, 55,000 more people each year will survive their cancer for at least five years after diagnosis. These two targets should be thought of as interlinked, as all the evidence suggests that early diagnosis leads to greater chances of survival. To make this a reality, the Long Term Plan has proposed developing transformative workstreams: rolling out lung MOTs to detect lung cancer earlier in at-risk populations, and introducing a nationwide network of rapid diagnostic centres for people with serious but not specific symptoms that could be cancer. Why single out lung cancer, and why might the rapid diagnostic centres be such an important part of this? Wilmington Healthcare has carried out an a n a lys i s of c a nc er s t a g i n g d at a, a nd it b e g i n s to tel l a compel ling stor y about problems in lung cancer diagnosis. If your lung cancer is diagnosed at stage 4, your survival is already heavily compromised. The five-year rate for such patients is less than 10%. At stage 3, survival is between 25% and 35%. Yet our first data visualisation (Figure 1) indicates that you are more likely to receive a lung cancer diagnosis at stage 4 than

at any other stage. It also shows that lung cancer in particular, is susceptible to late diagnosis, compared with, for example, colorectal cancer, which has seen improvements in screening via the provision of home bowel kits and a major public awareness campaign. This highlights a fundamental challenge for the systems: how to find the patients that need early treatment? This is where the lung MOTs and rapid diagnostic centres (RDCs) can come into their own. Proactive and preventive lung health checks are likely to catch more cases at stages 1, 2 and 3; whereas the RDCs can fast-track primary care referrals where there is GP uncertainty – early signs of lung cancer, for example, can involve symptoms that resemble a common cold - and rule out or confirm cases at the earliest possible stage. Our second visualisation (Figure 2), shows national trends in diagnosing cancer at various stages. Here you can see that there has been little to no progress in reducing the number of lung cancers detected at stage 4, and it has remained the most common diagnostic stage over the past decade. Thirdly and finally, Figure 3 shows variation of diagnostic stage by regional cancer alliances. From the data here we can build a regional picture on cancer stage. You can see that there is almost a ten percentage point gap between the area where

WRITTEN BY: OLIVER HUDSON Content Director, Wilmington Healthcare you are most likely to be diagnosed at stage 4 – East of England, South – and least likely – Greater Manchester. This postcode lottery of staging diagnosis should have cancer policymakers concerned when we know survival is so dependent upon it. It is also a fair question to ask – what is Greater Manchester doing differently? It may come as no surprise that rapid diagnosis has made a leap forward in the devolved authority there. The Greater Manchester lung cancer pathway has used a £1.3 million transformation fund investment secured in autumn 2018 to run accelerated pathways performing complex diagnostic and staging work through high volume diagnostic hubs. The programme won a prestigious HSJ award last year. Local decision makers will need to show ambition like this if the targets of the Long Term Plan are to be met, and if we are to make progress in reaching and treating patients with cancer before their likelihood of survival is diminished.

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Improving survival in bowel cancer patients Bowel cancer is the fourth most common cancer in the UK, with 42,000 cases diagnosed per year. It is treatable and curable if diagnosed early, but only 10-15% present early enough.

WRITTEN BY: DR AFSANA ELANKO Director of Education, British Association of Surgical Oncology (BASO - The Association for Cancer Surgery)

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he 5-year survival for colon and rectal cancer remains at 65% and 67% respectively. Over 20% of cases present very late with locally advanced or metastatic disease making cure less likely. The key challenge for surgeons remains the early diagnosis, and staging followed by precision surgery to ensure complete cancer resection. Signs of early bowel cancer Early colorectal cancer is asymptomatic and can only be detected with screening. Commonly used screening tests are feacal occult blood (FOB) test and Faecal Immunochemical Test (FIT) with varying degrees of sensitivity and specificity. In FOB testing three stool samples are needed and the central screening hub for the region analyses the results and if positive the patient is called for colonoscopy. Out of 10 patients undergoing

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The key challenge for surgeons remains the early diagnosis, and staging followed by precision surgery to ensure complete cancer resection. colonoscopy for this reason, only 1-2 may have a colorectal cancer. FIT is far more specific for human blood in stool and only 1 test is needed and those who score positive are invited for endoscopic screening. Endoscopy prov ides the best assessment and diagnosis of colonic polyps and cancers. A recent pilot is investigating the role of a one-stop flexi-scope bowel cancer screening with a f lexible Sigmoidoscopy, which can rule out over 70% of colorectal cancers. New developments that may improve prognosis

Robotic colorectal cancer surgery has shown improved outcomes for patients, as precision surgery with enhanced views and endo wrist instrumentation can lead to better cancer resection and improved survival. This also has the potential to reduce the need for chemotherapy and radiotherapy in a select group of patients. With the recent advances in digital surgery, there is huge potential for intraoperative navigational tools that can enormously help the surgeon to ensure complete cancer removal. Currently this type of surgery is more expensive, has limited availability of

experts; but the situation is likely to change over the next 5 years. What about chemotherapy and immunotherapy? C hemot her apy c a n i mprove s u r v iv a l i n c olore c t a l c a nc er when used for advanced cancers or those with worse prognosis. Currently a combination of different chemotherapy agents for a period of 3-6 month duration is used. Research cont i nues to f i nd t he cor re c t combination, the ideal duration of treatment and the selection of patients who will benefit the most from chemotherapy. Immunotherapy is also a newer development showing promising results in various cancers and its role in the management of advanced colorectal cancers is currently under review. Some examples include: 1. Immune checkpoint inhibitors

WRITTEN BY: MR JIM KHAN Consultant Colorectal Surgeon, Clinical Director, Portsmouth Hospitals NHS Trust, Trustee BASO - ACS - Can be used for patients whose cancer cells have tested positive for specific gene changes, e.g. changes in one of the mismatch repair genes or high level of microsatellite instability. Usually given to patients whose cancer is still growing post chemotherapy, but can be used in patients whose cancer is not resectable, has reoccurred post treatment or metastasized. 2. PD-1 Inhibitors – These drugs help to boost t he im mune system against cancer cells by targeting a protein (PD-1) on the T cells that normally prevents these cells from attacking other cells in the body. 3. C T L A - 4 I n h i b i t o r – A l s o work s by boosting t he immune system, but it blocks a d i f ferent protei n on t he T cells. MEDIAPLANET


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How risk-adapted radiotherapy is revolutionising breast cancer care

INTERVIEW WITH:

Oncologists now take a ‘risk-adapted’ approach to breast cancer treatment, in order to better tailor therapies to individual patients, says a leading cancer specialist.

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his is an exciting time to b e work i n g i n t he f ield o f b r e a s t c a n c e r,” s ay s Dr I mogen L ocke, Con s u lt a nt Clinical Oncologist at The Royal Marsden NHS Foundation Trust. Ground-breaking innovations are personalising cancer treatment and improving patients’ quality of life. “Historically in breast cancer radiotherapy, for example, all breast cancer patients would undergo bro ad ly s i m i l a r r ad iot her apy treatments, whether their prognosis w a s g o o d o r p o o r. H o we ve r, advances in genomic medicine have helped oncologists unlock their understanding of breast cancer biology so that treatment can now be ‘risk-adapted’ to each individual, so that patients aren’t under or over treated.” Better treatments delivered in more sophisticated ways “ R i s k- a d a p t e d r a d i o t h e r a p y

recognises that breast cancer is not one disease, but a whole spectrum of diseases with different prognoses,” says Dr Locke. “By looking at the molecular subtype of a person’s cancer, as well as the stage of their cancer, we can assess each patient’s risk of recurrence following surgery — ver y low, low, inter mediate or high — and therefore which radiotherapy strategy will be best for them.” This means that some women with low-grade breast cancers may not need to have radiotherapy, which can cause side-effects such as tiredness, sore skin, and breast discomfort, at all. Or that low-risk patients, who do need treatment, may be better suited to partial radiotherapy, which pinpoints the area of their breast most at risk of recurrence. “We can also deliver radiotherapy in increasingly sophisticated ways,” says Dr Locke. “Techniques such as intensity-modulated radiotherapy can target a tumour more

precisely without compromising healthy tissue.” There have also been important surg ica l brea kt h roughs. For instance, when patients have their tumour removed, titanium clips are placed at the time of surgery to mark the tumour bed and improve radiotherapy accuracy. Reducing the risk of cardiac complications New techniques are also helping radiotherapy patients reduce the risk of cardiac complications because the heart — which sits immediately behind the left breast — may be clipped with beams of radiation during treatment. “Modern radiotherapy techniques now make this risk very small,” explains Dr Locke. “One big recent adva nce is a tech n ique ca l led ‘voluntar y breat h-hold’, where patients take a really big breath in to make their heart move backwards, down and away from their breast.”

This simple strategy is effective at lowering instances of radiationinduced heart disease. Dr Locke emphasises that all these changes are evidence-based and introduced after robust randomised t r i a l s. “ We’re on t he c u s p of further improving treatments and patient experience. For instance, hypofractionation delivers higher doses of radiotherapy in far fewer treatments,” she says. “This makes a huge difference to patients’ lives. I expect that in the future we’ll be able to offer those patients who need it even more effective radiotherapy in even fewer treatments.” WRITTEN BY: TONY GREENWAY

Sponsored by

DR IMOGEN LOCKE Consultant Clinical Oncologist at The Royal Marsden NHS Foundation Trust

Info box The Royal Marsden Private Care is due to expand its presence in London, with a diagnostic and treatment facility opening in autumn 2020 on Cavendish square, between Oxford Street and Harley St reet. The new outpatients centre will offer patients fast and direct access to world-leading ex per ts, in an easily accessible and reassuring environment. www.royalmarsden.nhs.uk/

cavendish

World-class cancer specialists Over 2,500 specialists working collectively every day to better the lives of cancer patients. The Royal Marsden Private Care Like no other.

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Promoting prostate health awareness

Could exercise beat advanced prostate cancer? M

“Having been born in “The Butts” in Warwick (the longbow training area for the Castle in medieval times), I couldn’t have been luckier or more proud to actually carry the Olympic Torch through the grounds of the Castle!!”

WRITTEN BY: GRAHAM FULFORD Co-Founder, Graham Fulford Charitable Trust

Losing two close friends to this awful disease, and realising we had no knowledge of it, encouraged us to raise awareness of prostate cancer so others might make it in time.

WRITTEN BY: DR MARK BUZZA Global Director of Biomedical Research, Movember

Regular workouts can help men with early prostate cancer live better, for longer but could it also help patients with advanced disease?

S

t ay i n g phy s ic a l l y ac t ive might be the last thing on yo u r m i n d w h e n yo u ’r e ex hau ste d f rom dea l i ng w it h cancer - but exercise make a huge d i f ference before, du r i ng a nd after treatment. Cont i nu i ng to be physica l ly active throughout treatment has been proven to help prevent a decline in cardiorespiratory and muscle fitness. It also helps patients cope with cancer-related fatigue, improves their overall wellbeing and reduces the likelihood of dying from the disease that claims the lives of 11,000 men in the UK every year.

New exercise guidelines for cancer patients L a st mont h (O c tob er 2 019), a thorough review of the available ev idence, conducted by an international group of 40 experts led by the University of British Columbia, resulted in the development of new guidelines for preventing, managing and recovering from cancer. T h e u p d at e d i nt e r n at i o n a l recommendations now advise that taking part in exercise helps improve survival after a diagnosis of breast, colon and/or prostate cancer. This is good news for patients as it gives us a real opportunity to continue integrating exercise medicine within cancer care.

We need better understanding of how exercise affects those with advanced cancer

10 HEALTHAWARENESS.CO.UK

Taking part in exercise helps improve survival after a diagnosis of breast, colon and/or prostate cancer. However, we still don’t yet know enough about the benefits of exercise for men with advanced disease. This is a gap in our knowledge and an important question that needs to be studied. That’s why Movember has initiated the INTERVAL GAP4 trial, the first randomised, controlled trial in the world, which is aiming to prove whether high-intensity aerobic exercise combined with resistance training could extend the lives of men with metastatic prostate cancer. Over 20 research teams from eight countries, including the UK, US, Canada, Australia and Germany, are working together to recruit 866 men to test whether exercise could be prescribed as a medicine alongside standard treatments such as chemotherapy, radiotherapy or hormone therapy. Half of the men who sign up are assigned to the active (or supervised exercise) arm, while the other half are put on a control arm. Every man participating in the study is given regular check-ups (alongside their normal treatment).

Trialing a two-year, tailored exercise plan aimed to delay prostate cancer progression

Men on the supervised exercise arm are given a detailed training plan – designed to increase their strength, fitness and flexibility. The plan is specifically tailored to them and their disease and they will follow it for two years. The programme includes two 75-minute sessions of mixed resistance and aerobic exercise and one 30-minute session of aerobic exercise each week for the duration of the trial. A 2016 pilot study led by Professor Rob Newton from Edith Cowan University in Western Australia, published in the medical journal the British Medical Journal Open, demonstrated that this type of exercise has the potential to be a powerful tool to delay the progression of advanced prostate cancer. It’s an ambitious project and there is a long way to go, but we hope it could lead to a revolution in the way we tackle advanced prostate cancer. The men who join GAP4 are not only benefitting from the exercise programmes but by tracking their progress, they are also helping us get a better understanding of how best to treat the disease and improve the lives of all men living with prostate cancer. Read more at healthawareness.co.uk

y wife, Sue, and I started a charity in 2004 following the, sadly too late, prostate cancer diagnosis of a close friend and a close relative. Both were in their late 50s and sadly neither of them survived. It was a shock to have two loved ones diagnosed virtually at the same time and, with no knowledge of this insidious disease, we decided to try to make a difference by launching an awareness campaign with the emphasis on early diagnosis.

PSA tests are the best tool in our armory right now In 2005, we had a major bre a k t h rou g h when we were introduced to consultant urologist, Mr David Baxter-Smith who, at our first meeting, when asked. ‘How do we help find prostate cancers?’ replied: ‘PSA testing. It’s far from perfect but there’s currently nothing else.’ Fourteen years later, with his help and working with groups including prostate cancer support groups, Lions Clubs, Rotarians, Masonic lodges and others, we’ve helped carry out over 140,000 tests on over 100,000 men from over 69,500 different postcodes around the UK. We’ve helped find 1,820 cancers on the results so far. We a r e f u l l y aw a r e of t he limitations of the PSA test, but until a more focused test is available, we feel we should make the most of it.

Alerting those most at risk with possible treatment options We operate a ‘green; amber and red’ alert system. The rule of thumb statistics show that, for every 100 tests we carry out, 90 will be green, four will be amber and six will be red. Of the reds, around one in four turns out to be prostate cancer. Those patients presenting red results will be sent a letter with information on the importance of

MRI scanning before biopsy. It will also include a summary of the three leading treatment options that our 1,820 cancer finds have revealed as most appropriate next steps: • ‘A c t i v e s u r v e i l l a n c e ’ i s considered most appropriate for non agg ressive cancer a nd has been apt for 21% of patients • 26% opt for surgery • and 33% elect for radiotherapy. We send a copy of the Space OAR leaflet to all these men on the basis that, for every 100 red letters, eight will end up having radiotherapy, and we feel they should be aware of the benefits of this breakthrough technology.

Companies are supporting employees by offering PSA tests We’re doing more and more in-house, corporate testing as employers become more and more aware of the importance of looking after their workers’ welfare and are happy to travel the length and breadth of the country with our Awareness and Testing Programme. We have a launch seminar on 28th November to introduce our new Online Registration and Result Retrieval System, which will enable us to carry out even more events and tests in 2020.

Info box For full details about the charity, how to hold an event and upcoming events in your area please visit us at

www.psatests.org.uk

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7 ways to cut down cancer 7 ways to cut down cancer 7 ways to cut down cancer Be smoke free Be smoke free

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Be safe in the sun

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Eat a high fibre diet Eat a high Eat a high fibre diet fibre diet Cut down on processed meat Cut down on Cut down on processed meat Be moreprocessed active meat

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Larger circles indicate more UK cancer cases

Circle size here is not relative to other infographics based on Brown et al 2018. Source: Brown et al, British Journal of Cancer, 2018

Larger circles indicatecases more UK cancer cases Larger circles indicate more UK cancer

here infographics is not relativebased to other infographics based on Brown et al 2018. Circle size here is not Circle relativesize to other on Brown et al 2018. Source: Brown al, British Journal of Cancer, 2018 cruk.org/prevention Source: Brown et al, British Journal ofet Cancer, 2018

Together we will beat cancer cruk.org/prevention cruk.org/prevention Together we will beat cancer Together we will beat cancer MEDIAPLANET

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Cancer becomes personal By 2040, there will be 27.5 million new cases of cancer each year. Innovation is and will be instrumental in tackling this epidemic and helping radically improve patient outcomes and quality of life. We at SOPHiA GENETICS are determined to do that by driving forward what we call Data-Driven Medicine. This is where each patient is supported with a tailored approach, from diagnosis to treatment. Let’s join forces. Learn more at sophiagenetics.com

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