C a n c e r W o r l d 2 5 Education & knowledge through people & facts J U L

Y Number 25, July-August 2008 - A U G U S T 2 0 0 8

MIke Richards

§ Mike Richards: the man with the plan § World Cancer Declaration puts cancer control on the global human rights agenda § Poor health literacy prompts warnings of an underclass § Careers in cancer: the next generation voices its frustration Contents

3 Editorial A question of human dignity

4 Cover Story Mike Richards: the man with the plan

14 Grand Round The hopes and frustrations of a career in cancer: the next generation speaks out Editor Kathy Redmond [email protected] 22 Drug Watch

Assistant Editor Personalised medicine: the dream and the reality Anna Wagstaff

Editorial Assistant 28 Masterpiece Corinne Hall A scientist without borders Editorial Board Franco Cavalli (chair), Alberto Costa Jacques Bernier, Vincent T. DeVita 36 Spotlight on... Lex Eggermont, Jan Foubert Lynn Faulds Wood , Mike Richards Tackling cancer in the Middle East: Euro-Arab School of Oncology Umberto Veronesi contributes a mix of international and local expertise Contributing Writers Ghassan Abou-Alfa, Marc Beishon Jim Boumelha, Noah Choi 40 Impact Factor Janet Fricker, Lia Halasz Peter McIntyre, Eileen O’Reilly Does prophylactic cranial irradiation reduce the incidence of Anna Wagstaff brain metastases in extensive small-cell lung cancer? Publishing Advisors Comparison of gemcitabine plus platinum analogue with Gillian Griffith, Fedele Gubitosi gemcitabine alone in advanced pancreatic cancer Website Liaison Chatrina Melcher Newsround

Art Editor Jason Harris 52 Patient Voice

Layout Designer Europe must tackle health illiteracy to avoid a health ‘underclass’ Max Fuller

Production 58 Systems & Services HarrisDPI www.harrisdpi.co.uk We’re back! How an alliance of patients and politicians put cancer

Printed by back on the EU agenda Arti Grafiche Amilcare Pizzi

Cover photograph Jason Harris

Published by European School of Oncology

Direttore responsabile Alberto Costa

Registrazione Tribunale di Roma Decreto n. 436 del 8.11.2004

All enquiries about Cancer World should be made to: ESO Editorial Office Via del Bollo 4 20123 Milan, Italy e-mail: [email protected] Fax: +39 02 8546 4545 All correspondence should be sent to the Editor at [email protected] Cancer World is published six times per year by the European School of Oncology with an average print run of 10,000 copies. It is distributed at major conferences, Copyright ©2008 European School of Oncology. mailed to subscribers and to European opinion leaders, and is available online at All rights reserved www.cancerworld.org

CANCER WORLD I JULY/AUGUST 2008 I 1 Editorial

A question of human dignity

§ Mary Robinson I GUEST EDITOR

ocial and economic progress over life-saving tools such as HPV vaccines avail - the course of the last century has able to those who need them most and to helped people in many countries ensure that robust health systems are in place Senjoy longer, healthier lives. Public health, by to support their delivery. and large, has improved and health inter - The World Cancer Declaration, which ventions are now available to prevent or treat will be launched at the UICC World Cancer most conditions, including cancer. Congress in Geneva this August, outlines Yet cancer continues to kill millions of the critical steps needed to build the basis for people worldwide every year and the death toll sustainable delivery of effective cancer pre - is projected to rise dramatically.A full 70% of vention, early detection, treatment and pal - these deaths occur in low- and middle- liative care worldwide. The Congress provides income countries. a critical forum for health professionals, pol - According to the WHO, up to one third of icy makers and advocates to galvanise the the cancer burden could be cured if detected global health community behind the goals of early and treated adequately, and another the Declaration. third could be reduced through cancer pre - These and other steps to advance global vention strategies aimed at reducing the expo - health are not just matters of moral concern: sure to cancer risk. These include changes they are issues of fundamental human rights. in tobacco use, immunisation against HPV Article 25 of the Universal Declaration of infection and control of occupational hazards. Human Rights declares that “everyone has Cervical cancer is just one example. the right to a standard of living adequate for Although we have the tools to prevent this ter - the health and well-being of himself and his rible disease, it affects an estimated 500,000 family, including medical care.” women each year and leads to more than As members of The Elders, we have 250,000 deaths – the vast majority in devel - highlighted the right to health as part of oping countries. Most women affected do not the Every Human Has Rights Campaign have access to local health systems or routine (www.everyhumanhasrights.org) to mark the gynaecological care, including regular screen - 60 th anniversary of the Universal Declaration. ing, which plays a critical role in preventing The message that health is a fundamen - cancer in industrialised countries. tal human right must be heard again Much more must be done to encourage today. We all have a role to play in moving the the international support necessary to make cancer control agenda forward.

Mary Robinson, former UN High Commissioner for Human Rights, is the President of Realizing Rights (www.realizingrights.org) and a member of The Elders – a group of public figures noted as elder statesmen, peace activists, and human rights advocates

CANCER WORLD I JULY/AUGUST 2008 I 3 Cover Story

Mike Richards: the man with the plan

§ Marc Beishon

“Congratulations, you are now in charge of sorting out England’s failing cancer services, what are your plans and can you start on Monday?” The job offer took Mike Richards by surprise but, mindful of the fickle nature of political support, he accepted the post, got straight down to work, and within six months he not only had a plan, but was ready to put it into action.

here are two ways of looking at the job of other countries in the UK, to which responsibility for a country’s cancer ‘czar’ – the person health has now been devolved). The NHS Cancer charged with masterminding a national Plan for England as drawn up in 2000 was, as cancer control plan. Many will see it as Richards says, a long overdue necessity. an impossible task, trying to keep every - “No country has a perfect system, but ours was far oTne from politicians to doctors and patient groups in behind many,” he says. “When I became national can - line with a programme that could never be compre - cer director I visited Sweden and talked to people in hensive and chasing targets that are constantly out of charge of service delivery – they told me we were reach, thanks to an ageing population, unhealthy beginning to do the right things but they’d started 20 lifestyles and lack of treatment progress, not to men - years earlier, with systems such as regional care net - tion continual changes in healthcare bureaucracy. works and service guidelines. The UK had great Others, however, will point to countries where a fragmentation in its cancer workforce and too few cancer plan and its leader have made clear progress people and facilities – we were not looking at cancer despite these odds, and on the international stage in the round, from prevention to screening, diagno - arguably the most prominent example is England and sis, treatment and care. It was a system failure.” its national cancer director, Mike Richards. The plan in 2000 set out to address these short - England stands out because, when it embarked comings. It has now been revised as a new reform on its cancer plan in 2000, it was the first large strategy, targeting in more sophisticated ways areas country in recent years to take this step. Denmark that are proving most problematic, such as early started its plan around the same time, but it was not diagnosis. After several years of spending a lot more until 2003, with the launch of the French cancer on cancer – although still less per head than Germany plan, that another large country followed suit. Eng - or France – the emphasis is shifting to effectiveness, land also stands out as a country that was in desper - and Richards is now looking to establish England’s ate need of playing ‘catch up’ with comparable cancer care among the world’s best. countries in the West (and this also applied to the For his own part, Richards – who was a professor

4 I CANCER WORLD I JULY/AUGUST 2008 Cover Story S I R R A H N O S A J

CANCER WORLD I JULY/AUGUST 2008 I 5 Cover Story

of palliative medicine in his last clinical post – does “I come from a medical family – my father was a GP, not preside over an expensive bricks-and-mortar and both my sister and brother had gone into medi - institute to direct the strategy. He has kept his office cine – but I hadn’t seriously considered it myself until at St Thomas’ hospital, London, with a view over the I switched from a natural science degree at the end River Thames to the Houses of Parliament, and has of my first year at university. I found it combined sci - a small team to call on. Networks, and networking, ence with humanity and I’ve never regretted making he feels, are far more effective than central diktat. the change,” he says. A snapshot of just a few days in Richards’ diary Richards did the usual training in general medi - reveals just how varied his own networking is – and cine, and found his way into medical oncology. “It provides an insight into what a cancer czar does. wasn’t any one factor – but an influence was meeting “I had meetings and workshops on England’s End of Gordon Hamilton-Fairley when I was a student at Life Care Programme [which Richards leads]; gave St Bartholomew’s [‘Barts’] in London. He was a very a briefing to England’s health minister preparing for charismatic leader in this new field, but was tragically a European summit; made a presentation on the eco - the victim of an IRA bomb. I also got involved with nomics of care at the Berlin breast cancer conference; one of the first randomised controlled trials for chaired a meeting with other national clinical direc - chemotherapy, in small-cell lung cancer, while work - tors; attended a meeting on funding hospices; met the ing in Nottingham.” chief executive of Cancer Research UK on initiatives At Barts, a specialist centre for haemo-oncology, for early diagnosis; attended a session on ‘e-learning’ he gained exposure to lymphoma and leukaemia, and for oncologists; and attended meetings on initiatives saw the potential of one of the first MRI machines in such as the UK’s National Cancer Research Institute, detecting lymphomas. “That’s given me insight into radiotherapy standards, laparoscopic surgery and how you evaluate diagnostic technologies, which is multidisciplinary teamworking.” not an easy area,” he notes. All this activity points to another key factor in run - He then moved to Guy’s hospital in London to ning a national cancer programme – leadership. become a breast cancer specialist, although he’d While a string of health ministers – and now one had little experience with the disease. “I’ve demon - Prime Minister – have come and gone under strated throughout my career that I can take jobs for Richards’ tenure, he has been in post for all eight years which I’m not qualified,” he says, adding more seri - of the initial plan, and has every intention of seeing ously that oncologists should be prepared to be through the latest reform strategy during the next five adventurous in the way their careers evolve. Guy’s years. Finding a director for a national plan is no easy was (and is, with its merger with St Thomas’ hospi - task for a government – there are very few senior cli - tal) one of the UK’s leading teaching hospitals, and nicians in any country who possess the necessary Richards was able to practise high-quality breast managerial and diplomatic skills, and who are pre - cancer care with some of the latest equipment and pared to step away from successful jobs in front-line multidisciplinary working. But in the early 1990s he oncology. But an oncology background is surely a pre - took a seminal phone call from an oncologist in a hos - requisite for gaining the confidence of a diverse and pital outside London. complex healthcare workforce. “This colleague was based in a city just 50 miles Richards thoroughly enjoyed his time as an oncol - from London, and he asked my opinion about ogist and researcher and had never envisaged becom - whether a 32-year-old woman with breast cancer ing a manager. “Fifteen years ago I wouldn’t have should receive adjuvant chemotherapy. I asked three believed anyone who told me I’d leave my clinical questions. Has the cancer spread to the axillary work to take on a role like this. lymph nodes? Answer: ‘The surgeons here do not “Oncologists should be prepared to be adventurous in the way their careers evolve”

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remove lymph nodes.’ Second – what grade is it? ‘The pathologists here don’t measure the grade.’ Finally, I asked how large the tumour was – and was told it was not recorded in that case. I was horrified by this stan - dard of care, and thought then I could either sit in my ivory tower and practise on relatively few patients or try to do things on a wider scale.” Working with colleagues in his regional cancer registry he found that this was not an isolated exam - ple, and there were wide variations in care. “That led me to work with the British Breast Group, which comprised researchers from a variety of backgrounds, where we wanted to produce guidance on breast can - cer services. We were told it would be impossible to get consensus, but in six months we wrote a docu - ment on multidisciplinary teamworking in breast cancer, and that led to national guidance for all sorts of cancers. It was a very influential programme – these were not clinical treatment guidelines, but how services should be organised, as it became apparent that the problem in the UK was more about the system than anything else.” included patients diagnosed from 1980 to 1984, Celebrating success. Along with underinvestment in the workforce and came out in 1989, and showed the UK well down the Earlier this year facilities, Richards says there was far too much frag - ranking for survival. The subsequent Eurocare-2 Richards marked mentation among the tiers of the health service – and 3 studies showed, he says, “that although out - 20 years of the primary, secondary and tertiary – and also among dis - comes were improving in the UK, the country was not NHS breast ciplines within the acute sector. “People working in closing the gap with others.” While it is easy to dismiss screening programme oncology were of high quality, but many were not some of the findings – there is for example incomplete together with the looking sufficiently broadly at the care pathway.” cancer registration in Germany and regional bias in Health Minister Some other countries still suffer from very simi - Italy – Richards says it became quite clear that data Alan Johnson lar fragmentation and underinvestment in their can - from Norway and Sweden, which have complete reg - (wielding the knife), cer services, so an important question is how such a istration, were indicative of a higher quality cancer Maureen Lubert situation arises and is allowed to continue. Losing sev - control system. from the charity eral cancer champions, such as Hamilton-Fairley, and Eurocare-3 covered survival up to 1999, the year Breakthrough Breast in the early 1990s, the pioneering medical oncologist before the NHS Cancer Plan, but Eurocare-4, pub - Cancer and Jeremy Timothy McElwain, certainly did not help, reckons lished last year, covered the early years of the plan and Hughes MP from the Richards, but generally cancer did not have a high led to press reports that it is failing, as the UK figures Parliamentary Group enough profile in the UK – in the media, among the were still not good. Richards notes, however, in an arti - on Breast Cancer. public or in medicine. “And there was a fatalistic atti - cle on the Eurocare approach, that the time lag from The cancer reform tude, such that when I was a junior doctor an eminent diagnosis to analysis (from five to seven years) needs strategy will extend gastroenterologist told me he couldn’t understand to be narrowed, and better information, such as on the programme to why I wanted to be an oncologist. Equally, as a coun - staging and symptom duration, needs to be added women aged 47–73 try, we were slow to believe we had fallen behind in (see Lancet Oncology , online 21August 2007). He is care. We had a passionate belief in the NHS and it confident that England’s cancer mortality and survival was hard to think our outcomes were worse than rates will show a closing of the gap with other nations. comparable countries.” Richards made another career switch that was to It was the Eurocare comparative studies of Euro - prove prescient, given his current leadership role in pean cancer registries that triggered a change in England’s End of Life Care Programme, becoming British thinking, says Richards. Eurocare-1, which professor of palliative medicine at Guy’s and

CANCER WORLD I JULY/AUGUST 2008 I 7 Cover Story

are your plans and can you start on Monday?’” This was the first salaried post of its type in gov - ernment – not an advisory position but a full-time pro - gramme leader. “I then had a meeting with Tony Blair and put forward the idea of a national plan. He asked, ‘Is cancer in this country as bad as made out, why is it so, what can you do about it, how long will it take and what will it cost?’ The plan came out of that meeting – and it was clear to me that when you have political support you should act fast, and we pub - lished it six months later.” Richards worked mainly with a small, informal group of advisers from across the cancer spectrum, as it was clear what the main priorities should be, espe - cially on the treatment side. But he emphasises that a cancer control plan should be a very broad pro - gramme, from prevention to screening, treatment and indeed end of life care, informed by existing evidence and new research as needed. “But there won’t always be controlled trials that show you how services should be – I cannot envisage doing an RCT on multidisci - plinary team working, for example, as it is unthinkable we’d randomise patients to be managed by profes - sionals who don’t work closely together. Sometimes you have to work with commonsense and consensus.” Indeed, he says the single biggest change so far has been in creating multidisciplinary teams (more than 1,500 are in place), aligned with reconfiguring services so that complex procedures are carried out in larger centres where there is evidence that this improves outcomes. “We’ve moved a lot further here than some countries have been able to – such as for oesophageal cancer, where you should be dealing with S I populations of a million or more, and pancreatic R R

A cancers, for 2 million and over. And now the vast H

N majority of men who undergo a prostatectomy are O S A J treated at centres with at least 40 procedures. Each year progress is in the right direction.” He adds that St Thomas’. “It made a big impact on me,” he says.At units that do not measure up have been closed. For the same time, he was working with the Department example the number of hospitals carrying out major of Health on reducing waiting times and improving oesophageal/gastric procedures has halved from 160 standards in the cancer service, but it came as a big to about 80. But he is not an advocate of migrating too surprise when he was selected as the national cancer far in the direction of a few comprehensive cancer director in 1999. “The Prime Minister, Tony Blair, had centres – England now has regional networks and he held a cancer summit earlier that year, where about is keen to see as much appropriate care as possible 25 people including myself set out the problems. located close to home, with involvement from primary Later, I was asked to attend what I thought was an care and district hospitals, and increasing use of interview with the health minister – but she said, tools such as videoconferencing. ‘It is great that you are going to do the job. What The earlier service documents for cancer types

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that Richards helped to draw up have now evolved access to new drugs such as Herceptin, often pre - into guidance produced by England’s National Insti - sented using highly emotive stories about young tute for Health and Clinical Excellence (NICE). cancer sufferers. “We have acknowledged that the “Each report says what the shape of services should interval between a drug being licensed by the Euro - be and who is needed in a multidisciplinary team for pean MedicinesAgency and approval by NICE is too the relevant cancer type. We also have a system of long,” he says, adding that there are moves to speed peer review in place to assess whether services meet up appraisal and to monitor the variation of provision the recommended stance.” For the most common around the country. It is not a uniquely British prob - cancers and also for supporting services such as lem though. “Variations in the use of drugs and sur - radiotherapy and pathology, Richards says more than gical procedures feature in most countries,” he notes. 2,000 reviews by outside colleagues have been con - Waiting times from referral by a primary care doc - ducted so far – these are mainly appraisals of proce - tor (GP) to being seen by a specialist are now much dures but may include sitting in on team meetings. shorter – there is a two-week target set by govern - A report on the peer review findings is in prepa - ment. But there can still be lengthy delays in access - ration, and should also be of interest to international ing treatment such as radiotherapy. Late presentation colleagues. “We have identified much good practice, by patients and late onward referral by GPs have but there are still places where the workforce is not remained tough nuts to crack, and are major planks sufficient to hold, say, weekly multidisciplinary meet - of the reform strategy. However, a cancer czar can eas - ings. They may be missing certain specialists such as ily find himself at the centre of a dispute which is not pathologists and, in some cases, nurse specialists, who of his making. A recent front page newspaper story we think are a very important part of the team. suggested that Richards had issued a ‘warning’ to GPs “Administrative support is also a challenge. We about ‘botched diagnoses’. “I was scurrilously mis - have spent ten years building up these teams – now represented,” says Richards. “I did say it is hard for we need to make sure they work effectively.” GPs who see only about eight new cancer cases a year Prevention has made headway – smoking rates to distinguish these from the hundreds of people they among adults have now dropped to 22%, and should see with similar symptoms. I had not issued a ‘warn - fall further following the recent smoking ban in pub - ing’, nor had I mentioned ‘botched diagnoses’. In Eng - lic places in England. Richards reports “major suc - land we ask GPs to be gatekeepers and we need to cess” in screening, with women aged 50–70 now equip them with decision-making aids and better screened for breast cancer with two-view mammog - access to diagnostic tests like ultrasound. What we raphy, and colorectal cancer screening being rolled out don’t need are more guidelines – GPs are already to people in their 60s. Limiting factors, such as the flooded with these.” availability of high-quality endoscopy services, are An important point he stresses is that, while being mitigated by expanding the range of practi - many of the issues facing England are common to tioners who can carry them out – including nurse spe - other countries, what needs to be done has to fit with cialists – and insisting that units must improve the existing healthcare system. While he can see quality and cut waiting times to be part of the national some changes, which might include increasing screening programme. recourse to private medical facilities, the NHS and its Probably the parts of the 2000 plan that have been primary/acute system is not likely to change radically. – and continue to be – most controversial, certainly “The NHS has changed over the past eight years. in the public eye, concern waiting times and drug In the year 2000 plans were all about expansion – availability. Richards regularly appears in newspaper now it’s about driving change through better infor - items on subjects including the wide variability of mation and commissioning, and yes, we can now look “We have spent ten years building up these teams – now we need to make sure they work effectively”

CANCER WORLD I JULY/AUGUST 2008 I 9 Cover Story

increasing the move towards carrying out more com - plex procedures in major centres, while doing more ambulatory care closer to home. “We need to free up resources: we spend a lot more on inpatient services for cancer than they do in the US,” says Richards. Collecting and applying better information is also a major plank of the strategy. “We already have com - prehensive cancer registration and extensive infor - mation on patients attending NHS hospitals in England, but we are not making the best use of this.” A national cancer intelligence network is now being established to provide comparative data on cancer activity and outcomes. “My aim is to have the best cancer information system of any large-population country by 2012.” Critical Until recently, Richards was also the chair of the coverage. National Cancer Research Institute (NCRI), the vir - Richards tual coordination body for research centres and has had to funding bodies in the UK. The cancer plan has trig - learn to deal gered much more research, says Richards – and cer - with the British tainly the various networking initiatives now running press, where are among the more visible success stories on the stories on international stage.Among the achievements are the the NHS tend to National Cancer Research Network, designed to be driven by a to the indepen- boost clinical trial rates in NHS hospitals (the enrol - political agenda dent sector if we want.” ment rate has now reached 12%). A recent initiative The cancer reform strategy has been to establish 19 experimental cancer med - includes actions to diagnose cancer ear - icine centres to fast-track phase I/II trials. lier through extensions to screening and helping The NCRI, adds Richards, also maintains the primary care, and it also has a new equality initiative same database structure of ongoing research as to tackle disparities among populations that have the US and Canada. “I would very much like to worse incidence, access to services and outcomes. make this a Europe-wide initiative, so we can bet - “We need to push relentlessly on the smoking agenda ter identify gaps in research.” Analysis of the – should cigarette displays now be banned in shops, database showed low levels of funding on research for example – and develop community awareness. into prevention and into supportive and palliative We have a number of pilot programmes running in care. As a result, new initiatives have been estab - deprived areas that are trying to inform older people lished in both areas. about the major cancers – it is partly the media’s fault Richards’ involvement with England’s End of that many think that cancer is a disease of younger Life Care Programme goes beyond cancer to all people and not primarily of people in their 60s, 70s illnesses – as he says, the majority of the 500,000 and 80s. The media always tend to focus on younger deaths in England each year are from a chronic cancer patients.” condition. But, as with cancer care a decade ago, end Other elements of the new strategy include of life experience can vary greatly in quality, and “It is partly the media’s fault that many think that cancer is a disease of younger people”

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Richards would like to see much more awareness, and even anger, about poor end of life care

Richards would like to see much more awareness – and even anger – about poor care to help drive up quality for a topic that tends not to be talked about. “Doctors need to be trained to initiate discussion with people about their preferences regarding end of life care – much of the problem starts at the begin - ning of the end of life pathway.” For palliative care, he notes the huge range of professionals who are involved in helping people towards the end of their lives – but relatively few who are specifically trained in the discipline. “We need to skill up the wider professional community and improve coordination, for example, so that people do not end up in hospital unnecessarily.” Survivorship care, as more and more people live with after-effects of treatment, also now needs greater attention, he adds. Richards recognises that there will be continu - ing controversies, adding to the string of problems that have already landed on his desk, such as short - comings in radiotherapy and drug availability. On the latter, the NHS is now in the bizarre but under - I T standable situation of not allowing patients to pay A R for their own drugs and have them administered by O M A the NHS, as this would promote inequalities. Such N N I I

‘co-payments’ are commonplace in many Euro - G I U pean countries. L One of Richards’ biggest critics – and simulta - neously one of his friends – is probably the best There is little disagreement – apart from the odd Walking a tightrope. known British oncologist, Karol Sikora, who is agi - map-reading dispute – with Sikora when they are out Richards spoke of the tating for much more and faster reform, such as a hill walking, Richards’ great passion outside work. need to maximise the network of dedicated privately-run clinics, to drive “My aim is to climb all the Munros in Scotland – value cancer patients efficiency, and wider drug availability. “There are ten these are mountains over 3,000 feet (914 metres) – get from a limited cancer drugs you can get in Calais that you can’t get there are 284, and I have done 232 so far.” health budget at a in Canterbury,” he comments. But Sikora recognises It’s an apt analogy with England’s cancer con - panel debating the the tightrope that Richards walks, despite labelling trol plan – opinions vary but no one can now case for rationing him a ‘political servant’. As Richards says: “I can’t deny that a concerted ascent of the cancer moun - expensive drugs that keep everyone happy – the way I work is to keep tain has been made. “My ambition now is for was organised to what’s right for the patient clearly in mind in the way England to be among the best in Europe and the mark the 25th I respond, and that does make me unpopular with world in cancer, and recognised as such, and also anniversary of the some groups.” No doubt sometimes the politicians to be a leader in end of life care. But of course it European School of feel he is the patients’ – or the oncologists’ – servant. is still a big challenge.” Oncology last year

CANCER WORLD I JULY/AUGUST 2008 I 11 Grand Round

The hopes and frustrations of a career in cancer The next generation speaks out

§ Anna Wagstaff

Young oncologists want the chance to develop their skills, reach their full potential and give of their best. But a Cancer World survey shows many are frustrated by too heavy clinical workloads, too few chances to lead research and get published, and too little recognition for their clinical skills. Are potential leaders of oncology in Europe having their careers derailed?

or young medics setting out among them is the weight of the clinical ical. But even hospitals with a good gen - on their careers, oncology workload – rated the first or second most eral reputation for training can turn out offers almost unparalleled important barrier in every region of to be poor when it comes to oncology. richness. You can be part of Europe. In western and southern Europe, There were comments about very the march of science, work - this is coupled with a strong sense that the good practice: “I said to [my supervisor] iFng with lab and clinical researchers on an quantity and quality of clinical work that I wanted to do something in the international stage. You can build up counts for little when deciding who lab, and he found me funds to do it. I said expertise in particular cancers, working in should be promoted. In central and east - I was keen to gain some more experience a team to apply it to each new patient. You ern European (CEE) countries, pay and in breast, and he found me somewhere to can make a world of difference to the lives lack of job openings and training posts are train in breast. I said I had just heard of patients and their families. seen as major barriers. about the Flims course [on methods in Science, medicine and humanity: To throw some light on these and clinical research] and asked, ‘Would you oncology offers all three. In an ideal world, other issues, Cancer World talked to a help me to go there?’, and yes he did.” medical students choosing oncology will number of oncologists in their 30s or And comments about very bad prac - taste all these aspects, find out where early 40s, who have completed their basic tice: “They use their students as menial their talents lie, and develop their careers training and are building their careers. workers, getting them to write down accordingly. Such a world would also be patients’ clinical records, prepare their ideal for patients and for medical progress. QUALITY OF TEACHING charts and fetch the films from radiology. But how far does it match reality? One interesting finding is the variety of But they never give them the chance to A survey conducted by Cancer World experiences. In a profession that relies discuss that film for 15 minutes with a has revealed a variety of barriers to devel - heavily on ‘learning by doing’, the qual - senior specialist in radiology.” oping a career as a cancer specialist. Top ity of the teaching and mentoring is crit - Frustration at being denied oppor -

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tunities to assume greater responsibility RESEARCH BARRIERS seems widespread. One interviewee The Cancer World survey revealed that described how even good people can get many young oncologists are finding it trapped. “One of my colleagues, a bril - hard to build up experience in liant radiotherapist, suffered for almost research – with few opportu - 10 years under a boss who wouldn’t nities to do lab work, design let him move and didn’t give him free - protocols or lead trials, and dom to develop.” many obstacles to getting The problem seems to get worse published. This is a parti- as you reach the end cular problem in countries of your residency or institutions with a low and try to break into commitment to medical the higher ranks. research (for a comparison “Those who are still of per capita spending on in training have many cancer research across more opportunities Europe, see figure 6 of the than a few years ago. Second Cancer Research The problem is when Funding Survey , ECRM you are in the middle,” 2007, www.ecrmforum.org). said one senior A survey respondent oncologist. “People from Austria called for ‘our who have been in own national cancer institute’. a backstage posi - Comments from Spain and tion for a long Turkey called for ‘collab - time and who orative research groups’; have learned from Ukraine, ‘good how to do labs with high-tech it should facilities’; and from be given Bulgaria, the Czech Re- the opportu - public, Italy, Turkey nity to lead and Romania, ‘more projects.” research grants’, ‘more Often a head of sponsors to run trials’, department seems to pro - and ‘greater emphasis K U tect their own patch. on research and giv - . O C .

“Maybe they know we are ing it time’. T R A S

the generation who are But good transla - I N going to replace them. tional research requires A G R O There are very few people who say: ‘I am more than just the right . W going to prepare things for when I leave.’ bility for training lies with each of the 52 facilities. A strong working relationship W W ,

I guess it’s only human.” länder , there is no national accreditation between lab scientists and clinicians is N E L

Another commented, “There are of training programmes for any specialty. essential, yet this seems more of an ideal E E places where you feel a ceiling, not even Some of the German respondents to the than a reality. “The people in the lab are not D N A a glass ceiling, just one centimetre above Cancer World survey are calling for a really interested in care and the people in V D E your head and you can’t move. Actually national curriculum – consistently taught the clinic don’t have interaction with peo - R F : they are trying to push the ceiling down.” and rigorously evaluated. ple in the lab. It is so difficult that in the N O I T

Big differences in the quality and Moves towards devolving healthcare end people do just straightforward clinical A R T evaluation of training programmes is also to the regions in Spain are prompting research – not the translational stuff.” S U L L an issue. In Germany, where responsi - similar calls. Clinical research is itself highly I

CANCER WORLD I JULY/AUGUST 2008 I 15 Grand Round

demanding. It takes money, time and an in these forms. It’s desperate – it’s a Bordet. “I published an original article, immense amount of administrative and humungous amount of work.” but it was only theAmerican journals who clerical work. Unless a centre has well- Even when an oncologist overcomes were interested. Europe is extremely prej - oiled procedures, clinical trial nurses, these barriers, it is difficult to get pub - udiced. They feel southern Europe is the admin staff, software and other back-up, lished in a prestigious journal. Braga com - end of the world. I always tell my fellows the burden on the trial leaders can be ments, “My institution has not broken to send papers toAmerican meetings and enormous. Sofia Braga, a young Por - into that kind of group, where your name journals, because they respect us.” tuguese oncologist, worked for a year at the is known. We’re still in a place where Jules Bordet in Brussels and is now back in some of us have had international expe - THE CHANCE TO TRAVEL Lisbon, at one of Portugal’s three large rience and we’d love to publish more, Travel is one answer – it is notable how oncology institutes, fighting for the chance but it’s very hard. We don’t have a Baselga, many specialists who make the cover of to lead a trial of sunitinib as a neoadjuvant a Piccart or an Armand.” Cancer World mention an opportunity in breast cancer. She contrasts the two She feels that many European journals to spend time in a different country as key settings: “They get protected time. And are biased against places like Portugal, to their subsequent careers. Many pro - they don’t have to fill in CRFs [case even though her centre treats more breast fessional and educational organisations report forms]. I spend my day filling cancers than, for instance, the Jules offer fellowships where people can get experience in research in different envi - WANT CAREER – MUST TRAVEL ronments (see box). However, demand is always greater ESSO, the society for surgical oncology in research fellowship offers oncologists with than supply, and while some supervisors Europe (www.esso-surgeonline.org), offers some experience in research the chance to encourage their trainees to seek experi - fellowships to give young surgeons the work in a lab. ence abroad, others resent losing an extra chance to expand their experience and learn ESMO recently introduced a ‘teach the pair of hands. Language is a barrier to new techniques. They also support surgeons teacher’ fellowship, which supports a group travel from countries which don’t have a who want to attend the Flims course on meth - of young oncologists from one centre to travel tradition of English as a second language. ods in clinical research. to a host institution for six weeks to learn dif - It is also harder to move when you have a ESTRO, the society for radiation oncologists ferent ways of organising clinical work and young family, or a partner tied to a job. (www.estro.be), offers grants and fellowships research – the aim is to maintain those links Women are at a particular disadvantage for courses, and advertises other fellowship once the group has returned, and support here (indeed, Braga cut short her term at and grant opportunities for radiotherapists on them in sharing what they learned. the Bordet and returned to Portugal its website. ESO, the European School of Oncology because of childcare problems). ESMO, the society for medical oncology (www.eso.net) offers, in addition to its own ESMO (the European Society for (www.esmo.org), recently beefed up its fel - courses, senior scholarships for young oncol - Medical Oncology) now offers research lowship opportunities. Young oncologists can ogists to visit specialist centres for three fellowships that can be carried out at the apply for a ‘taster visit’ to a translational months to a year for practical training in a vari - fellow’s own institution of origin, because research unit to see how this research is ety of specialties. of the difficulty some people find in trav - organised. A one-year clinically oriented fel - Other bodies offering fellowships include the elling. Martine Piccart, head of the med - lowship offers young oncologists an oppor - UICC (www.uicc.org), the European Organi - ical oncology department at the Jules tunity to visit an institution, participate in sation for Research and Treatment of Cancer Bordet institute in Brussels, who sits on multidisciplinary rounds, and see inpatients (www.eortc.be) and many major cancer cen - ESMO’s fellowships and awards commit - and outpatients. A two-year translational tres and charities in Europe and the US. tee says, “That’s good I think, but this model should not be favoured too much. I really believe that the most productive “We’d love to publish more, but it’s very hard. We don’t have a Baselga, a Piccart or an Armand”

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“If it doesn’t change, good people won’t be recognised as leaders, where they can influence what is going on” experience for these young people is to go welcome – increase in clinical posts, many respondents to the Cancer World elsewhere for a certain period.” there was no accompanying agenda to survey asked for just such training path - Romanian-born Razvan Popescu, who promote research, despite the excellent ways in their own countries. However, is now based in Switzerland and also sits potential offered by these new centres. there seems to be a feeling among young on the ESMO awards committee, has led Martine Piccart mentions the UK as French and British oncologists that this efforts to promote opportunities for young a positive example, where a national ini - system forces them to choose between oncologists from CEE countries to visit tiative to promote involvement in clinical being a clinician or an academic very early, other institutions to gain experience in trials in 2001 helped boost cancer patient making it harder to change direction as research and different models of clinical inclusion to 12% and opened up new their careers develop. practice. But he says it is also important opportunities for young oncologists. The Lack of opportunity for continuing to focus on what happens when (and if) National Cancer Research Network medical education is also heavily flagged they return. (www.ncrn.org.uk) is a collaborative effort up in the Cancer World survey. Though all Popescu would like to see between clinicians, the Department of areas of oncology are heading rapidly greater support for the Health and funding bodies – both state towards subspecialisation, there are few work of organisations and charitable – sustained by a significant opportunities to attend high-quality like CECOG, the Cen - number of ‘clinician researcher’ posts dis - courses. It is this gap, above all, that the tral and East European tributed across the UK’s cancer hospitals. European School of Oncology has sought Oncology Group, which In France, the Nat- to fill. It offers a one-week full-immer - are beginning to expand ional Cancer Plan sion masterclass for oncologists in their the opportunities for offers a further early 30s to give them a good overview of young oncologists to positive example. the field and help them decide which sub - design and conduct clin - The Plan pro - specialism to follow. Courses are free, and ical trials. He stresses the vided significant students continue to receive mentoring value such ‘home- funding for research, from faculty members for several years; grown’ trials could introduced a regional network however, only 50 –60 places are available have for patient of seven ‘cancero-poles’ (net - each year. There is also a pressing need for care, given that works) to coordinate and pro - continuing medical education courses in research into the mote research, and provided a oncology subspecialties. Currently, ESO is best allocation of back-up team to assist hospi - almost the sole non-industry provider, resources and optimising treatments that tals in building their clinical research capac - offering short courses in a variety of lan - are both good and affordable may be more ity. These measures undoubtedly opened guages, also free of charge. relevant than some of the research led by new opportunities for young oncologists, the west. though there are growing calls for the ACADEMIC -CLINICAL TENSION Lack of support for medical research decentralisation of research funding – cur - The uneasy relationship between aca - is not just a feature of the less wealthy rently concentrated in the hands of the demic and clinical structures seems a countries of central and eastern Europe. French National Cancer Institute INCa. major barrier. In France the best treat - Miguel Piris, leader of the Lymphoma Both the UK and France have specific ment and research in solid tumours is Group at the prestigious CNIO in training pathways for ‘academic clinicians’, done in 20 cancer centres outside the Madrid, complains that Spain missed a which integrate research into the resi - university hospital system. But a young great opportunity during recent heavy dency programme. This decreases the ele - doctor aiming for the prize position of investment in state-of-the-art hospitals. ment of luck about who gets opportunities ‘professor’ has to build a career in one of Though there was a significant – and to develop their research capacity. Indeed, the university hospitals. “You need to

CANCER WORLD I JULY/AUGUST 2008 I 17 Grand Round

“When they evaluate you for promotion, what counts is research and publication – not patient care” clone yourself,” said one young oncologist, stay at the university, often going from performance-based incentives and penal - “It can be very hard to know how to one short-term contract to the next, hop - ties. Funding for both hospitals and uni - organise your career.” ing to be chosen as successor to the incum - versities is increasingly based on evaluation The situation in Italy is not dissimilar. bent professor. and competition. Riccardo Vigneri, who has sat on Italy’s The system is unfair and deeply The plus side is that it forces poor national CME accreditation committee for unpopular, as many of the Italian respon - institutions to raise their game, and the past 10 years, says that many university dents to the Cancer World survey indi - reduces the abuse of personal power and hospitals are so poor at treating cancer cated. Vigneri says, “If it doesn’t change, lack of accountability in ‘Mandarin’ type that they don’t have enough patients to be good people won’t be recognised as lead - systems, by introducing transparent and able to teach, and have to farm students ers, they won’t get into positions of power objective measures of quality and merit. out to other hospitals for their clinical where they can influence what is going on Some people, however, think the compe - training. There they tend to be taught by around them.” tition has gone a bit too far. Michael Bau - the head or assistant head of oncology, The tension between the clinical and mann, professor of radiation oncology and who is not trained to teach and gets noth - academic sides, common to all medical head of the Cancer Centre at the Carl ing back for teaching. “They often use the fields, is exacerbated by the way oncology Gustav Carus University Hospital in Dres - trainee oncologists as menial workers. If is often fragmented across departments. den, comments, “Sometimes you would they do research, it is second class, doing This is a particular problem for cancer simply love some time off from writing protocols directed by the industry. Their surgeons, who not only have to split their grant applications and doing research – at critical faculties are not being engaged to training across a number of units – neu - the moment it is too competitive and too really understand what is going on.” rology, gastro-intestinal, pneumonology – little money.” He would like to see basic Italy has some excellent cancer centres but also have to compete with non-cancer personnel and lab resources guaranteed, which offer superb training opportunities surgeons for senior departmental posts. with additional grant money available on a for the minority of students who are lucky Financial pressures are now prompting competitive basis, more along the lines enough to be recruited. But a doctor who many governments to demand greater operating in the UK. “A good mixture of wants to build an academic career must value for money, and they are introducing the two would be perfect.At the moment, at least in the poorer places, you have to TOP BARRIERS TO CAREERS IN ONCOLOGY ACROSS EUROPE really fight for grants or you have nothing.”

DEVALUING CLINICAL WORK This heavy emphasis on competition is a growing trend across Europe, and seems to be adding a new dysfunctional twist to the relation between academic and medical worlds. Being an excellent doctor, who keeps abreast of developments, spends time with patients, works well in a multi - Respondents were asked to rate the top dents from each region who identified each disciplinary team and enters patients into three barriers to progressing their careers out barrier among their top three. clinical trials may no longer be enough. of a possible 10 options. The chart shows the Source: Cancer World survey. For further This is one of the key messages of the top five barriers, with the proportion of respon - details see www.cancerworld.org/magazine Cancer World survey, in which the second most mentioned barrier to an oncology career was the lack of value attributed to

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clinical work when deciding on promotion. earch, or 20/80 clinical/research. Once Since the number one issue is that the clin - their profile is agreed, we evaluate them ical workload leaves no time for research, yearly in accordance with that profile, these two barriers create a vicious spiral. because you won’t expect someone fully Fatima Cardoso is a senior oncologist involved in the clinic to publish three at the Jules Bordet institute in Brussels. papers a year, but you will expect that She has always enjoyed being involved in from someone doing research 80%.” research, and used to coordinate the trans - much lighter, There is a limit, however, to what lational research unit at the Bordet. But the pay is better, and heads of departments can do in the she ended up pulling out of the latter role clinical work is not under - absence of a joined up approach to because she feels very committed to car - valued. “We have lost three sen - healthcare and medical research. Pic - ing for her patients and was finding it ior oncologists in the last two years,” says cart deplores the short-sighted lack of impossible to do both. Cardoso, “The workload increases and interest shown by many European gov - She warns, however, that choosing to the workforce decreases.” ernments in supporting medical research, concentrate on patient care is a bad career Andrew Wardley, consultant medical and singles out the UK’s National Cancer move for any doctor, and for oncologists in oncologist at the Christie Hospital NHS Research Network, for praise. “This is particular. “When they evaluate you for Trust in Manchester, UK, agrees there is a something I consider very impressive.” promotion, what counts is your CV – problem with clinicians being treated as There is also a limit, she says, as to how research and publication – nothing to do second class within university hospitals. much departmental heads can do within a with patient care. I can understand that if “University hierarchies are only interested climate that increasingly devalues doc - you are applying for a research post, but if in science. In the past few years there has tors, and health structures that hugely you are applying for a position in a hospi - been a big culling of academic clinicians underestimate the skill and effort required tal, I don’t understand why people don’t from senior lecturer posts in top UK uni - in oncology. rate your value as a clinician.” versities. A lot of people feel the effort to “Governments need to re-evaluate how Fine ideas about ‘translational keep up their RAE [research rating based they support oncology clinics. When I see researchers’ in academic posts which allow on publications and grants] is not worth it, the time we need as oncologists to explain both clinical care and research work are and they’d rather stay with the NHS.” to patients their diagnosis, what is going to simply not reflected in reality, says Car - be done, the different treatment options, doso. “We are completely overstretched by NATIONAL POLICIES the side-effects of the treatment… You can our full-time work in the clinic. We are At the Jules Bordet institute, Martine Pic - easily spend one hour.And when you look going back to having to do the research in cart is very aware of the tensions between at what the hospital gets for that, it is our free time.” the clinical and research roles in an aca - peanuts.” The same applies to surgical Cardoso says her generation, now in demic hospital. “It is the responsibility of oncology: “These people often do opera - their early 40s, is suffering because the the director to recognise the value of very tions that last hours, and there is a ridicu - next generation are not choosing careers in good clinical work,” she says, “You cannot lously small amount of money in place for oncology. “They look at my generation, function with a team of doctors that do that kind of surgery.” and the way we work, and they tell us: ‘I only research, nor with a team that do no Even the battle to get recognition for don’t want to live the life you lead’. They research at all. To find this balance is not medical oncology as a specialty has not yet value their quality of life, so they don’t easy, and to avoid frustrations and jeal - been won in many countries. “That’s the choose this specialty.” ousies is quite a challenge.” first step and we are not there yet. How can At the same time, experienced and She tries to meet each oncologist indi - you be attracted to a profession that is committed oncologists are leaving – often vidually to agree on their mission. “They not even recognised, and where the things to the private sector where the workload is may be 100% clinical, 70/30 clinical/res- you do are permanently underpaid? “How can you be attracted to a profession where the things you do are permanently underpaid?”

CANCER WORLD I JULY/AUGUST 2008 I 19 Drug Watch

Personalised medicine: the dream and the reality

§ Marc Beishon

Recent years have seen a scramble to identify the genetic variance that predisposes or protects against certain cancers and the tumour gene signatures that could indicate which therapies will work and which won’t. A picture is now emerging of an infinitely complex field that is unlikely ever to live up to the high hopes of some scientists, but is certainly confounding the sceptics.

he lay public must be a bit con - and screening for the BRCA1 and 2 and yet he did develop melanoma). fused about the term ‘person - breast cancer genes. A recent tech - There has been a lot of hype about T alised medicine’, which has nique showing promise allows person - the value of both genetic variance and become one of the hottest health topics alised levels of chemotherapy dosing tumour profiling. Helping to bring us at present, judging by the sheer number for colorectal cancer patients based down to Earth is a professor who is of mentions it is getting in the mass on a blood test, rather than the ‘gold expert in research methodologies with media. On face value, it seems to imply standard’ of calculating drug dose by a special interest in genomics and can - that we have arrived at a promised land body surface area. cer, and is helping to navigate what is of individual treatment, certainly where It is genomics – and all the other becoming an exponentially complicated the genetic make-up of people and molecular sciences such as proteomics field. John Ioannidis, head of the disease is concerned. After all, the one – that are making the running in the department of hygiene and epidemi- concept that everyone knows is that personalised medicine debate. One ology at the University of Ioannina, we are all – bar identical twins – genet - person’s tumour is as different from Greece, made waves with a paper, ‘Why ically different from each other. But in another’s as a fingerprint or iris, so it is most published research findings are fact we are far away from applying many no wonder that cancer is a prime target false’ ( PLoS Medicine , 2005). He sug - different, individual treatment regi - for personalisation. There is now a mas - gested that the hottest scientific fields mens based on genetic characteristics. sive body of published papers – more – with many research teams involved – What personalised medicine cur - than 50,000 alone on molecular signa - are less likely to come up with true rently means in practice is treatments tures for cancer, for example. findings, and there is ‘ping pong’ or procedures that apply to groups of Interest and publications are also between extreme positive and negative people, although those groups could be growing fast in complex genetic variance results – and no topic illustrates this quite small parts of the population. In that may confer risk (or protection) – better than molecular genetics. general medicine, a transfusion of a hardly surprising as the human genome certain blood type is a ‘personalised’ has now been sequenced. Luminaries MARKERS OF RISK approach. In cancer there are many such as Craig Venter and James Watson Bearing this ‘reality check’ in mind, that can be mentioned, such as the have had their own DNA analysed Ioannidis is by no means pessimistic Herceptin (trastuzumab) monoclonal (in Venter’s case this showed he had about progress, and has an overview of antibody for Her2-positive tumours no known indication for skin cancer – where we currently are in both genetic

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variance and tumour profiling. “For genetic variance that confers risk or protects people from cancer, we have now seen identifiable progress for the first time in long while,” he says. “Until recently, we had only found syndromes with a high penetrance – meaning there are few genetic factors that could con - tribute an enormous level of risk, but were very uncommon – but they do not explain why most people get can - cer.” Well-known syndromes include hereditary non-polyposis colorectal cancer, Li-Fraumeni syndrome, the BRCA1 and BRCA2 genes and so on. Now, he adds, there are more rep- roducible findings about genetic variance carried by 10%–30% of people that increase or decrease risk of spe - cific cancers. “We have had most luck with breast and prostate cancer, and found half a dozen common variants, each of which increase or decrease the relative risk of getting these cancers by about a fifth, e.g. from 5% to 6% or 4% in terms of absolute life-time risk.” The variants, he says, are single nucleotide polymorphisms (SNPs, also known as ‘snips’). “Someone has, say, an A instead of a T in a sequence – but we don’t know whether these are the real culprits and are directly increasing risk. They could be mirroring some

other genetic site they are linked to. All I R G

we really know is we have found mark - H N , ers for some genes – and that’s about S E D

it.” SNPs are found in both coding A E N

regions for genes (and so could alter A J :

proteins) and non-coding regions N O I T

(where proximity to a gene can act as a A R T marker). There can be millions of S U L L SNPs in each human genome. I

“We have found half a dozen common variants, each of which could alter your relative risk by about one fifth”

CANCER WORLD I JULY/AUGUST 2008 I 23 Drug Watch

“We may never be able to answer how bad exactly it is to have two bad variants that interact”

With this level of information, not Turning to molecular studies on At least half of papers, in his estimation, much individualisation can be done – tumours, it is striking, says Ioannidis, have serious methodological problems and the human genome has been that despite the immense literature that could exaggerate their validation screened ‘pretty efficiently’ now. “At built up over the last 10 years, which is performance, especially for cross- best, we can explain maybe 5%–10% of more advanced than that on genetic validation (i.e. when not using new the variance of the genetic risk of peo - variance, the findings are modest. data). “Many are very complex studies ple getting these cancers – just a small For a start, an objective of improv - that require a lot of effort in design, amount of the total variability. But other ing survival by applying molecular sig - analysis and reporting, and are very rich tests – such as the PSA test for prostate natures has been tempered with more in data. Even minor divergences can cancer carried out on healthy men – are modest aims such as learning how produce huge biases.” crude measures with low predictive to use chemotherapy more effectively ability, so we may be doing as well and and to minimise unnecessary treat - MARKERS OF RESPONSE a bit better than before.” ment for those who would not benefit. Two very well known studies that Ioannidis says that going beyond “We are looking to improve the accu - include large sample numbers are identified variants that contribute to racy of classification for predicting the European-based MINDACT trial single individual risk means looking at what would happen to patients – where (Microarray in Node Negative Disease many common variants, some of which of course the classic application is in may Avoid ChemoTherapy – see also may contribute an amazingly small breast cancer.” Cancer World 7, July–August 2005), increase in risk. “And that is extremely So far, there has been a small gain in and, in the US, TAILORx (Trial difficult to pick up, even with very large predictability, says Ioannidis. “We could Assigning IndividuaLized Options for epidemiological studies.” Identifying classify 65 out of 100 people correctly Treatment), both of which are looking combinations is a daunting task – test - in the past. Now it is about 70. The at molecular signatures in node-nega - ing pairs of say a million each is 10 12 number depends on the participation of tive breast cancer to avoid unneces - interactions – testing for three is 10 18 , different subgroups of tumours you sary treatment and which are aiming for and pushes even our fastest computers have in your sample, so this is a simpli - patient numbers of 6,000 and 10,000 beyond their capability. “We may never fied statement, but the gain is modest.” respectively. “They are trying to vali - be able to answer well the question of That so much emphasis has been date the clinical performance of molec - how bad exactly it is to have two bad placed on the ‘hot results’ of gene pro - ular signatures and I am quite happy if, variants that interact.” filing is understandable, he adds, in as a result, we can just improve quality What the results do offer are oppor - such a rapidly blossoming field, but of life and minimise toxic side-effects,” tunities to pursue biological studies. there must now be a concerted effort to says Ioannidis. “If we have gene variants with P-values develop more rigorous methodologies. A good review article of the of 10 -20 – and sometimes we are getting “In particular, we must start much progress and practical limitations of to that high level of probability now – larger studies to improve the accuracy this technique, ‘Enabling personalized we can search for the genes related to of molecular signatures and to reduce cancer medicine through analysis of the variant and try and understand what the ‘noise’ level, and it would certainly gene-expression patterns’, has recently goes wrong. There is the possibility help if we have more robust validation been published in Nature (3 April they reflect biological pathways and and replication plans. Until now, most 2008) by Laura van ’t Veer and René machinery we do not really know about, are small studies on a few dozen or Bernards, pioneers of gene expres- and maybe we can develop new treat - maybe a few hundred samples, and val - sion profiling who developed the ments based on the research – but it is idation procedures have sometimes MINDACT signature (see also Cancer just a promise.” been very shaky.” World 12, May–June 2006).

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A feature of the molecular signatures 10,000 HUMAN GENOME PROJECTS that puzzles many outside the field is that there is little or no commonality The National Cancer Institute and cancer. The scale of the challenge is between the signatures of identified National Human Genome Research Insti - noted in a Scientific American article (18 genes for a particular disease such as tute (NHGRI) in the US has started to February 2007) by Francis Collins (direc - breast cancer. As Ioannidis explains, build The Cancer Genome Atlas, a hugely tor of the NHGRI) and Anne Barker: for this is probably because there are sev - ambitious project to map genomic the 50 most common cancers the effort eral genes that have the same effect on changes linked to cancer. Its pilot phase would be equivalent to 10,000 Human the cell cycle, carcinogenesis and the is examining three tumour types, Genome Projects in the volume of DNA spread of the tumour. Most of these glioblastoma, lung cancer and ovarian to sequence. genes are proliferation genes, he says. But having more commonality in the signatures and larger sample sizes should improve accuracy (and also that may not be independent from susceptibility for diseases such as type 2 reduce the majority of genes that are another. They should all be pursued.” diabetes, breast cancer and osteoporo - just ‘noise’ in most of the signatures The TAILORx and MINDACT sis, with as many as 50,000–150,000 currently used). trials do show that where there is back - participants, notes Ioannidis, while So with this ‘proof of concept’ and ing from funders, widespread colla- smaller numbers – but still over ten with large studies, Ioannidis’ guess is boration on large sample sizes for thousand – are involved in the search for that we will be able to increase correct molecular signatures has no barriers. variants for Parkinson’s disease. patient classification to about 80–85 But as Ioannidis also points out, there The good news, he adds, is that out of 100. The gene expression and is irony at present in the way that most researchers are now looking at com - microarray techniques used in trials of the studies are carried out when bining data on molecular signatures, such as TAILORx are not the only bio - compared with work on genetic vari - public availability of data is now greatly logical profiles that could show promise, ance. “The paradigm of molecular sig - improved (most databases were not he adds: “Microarrays and gene expres - nature studies is for one or two centres open to researchers only two to three sion is one level, and other levels to do research with a low number of years ago), and there are papers report - include proteomics, metabolomics, epi - samples, but often investigating a few ing convincing evidence that different genetics, nutrigenomics, and instead dozen or maybe several hundred gene labs can achieve similar results when of measuring messenger RNAs meas - expressions. But the genetic variance carrying out gene expression profiling. uring micro RNAs. They can all offer studies are now screening huge num - That may help to create greater con - complex biological pictures we can look bers of people for just a single gene sensus about exactly what results we are at, but again there are only pilot studies variant, or maybe a few.” seeing from studies. Ioannidis has an on very small numbers at present. We The genetic variance research did amusing example of one paper that need to investigate which techniques start with relatively few participants, could be interpreted as very positive to are best to take further.” but now there is work on populations of rather negative, and at several points in As with genetic variance, his take on 100,000 or more. “People will not be between – and which one you prefer what we are likely to see is a small, able to publish in major journals in this depends on your expectations. He con - incremental contribution from adding field unless they use massive platforms cludes: “Overall, the best we can cur - various techniques – again pointing to for genetic measurement, and that rently do is create stratification of risk the need for large-scale studies of even means massive sample sizes.” Consor - for certain subgroups – full individual - greater complexity. “Each is a snapshot tiums are now looking at variance and isation is far away.”

“Where there is backing from funders, widespread collaboration on large sample sizes has no barriers”

CANCER WORLD I JULY/AUGUST 2008 I 25 Master piece

A scientist without borders

§ Janet Fricker

A biostatistician with medical training, Hélène Sancho-Garnier helped drive the shift towards evidence-based clinical practice in the ’60s and ’70s. Stepping nimbly over traditional boundaries, she went on to apply this approach to cancer registries, screening, and now prevention and the ultimate challenge of how to communicate health messages to stroppy teenagers.

n addition to her many achievements in the the other died in the gas chambers. Her mother was fields of oncology, biostatistics and public health, taken for questioning by the Gestapo after a search IHélène Sancho-Garnier has the distinction of revealed a typewriter on the shop’s premises. Happily being born on September 3rd 1939 – the day World it was broken and they were unable to prove that she War Two broke out. Her career has spanned the ini - had used it to forge resistance documents. tiation of clinical trials in France, the launch of can - Sancho-Garnier has few memories of occupied cer registries and the development of screening Paris – the knowledge came later when her mother told programmes. Throughout this disparate work runs a the teenage Hélène and her older brother Gérard and common theme – the need to introduce evidence- younger sister Michèle the story of her war. She recalls based practices into all aspects of medicine. Today the a happy, carefree childhood. “They called me Papillon full force of her fighting spirit is focussed on Epidaure, because I danced along the boulevards, jumping over the education centre for cancer prevention in Mont - the stones. I was a garçon manqué , spending my time pellier, where she is taking on the challenge of find - ice skating, swimming and playing tennis.” ing strategies for communicating to France’s young Academic studies came easily to her. “The decision people, and for evaluating the proposed strategies. to study medicine was greatly influenced by the area of Having grown up on the left bank of the Seine, Paris in which we lived. Doctors came to the shop and Sancho-Garnier remains at heart a Parisian, but with my school friends had fathers who were doctors, so it an Iberian twist from her marriage to Spaniard Isabelo seemed the natural thing to do. I longed for adventure Sancho-Lopez. Early years were inevitably domi - and had romantic visions of working in Africa.” nated by the war. Just three days after Hélène’s birth, In 1959 Sancho-Garnier enrolled in medical her father, the proprietor of a bespoke shirt making school. Student days were dominated by politics, business in the Boulevard St Germain, went to the organising demonstrations against the brutal sup - front. He would be away from his young family for pression of the Algerian independence movement. three years after being taken prisoner. Two uncles She is clearly a woman who does nothing by halves. fought for the French resistance – one was shot and Politics was so all-consuming that it threatened to

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sabotage her medical career, as she could not find the first ever clinical trial in France, randomising babies time to sit the examinations ( internat ) required for with angiomas to receive radiotherapy or no treat - French doctors to work as clinicians in hospitals. ment. When Eschwege went on maternity leave she Pathology was one option she was qualified to take asked Sancho-Garnier to mind her project. The that would enable her to work in a hospital, so she study, which showed angiomas resolved just four decided to move to the Gustave Roussy Institute, the months faster with treatment than without, led to the biggest cancer centre in Paris, to complete her publication of Sancho-Garnier’s first paper, and studies. Here she buckled down, sitting her hospital brought her to the attention of Daniel Schwartz, examinations, and becoming interested in skin can - who was in the process of setting up the first medical cer. She divided her time between seeing patients in biostatistics school in France, and was head of a the morning and working in the lab in the afternoon. research unit at INSERM (France’s National Insti - A career defining moment was a meeting with tute of Health and Medical Research). In 1964, Evelyne Eschwege, a young scientist organising the Schwartz recruited her to his research unit. Part of the

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attraction of the career change was her competitive working and needed a bit of light relief. Sancho- relationship with her brother G érard, now a profes - Lopez’s family came from Toledo, but had been sor of physics, who had always ribbed her about forced into exile in France and Brazil after fighting medicine requiring no more than good memory Franco in the Civil War. The couple soon had three skills. “I wanted to prove to him that I was perfectly children – Marie Christine born 1964, Isabel born capable of doing some kind of maths,” she says. 1967 and Xavier born 1969. Sancho-Garnier acknow- In her new role, Sancho-Garnier divided her ledges the unswerving support of her maternal grand - time between clinical work in cancer dermatology at mother, Marie, then a vigorous 80-year-old, who the Gustave Roussy and providing biostatistical sup - kept the household going during this busy period. port to a growing number of oncology trials and clin - She and her husband divorced in 1976, but she ical research projects, driven by Robert Flamant, still thinks that, overall, marriage was a positive expe - Schwartz’s first medical élève and head of the first bio - rience. “We had three wonderful children together statistical unit at the Gustave Roussy. She also devel - and he taught me the Spanish language and culture.” oped an interest in prognostic evaluation – looking at Sancho-Garnier never remarried. “With three chil - how best to adapt treatments to the individual char - dren it would have been difficult to find someone, and acteristics of patients and their tumours – and in epi - I wasn’t looking,” she says, adding with Gallic candour demiological studies of the causes of cancer. that life has not been without its divertissements . It was an extraordinarily productive period. She inevitably appeared as second author on a great A CAREER WOMAN many papers, and also wrote her own papers taking With the marriage over, she threw herself whole - an overview of the concept of clinical trials. She heartedly into her career. “I have a big capacity for reviewed issues such as knowledge acquisition from work. Early on I learnt that for women to have suc - randomised trials and their role in establishing treat - cessful careers they can’t afford to spread them - ment policies. Sancho-Garnier can take some credit selves too thin. Many women prefer to have all sorts for placing the concept of clinical trials on the med - of other things than work in their lives, then it’s to be ical agenda. “Being medically trained, it was easier for expected that they are overtaken by male colleagues.” me to ask the clinicians to introduce good method - ology into their clinical trials. I understood the clin - ical perspective and ethical difficulties.” At the same time as launching her career, Sancho- Garnier was juggling further training (taking degrees in both biostatistics and head and neck cancer) and raising three children. In 1963 she had married Isabelo Sancho-Lopez, a Spaniard working for the Organisation for Economic Co-operation and Devel - opment in Paris. The couple had met on a blind date organised by her sister, who thought she was over -

Designed to inspire. Sancho-Garnier with her team at the Epidaure cancer prevention centre in Montpellier (photomontage). The bold architecture provides a stimulating setting for the school children who visit Epidaure’s interactive health education centre Sancho-Garnier can take some credit for placing the concept of clinical trials on the medical agenda

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An internationalist. Sancho-Garnier has always sought to extend her contribution beyond the borders of France. She is pictured (right) at an oncology congress in Cairo in the mid-1970s, while she was still based at the Gustave Roussy Institute. The picture below was taken in 2007 at a screening training session at the National Cancer Institute of Uruguay, which she helped organise in her role as the UICC strategic lead for prevention and screening

Garnier was recruited to a healthcare commission, headed by Maurice Tubiana, set up to organise the first large-scale breast screening programmes in France. The commission discovered that a majority of the mammography machines in use were obsolete and set about lobbying the Department of Health to The hard work paid off in 1988 when she was lay down mandatory minimum standards and qual - appointed head of the biostatistical department of the ity control. This was probably the biggest benefit to Gustave Roussy, after Flamant was promoted to come out of organising these large-scale programmes, director of the Institute. With success came oppor - as opportunistic screening was already being used by tunities to play a role on France’s national oncology 40% of the population. stage. Highlights included involvement in the Quality assurance is essential, she says, to keep National Commission for Cancer, with Yves Cachin false-positives and false-negatives to a minimum.As as chairman, which recognised for the first time the mammography uses ionising radiation, it is also importance of population-based cancer registries. important to ensure the equipment is working cor - “Cancer registries are vitally important to meas - rectly, the proper techniques are used and regular test - ure the burden of different cancers. They help ing doesn’t start too early and isn’t done too frequently. resource planning, flagging up where we need to do She is uneasy about the screening that is being epidemiological research, and can be a way of eval - undertaken in younger women with genetic suscep - uating prevention initiatives.” tibilities to breast cancer “The gland tissue is more The commission proved a challenge, as it would sensitive to ionising radiation and, because of the den - have been hugely expensive to produce a national reg - sity of the breast, mammography is less sensible as it istry. “We’ve solved this problem by having coverage leads to more false-negatives,” she says. of 10%–15% of the territory with separate registries, Particular issues arise in developing countries, which can be used to estimate what’s happening in where mammography machines are of dubious the rest of the country.” quality and inadequate treatment infrastructure is in Screening became an area of expertise. After place. “If you don’t have good structures for diagno - landmark trials from Sweden showed that breast sis and care, you’re doing more harm than good,” screening results in 30% fewer deaths, Sancho- she says. “Where the extent and quality of the

CANCER WORLD I JULY/AUGUST 2008 I 31 Master piece

infrastructure are insufficient, it is important to Today she remains based at the Epidaure, an educa - implement adequate structures and professional tion and training centre housed in an innovative training before organising any screening programme.” building resembling a space shuttle. “The building was designed to inspire the imagination and show FROM SCREENING TO PREVENTION children there are no limits,” she says. It was Sancho-Garnier’s expertise in screening that Each day parties of school children visit to helped her to make the career transition from bio - increase their understanding of health prevention and statistics to public health. In 1991 she was appointed hopefully change their behaviour. One of the high - head of INSERM’s cancer epidemiological research lights of the two-hour tour is a smoking machine that unit, where she managed a department of more than graphically illustrates how tar accumulates in the 40 people in addition to her work at the Gustave lungs. There is also an interactive film where you can Roussy. To her disappointment, the atmosphere was change the lives of actors according to the interven - not particularly easy, and she tired of the internecine tions they take. While the activities are principally for fighting between her staff. With her children having children in the Languedoc-Roussillon region, the cen - left home, she felt weary and ready for a change. tre has produced tool kits and training to enable A chance remark at a dinner to Henri Pujol, cre - teachers across France to introduce health education ator of the Epidaure cancer prevention centre, about messages throughout the French national curriculum. how much she liked the city of Montpellier, eventu - Help is on hand for subjects as diverse as History, ally resulted in a job offer to head the Epidaure (part Maths, Science, Physical Education, French and of the regional cancer centre), together with a chair English. “Hearing the same messages across all their in Public Health at the University of Montpellier. lessons helps to consolidate the children’s health “I loved Montpellier’s architecture and climate, and behaviour,” she explains. I felt its proximity to the Spanish border combined my Teenagers pose particular challenges for the unit. French and acquired Spanish culture,” she says. “They’re always argumentative. If you say it’s red, they’ll say no it’s black. They live for the moment, and don’t care in the least about future health risks.” With such formidable challenges, might it not be easier to just leave them well alone until they grow up and become more receptive to messages? This, says Sancho-Garnier, would be totally irresponsible. “It’s a particularly dangerous time, when young people are at risk from alcohol damage and becoming addicted to tobacco and other drugs. They’re starting their sexual lives and risk

Kids! Marie-Christine, Isabel and Xavier, demonstrating the teenage capacity to live for the moment. Sancho-Garnier brings a mother’s experience to the task of developing strategies for communicating health messages to this difficult age-group “Teenagers live for the moment, and don’t care in the least about future health risks”

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“I want to teach my grandchildren the importance of being critical... I want them to ask for the evidence”

exposure to HPV and HIV. You have to try and convince them to take the best possible care of themselves.” Critical young minds. The best strategy for getting Subjected to all the through to teenagers that Epidaure usual manipulative has used is the peer mentor tech - messages from the nique, where younger teenagers are tobacco, food and paired with older teenagers who help drinks industries, show them appropriate behaviour. Sancho-Garnier’s They are also developing tools to grandchildren are show teenagers how they are manip - valuable and willing ulated by various publicity tech - guinea pigs for niques, particularly from the tobacco, testing prevention food and alcohol industries. strategies Coming from her background in biostatistics, Sancho-Garnier took time to appre- preparing a handbook for the Mediterranean region. ciate the full dimensions of education. Her current Like most successful women, Sancho-Garnier’s ambition is to incorporate scientific methods into career has not been without sacrifices. “My children prevention. now tell me that I wasn’t home enough when they “In medicine I was one of the first people to were young. I have no big regrets. To function as a introduce an evidence base for clinicians. Now I’m mother I needed to feel fulfilled in my career.” working with educators I want to incorporate the The children, one senses, rebelled by not follow - same scientific rigour and introduce ways of properly ing traditional academic paths. Marie Christine was evaluating the effectiveness of prevention and the full an airhostess before giving up work to care for her impact of our contact with children,” she says. family, Isabel works as a marketing manager in Madrid, while Xavier works in the construction STILL AN INTERNATIONALIST industry. Her six grandchildren offer the opportunity Since 1998, Sancho-Garnier has served as the French for reinvention and the healing of past differences. representative at the International Union Against Ranging in age between one and 13, they also provide Cancer (UICC). It is a venture that is particularly willing guinea pigs to road-test her health education close to her heart, as she is keen to improve the sit - messages. “Above all I want to teach my grandchil - uation of people with cancer in developing countries, dren the importance of being critical, and not just focussing on French- and Spanish-speaking regions. accepting the things they are told. I want them to ask In 2002 she became the UICC’s strategic leader for the evidence,” she says. for prevention and early detection. Among her Retirement is not a subject she cares to dwell on, many achievements is the publication of a handbook although she is amused that for once this is an area reviewing the evidence for different cancer pre- where being a mother of three works in her favour. “In vention strategies, with editions for Europe, Latin France, as a university professor who has had three America and South Asia. “The idea is to help gov - or more children, you can work for an extra year,” she ernments to prioritise the interventions that are says. “I don’t want to retire, there’s still lots to achieve important, and the situation varies in different and I really do want to get further in providing an evi - areas,” she says, adding that they are currently dence base for primary prevention.”

CANCER WORLD I JULY/AUGUST 2008 I 33 Spotlight on...

Tackling cancer in the Middle East

Euro-Arab School of Oncology contributes a mix of international and local expertise

§ Jim Boumelha

Cancer is now the fastest growing killer in theArab world. There is an urgent need to train health professionals on strategies for prevention, screening and appropriate care, and convince governments to act. ESO hopes to contribute to this effort through its Euro-Arab partnership.

or several centuries theArab was first conceived” said Aloisi, “we had have so far responded and, as their num - world has been viewed by high hopes but little experience.” bers increase, two or three seats will be European rulers and power - Gadallah, now co-chair of the organ - added onto the executive, which will brokers with a mix of suspi - isation, traces the swift progress of EASO be held in rotation. Gadallah expects that cion of its colonial advances to its sound foundation: an agreement when EASO attains a critical mass – iFn Europe’s southern and eastern flanks signed in 2005 between ESO and the hopefully by November – it will be able to and curiosity about its cultures and Egyptian Ministry of Health and Popula - move from relying on personal contacts to advances in science, in particular medi - tion. “We used our first event, Advances function through the focal points for - cine. In modern times the New Arab in Clinical Oncology, in Cairo in March mally designated by each country. There World is slowly emerging from decades of 2006, to attract practitioners from other are plans to raise the issue at the meeting societal and political turbulence to Arab countries,” says Gadallah, “as well as of health ministers of theArab League, to become once again an inevitable partner Egypt, they came from Libya, Lebanon, harness their support and engagement. for Europe. The exchange of ideas and Yemen, Sudan and Saudi Arabia. We At its heart, however, EASO is based information is flowing again in many fields knew then we were handling it right.” closely on the model that has been tried including medicine and, above all, the This was followed by a masterclass in and tested to great effect by ESO over the fight against cancer. The Euro-Arab Cairo, an EASO course in Alexandria, past 26 years, saysAloisi: bringing together School of Oncology (EASO) is one of and, most recently, an EASO lung cancer young oncologists, who have completed the most recent manifestations of this. course in Damascus, in cooperation with their formal training, to learn from top EASO first emerged as a good idea Al Bairouni teaching hospital and the international experts, to help reduce the from discussions between enthusiasts Syrian Oncology Association. number of diagnoses that are mistaken or including Mohsen Gadallah, epidemiol - The bureaucracy is, and will probably too late, and avoid needless suffering ogist at Cairo’s Ain Shams University, remain, very light, as EASO is run by from inappropriate treatment. Alberto Costa, director of the European an executive committee of three. The The Arab world covers 300 million School of Oncology (ESO) and emphasis has been on encouraging health people, with a wide social, economic and Francesco Aloisi, former Italian Ambas - ministries in otherArab countries to nom - cultural diversity and spread across 22 sador to Egypt, and they nurtured it step inate a country representative as a ‘focal countries. Inevitably, due to environ - by step until it became a reality. “When it point’ – the link person with EASO. Eight mental, genetic and other factors, the

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Spreading the news. A well- attended press conference at the Damascus masterclass provided an opportunity for local journalists to learn about the scale of the problem and what needs to be done... and to ask questions about how Syria is gearing up to confront its growing cancer problem E R Y T N I c M R E T E P incidence of different cancers varies from When EASO first started to look one society to the next, as do the barriers for a venue outside Egypt, it con - to effective cancer control. Adapting to tacted several countries. Syria local conditions is therefore a core chal - was selected not just because the lenge facing EASO. To tune in to the Syrian group of academics made needs of the society concerned, says a serious offer, but also due to the support cancer deaths, “it is changes in lifestyle Gadallah, the first step must always be to expressed by the Syrian authorities. and behaviour that have become the over - consult with the local specialists. Today the fight against cancer is gain - whelming factors.” She mentions in par - “When we select a country for a sym - ing currency with ministries of health ticular that people are tending to eat more posium, we study the most prevalent can - throughout the Middle East, partly meat while reducing their fruit and veg - cer in the area and we concentrate our because of the increasing work under - etable intake, adding that “40% of cancer symposium in this area. The country that taken by the Eastern Mediterranean cases can be prevented through changing hosts the programme will benefit from Regional Office of the World Health lifestyle and behaviour and others can experts coming from Europe to talk about Organization (EMRO), but also because be treated if diagnosed early.” the problem in this country. Of course we of the growing incidence of the disease in EASO is determined to play its part in cannot cover all problems of all Arab the region. EMRO estimates that cancer helping the region address this escalating countries, but there are some they have in is currently the fourth highest cause of threat from cancer, but it understands that common – lung cancer for instance.” death in the region, with breast, bladder, trying to import solutions developed for But EASO is also keen to go beyond lung, mouth and colon being the most the European context won’t do the trick. specialists at local cancer societies or common sites. Around 240,000 people “It’s not a case of one party imparting teaching hospitals, to involve govern - die from the disease each year and, alarm - knowledge and the other absorbing it,” ments, says Gadallah, “We have to be ingly, this figure is expected to more than says Gadallah. “Our own experience was sure that the ministry of health is repre - double by 2015. also taught at the last three events, and we sented as well as academics. Only then According to Ghada Muhjazi (pic - try to make it an equal exchange of ideas. can recommendations for a cancer plan, tured above, right), from EMRO’s Dam - For example, in Europe they use mam - or for early detection or a new protocol for ascus office, while an aging population mography, but in this region we think management, be taken further.” accounts for some of this projected rise in that breast examination can be more

CANCER WORLD I JULY/AUGUST 2008 I 37 Spotlight on...

In many Arab countries effective. We don’t use exactly what is Region % Diagnosed late (breast) used in Europe – we modify it to fit with more than 65% of breast Nile delta, Egypt 70% our culture and our society.” cancers are diagnosed Syria 73% Teaching remains at the core of the at an advanced Sudan 78% mission, but there are many other issues stage (III or IV) Cairo, Egypt 66% that EASO organisers recognise must be Jordan 69% confronted, such as health education and Tunis, Tunisia 49% (40% > 5cm) the infrastructure and organisation of Source: Cancer in EMRO Iraq 47% cancer services, which involve interacting powerpoint presentation, Bahrain 33 % (70% > 2 cm) with authorities and decision makers. WHO Syria One big challenge is setting up nat- ional cancer registries, which do not exist in Damascus provided the opportunity for society is essential to ensure that author - in 50% ofArab countries. For epidemiol - journalists to pose questions not just ities take action. He cites the work done ogists like Gadallah this is a major prob - about the technical and medical aspects by his organisation, theAssociation tunisi - lem, as they can deal only with estimates, of prevention, screening and care, but enne contre le cancer, which has now usually extrapolated from a hospital-based also about what action the authorities emerged as the authority on cancer in his study. “These research findings cannot be are taking. One journalist wanted to know country. “We organise international sym - strong so long as they don’t originate from what had happened with the Syrian can - posia on all aspects of cancer and, at the a national cancer registry,” he insists. One cer registry – he’d heard a great deal of talk same time, we feel free to mobilise civic idea gaining momentum is to set up a sin - since 2000, but had so far seen no evi - society whenever we need lobbying on gle registry to cover all theArab countries. dence of it.Another commented that it is major issues,” he said. He has been look - Early detection is another major chal - hard to get stories about smoking and ing for ways to get other countries in the lenge, a key part of which involves setting the related health problems into news - region involved in this work, and hopes to up appropriate, quality-controlled screen - papers, speculating that cigarette com - bring in the Tunis-basedALESCO (Arab ing programmes. Cancer tends to be panies are very powerful and have links League Educational Scientific and Cul - picked up quite late throughout most of with the newspaper owners. tural Organization). “Any pan-Arab organ - the Middle East. In breast cancer, for Such scepticism is, perhaps, under - isation must be supranational, to make it instance, 65%–75% of cases are picked up standable, given the schizophrenic easier for all countries to feel at home.” at an advanced stage in countries such as approach many governments have to the Though still in the early years of its Jordan, Syria, Egypt and Sudan. EASO is tobacco industry. In Damascus, for own pan-Arab mission, EASO is rapidly looking at the possibility of running mas - instance, just as the ministry of health was accumulating valuable experience of terclasses on screening techniques and welcoming the EASO symposium on working with authorities, bringing teaching epidemiologists how to conduct lung cancer, the deputy minister for eco - together practitioners from different hori - effective national screening programmes. nomic affairs was splashed all over Syrian zons and pressing its own distinct agenda Involving ministries of health in the TV launching a new cigarette factory as of patient-centred care. With a week- activities of EASO clearly makes sense in part of a deal with the British-American long masterclass on clinical oncology terms of getting politicians and policy Tobacco Company. The media, and the scheduled for Cairo at the end of Novem - makers to focus on these challenges and public, have good reason to question how ber, and plans to steadily increase the work in the same direction. The question, this squares with the WHO Framework number of topics addressed and loca - as always, is how to get governments to Convention on Tobacco Control, to tions used, EASO is quietly building match their rhetoric with action? which Syria is a signatory. a constructive cooperation between A press conference organised by Tunisian oncologist Farhat Ben Ayad European andArab oncologists built on a EASO at the end of its latest symposium believes that the involvement of civic genuine dialogue and shared goals. The question, as always, is how to get governments to match their rhetoric with action?

38 I CANCER WORLD I JULY/AUGUST 2008 Impact Factor

Does prophylactic cranial irradiation reduce the incidence of brain metastases in extensive small-cell lung cancer?

§ Lia Halasz and Noah Choi

A phase III study has shown that prophylactic cranial irradiation decreases the risk of symptomatic brain metastases and may improve overall survival for patients with extensive small-cell lung cancer and response to systemic chemotherapy.

rain metastasis is a major cause of survival and lower cumulative incidence of disease-free survival (14.7 weeks com - morbidity and mortality in patients brain metastasis in patients treated with pared with 12.0 weeks in the control Bwith small-cell lung cancer. Pro - PCI compared with controls.According to group), longer median overall survival phylactic cranial irradiation (PCI) is used the analysis of the four total doses (8 Gy, from randomisation (6.7 months vs to treat microscopic or subclinical metas - 24–25 Gy, 30 Gy and 36–40 Gy), larger 5.4 months), and a higher one-year tases that are protected from cytotoxic doses of radiation led to greater decreases survival rate (27.1% vs 13.3%). drugs by the blood–brain barrier. Since in the risk of brain metastases. 1 In this study, brain imaging was not the 1970s, many trials have evaluated Slotman and colleagues performed a performed before randomisation unless the role of PCI in patients with small-cell phase III study to address the role of PCI symptoms indicative of brain metastases lung cancer, but have produced incon - in patients with extensive small-cell were present. Published data indicate, clusive results regarding survival benefit. lung cancer who showed any response to however, that approximately 13% of In 1999, Aupérin et al. conducted a 4–6 cycles of systemic chemotherapy patients with small-cell lung cancer have meta-analysis of seven trials that included (see opposite). The PCI and control asymptomatic brain metastases at the time 987 patients who were in complete remis - groups (each with 143 patients) were of diagnosis. 2 Such patients would require sion after chemotherapy for small-cell lung well balanced with regard to baseline a therapeutic dose of radiation (generally cancer (86% had limited disease), in order characteristics. The cumulative risk of 35 Gy in 14 fractions) rather than a lower to assess the efficacy of PCI. 1 This study brain metastases within one year was dose in the range used for PCI. showed a 5.4% higher three-year survival 14.6% in the PCI group compared Conventional wisdom suggests that rate (20.7 % in the PCI group vs 15.3% in with 40.4% in the control group. PCI PCI would not provide survival benefit in the control group), longer disease-free was associated with a higher median patients who have uncontrolled disease at

Lia Halasz is a resident in the Harvard radiation oncology residency programme at Harvard Medical School, and Noah Choi is professor of radiation oncology at Harvard Medical School, distinguished scholar in thoracic oncology at Massachusetts General Hospital Cancer Center and director of thoracic radiation oncology at Massachusetts General Hospital, Boston, Massachusetts, USA. This article was first published online in Nature Clinical Practice Oncology on 22 April 2008, and is reproduced with permission. www.nature.com/clinical practice, doi:10.1038/ncponc1125, © 2008 Nature Publishing Group

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the primary or distant metastasis sites, or 20 Gy in five fractions in order to minimise 2. T Seute et al. (2006) Response of asymptomatic both, because of the likelihood of reseed - the length of treatment. To improve the brain metastases from small-cell lung cancer to ing to the brain after such treatment. therapeutic ratio of PCI, it is reasonable to systemic first-line chemotherapy. J Clin Oncol Slotman and co-workers, however, use a standard fractional dose of 2 Gy for a 24:2079–2083 demonstrated survival benefit of PCI in a total dose of 30–34 Gy in patients with a 3. B Slotman et al. (2007) Prophylactic cranial setting where the majority of patients good performance status and a complete irradiation in small-cell lung cancer: the authors had persistent disease at the primary response to systemic chemotherapy. 5 reply. N Engl J Med 357:1977–1978 (76%) and/or distant (71%) sites. 3 Overall, this study provides good evi - 4. A Gregor et al. (1997) Prophylactic cranial Consistent with previous trials of dence that PCI is beneficial for patients irradiation is indicated following complete response PCI, 4 no difference was found in cognitive with extensive small-cell lung cancer and to induction therapy in small cell lung cancer: functioning or global health status among any response to systemic chemotherapy. results of a multicentre randomized trial. Eur J the two study arms after short-term fol - Cancer 33:1752–1758 low-up; however, fatigue and hair loss References 5. R Suwinski et al. (1998) Dose-response adverse events were reported significantly 1. A Aupérin et al. (1999) Prophylactic cranial relationship for prophylactic cranial irradiation more often by patients in the PCI arm. irradiation for patients with small-cell lung cancer in in small cell lung cancer. Int J Radiat Oncol Most patients received PCI at a dose of complete remission. N Engl J Med 341:476–484 Biol Phys 40:797–806

Synopsis B Slotman, C Faivre-Finn, G Kramer et al. (2007) Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med 357:664–672 Background. Brain metastases are common in patients with small-cell lung cancer and indicate a poor prognosis. The role of prophylactic cranial irradiation (PCI) in patients at high risk for symptomatic brain metastases who do not experience a complete response to chemotherapy is unclear. Objective. To determine whether PCI can reduce the incidence of symptomatic brain metastases in patients with extensive small- cell lung cancer. Design. In the period February 2001 to March 2006, this randomised, multicentre, phase III trial enrolled 286 patients with histologically or cytologically confirmed extensive small-cell lung cancer.All patients had to have experienced a response to chemo- therapy in order to be eligible. Specific inclusion criteria included age between 18 and 75 years, WHO performance status of 0 to 2, response following 4–6 cycles of chemotherapy, no evidence of brain metastases, no previous radiotherapy to the head or neck, and no other cancer. Intervention. Patients were randomly assigned to undergo PCI ( n=143) or to receive no therapy ( n=143). Radiation was specified to the midline and delivered on a schedule of 4–5 fractions per week using one of the following schedules: 20 Gy in 5 or 8 fractions; 24 Gy in 12 fractions; 25 Gy in 10 fractions; or 30 Gy in 10 or 12 fractions. Radiotherapy had to commence 4–6 weeks after chemotherapy. When any symptoms indicative of brain metastases were present, CT or MRI was performed. Outcome measures. The primary outcome was the development of symptomatic brain metastases. Secondary outcomes included survival, toxic effects, quality of life and treatment costs. Results . Symptomatic brain metastases were observed in 24 patients in the treatment group and in 59 patients in the control group. For the irradiation group, the hazard ratio for symptomatic brain metastases was 0.27 and the cumulative risk of metastases was 4.4% at six months and 14.6% at 12 months. The corresponding cumulative risks in the control group were 32% and 40.4%, respec - tively. Median survival without disease progression in the irradiation group was significantly longer than that in the control group, (14.7 vs 12 weeks; P=0.02) and median overall survival was significantly longer in the irradiation group than in the control group (6.7 vs 5.4 months; P=0.003). Survival rates at one year were 27.1% and 13.3% in the irradiation and control groups, respectively. Acute reactions associated with irradiation included headache, nausea and vomiting, fatigue and skin reactions. Conclusion. The incidence of symptomatic brain metastases is reduced after PCI in patients with extensive small-cell lung cancer who have experienced a previous response to chemotherapy. Acknowledgement: The synopsis was written by Mandy Aujla, Associate Editor, Nature Clinical Practice.

CANCER WORLD I JULY/AUGUST 2008 I 41 Impact Factor

Comparison of gemcitabine plus platinum analogue with gemcitabine alone in advanced pancreatic cancer

§ Eileen O’Reilly and Ghassan Abou-Alfa

A pooled analysis of two randomised trials has shown that gemcitabine in combination with a platinum analogue (cisplatin or oxaliplatin) is a potential front-line treatment option in advanced pancreatic adenocarcinoma.

reatment for advanced pancreatic while the German multicentre trial inves - meta-analysis. 2 A potential weakness of adenocarcinoma remains a major tigated the use of a gemcitabine and cis - the pooled analysis is that the experi - Ttherapeutic challenge. In 2008, platin regimen. The summation of data mental arm included both standard international standards of care include from these trials indicated that combining 30 min and fixed-dose rate (protracted single-agent gemcitabine, gemcitabine gemcitabine with either oxaliplatin or cis - infusion) gemcitabine schedules in com - and erlotinib 1 and arguably gemcitabine- platin, enhances progression-free survival bination with cisplatin or oxaliplatin. based cytotoxic combinations that include (HR 0.75, P=0.0030) and overall sur - Of note, and somewhat contrary to the a platinum agent or an oral fluoropyrim - vival (HR 0.81, P=0.031) when com - conclusions by Heinemann and col - idine. The pooled analysis performed by pared with gemcitabine alone. The leagues, are the preliminary results of the Heinemann and colleagues (see opposite) benefits associated with combination ECOG 6201 trial, which did not suggest adds to the collective evidence that sup - therapy were most pronounced in patients a benefit of a gemcitabine–oxaliplatin- ports the use of a gemcitabine-based with a good performance status (HR 0.82, based combination over single-agent cytotoxic combination in patients with P=0.063). gemcitabine. 3 either locally advanced or metastatic pan - The pooled analysis overcomes some Given the recent disappointing results creatic adenocarcinoma and good per - of the limitations of small individual trials of phase III trials of gemcitabine in com - formance status. 2 – the conclusions of which can be limited bination with the antivascular agent beva - This pooled analysis combines two by a lack of statistical power – and is cizumab, 4 or the monoclonal antibody important trials conducted in Europe. strengthened by assessment of individual cetuximab 5 (wherein no benefit was noted The French Multidisciplinary Clinical data points. Furthermore, the results of over single-agent gemcitabine in either Research Group (GERCOR)/Italian this pooled analysis support the well- study), the relative utility of a cytotoxic Group for the Study of Gastrointestinal recognised value of performance status in combination can be appreciated. Themes Tract Cancer (GISCAD) study compared delineating patient outcomes. Notably, are consistent for cytotoxic combinations, single-agent gemcitabine with a gem- the conclusions are similar to those drawn with improved response rates, time-to- citabine and oxaliplatin combination, by Sultana and colleagues in a larger tumour progression and clinical benefit

Eileen O’Reilly is an associate member, and Ghassan Abou-Alfa is a medical oncologist, at Memorial Sloan-Kettering Cancer Center, and Eileen O’Reilly is an associate professor of medicine, and Ghassan Abou-Alfa is an assistant professor of medicine, at Weill Cornell Medical University, New York, USA. This article was first published online in Nature Clinical Practice Oncology on 29 April 2008, and is reproduced with permission. www.nature.com/clinical practice, doi:10.1038/ncponc1128 , © 2008 Nature Publishing Group

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Synopsis V Heinemann, R Labianca, A Hinke et al. (2007) Increased survival using platinum analog combined with gemcitabine as compared to single-agent gemcitabine in advanced pancreatic cancer: pooled analysis of two randomized trials, the GERCOR/GISCAD intergroup study and a German multicenter study. Ann Oncol 18:1652–1659 Background. Several randomised trials have demonstrated an improved survival in patients with advanced pancreatic cancer treated with gemcitabine plus a platinum analogue compared with patients treated with single-agent gemcitabine; however, none of these studies has shown a statistically significant survival advantage of combination therapy. It has become clear that trials enrolling larger numbers of patients are needed to prove a statistically significant benefit of therapy with gemcitabine plus a platinum analogue. Objective. To determine whether treatment with gemcitabine plus platinum results in better overall survival than treatment with single-agent gemcitabine in patients with advanced pancreatic cancer. Design and intervention. This was a pooled analysis of single-patient data from the French Multidisciplinary Clinical Research Group (GERCOR)/Italian Group for the Study of Gastrointestinal Tract Cancer (GISCAD) intergroup study ( n=326), which compared gemcitabine plus oxaliplatin with gemcitabine, and the German multicentre study ( n=195), which compared gemcitabine plus cisplatin with gemcitabine. Both trials had similar inclusion and exclusion criteria and both recruited patients with histo- logically proven, unresectable, metastatic or locally advanced pancreatic cancer. Outcome measure. The main outcome measure was overall survival (OS). Results. Data were available for 503 patients, 252 of whom were treated with gemcitabine plus a platinum analogue and 251 of whom were treated with single-agent gemcitabine. Overall response rates were significantly higher in patients receiving gemcitabine plus a platinum analogue than among those receiving single-agent gemcitabine (22% vs 14%; P=0.028). The median progression- free survival (PFS) for the study population as a whole was 18 weeks. Pooled univariate analysis of PFS revealed a hazard ratio (HR) of 0.75 in favour of combination therapy ( P=0.0030). Subgroup analysis revealed that the beneficial effect of the combination reg - imen on PFS was greater in the group of patients with locally advanced disease than in the group of patients with more widespread disease (35 vs 21 weeks; P=0.051). In addition, among patients with a good performance status, those receiving combined chemo- therapy experienced a longer median PFS than patients treated with single-agent gemcitabine (33 vs 14 weeks; P=0.013). Median OS for the whole cohort was 33 weeks, OS was significantly greater in patients receiving combination chemotherapy than in patients receiving gemcitabine alone (HR 0.81, P=0.031). The most important predictors of prognosis were stage of disease ( P<0.0001) and performance status ( P<0.0001). Subgroup comparisons among patients receiving combination therapy revealed significantly longer OS in patients with good performance status (ECOG status 0) than in patients with more aggressive disease (52 vs 36 weeks; P=0.063). Conclusion. The results of this pooled analysis reveal that, in comparison with single-agent gemcitabine therapy, treatment with the combination of gemcitabine plus a platinum analogue significantly improves OS and PFS in patients with advanced pancre - atic cancer. Combination therapy seems particularly beneficial in patients with a good performance status. Acknowledgement: The synopsis was written by Mandy Aujla, Associate Editor, Nature Clinical Practice. being relatively constant across studies. balanced against the potential benefits. adenocarcinoma, thus far, has been dis - The consistency of these results indi - Notwithstanding the modest incre - appointing and, in relative terms, cyto - cates that in patients with good perform - mental value of the treatment option sug - toxic-based combinations are enjoying ance status and symptomatic or bulky gested by the results of the pooled analysis an indirect re-endorsement. Hence, treat - disease, a cytotoxic-drug-based combi - (i.e. a gemcitabine-based combination), ment options in 2008 include single- nation is a justifiable treatment consid - much needs to be done to improve the agent gemcitabine, gemcitabine-based eration. It is currently unclear whether treatment options for all stages of pan - cytotoxic combinations, gemcitabine and two-drug combinations or combinations creatic adenocarcinoma. The identifica - erlotinib and, where possible, an empha - comprising three or more drugs will con - tion of new active drugs against novel sis on clinical trial participation. fer optimum benefit over gemcitabine. pathways integral to tumour growth and In addition, the extra toxicity incurred survival is fundamental.An early venture Details of the references cited in this article can from multi-drug combinations needs to be into the ‘targeted world’ for pancreatic be accessed at www.cancerworld.org/magazine

CANCER WORLD I JULY/AUGUST 2008 I 43 Impact Factor

N EWS R OUND Selected reports edited by Janet Fricker

Shorter radiotherapy UK researchers have now carried out two of distant metastasis and overall risk of death at prospective studies randomly allocating women five years among women treated with the courses may not increase to different radiotherapy regimens and follow - hypofractionated schedule, as well as lower risk of breast cancer relapse ing them up for five to six years to assess the rates of late side-effects. § Lancet Oncology rate of recurrence of breast cancer and the “The results suggest that a high total dose adverse effects associated with the different given in 25 small treatments is no better than iving a lower total dose of radiotherapy, approaches. simpler schedules, using fewer exposures to a Gdelivered in fewer, slightly higher-dose In the first study, the UK Standardisation of total dose,” said John Yarnold, chief investiga - treatments over a shorter period of time is as Breast Radiotherapy (START) Trial A, researchers tor for the two studies. “Shorter therapies giv - effective in reducing local relapses in women randomly allocated 2,236 women who had ing fewer, larger treatments are obviously with early breast cancer as standard radiother - undergone surgery for early breast cancer to convenient for patients. These results support apy of a higher total dose delivered over a receive the standard radiotherapy schedule the current use of shorter schedules in the UK longer time, and has no more side-effects, (50 Gy in 25 fractions of 2.0 Gy over five weeks), and in other countries,” he added. according to a large UK study. However, spe - or a lower total dose of 41.6 Gy (13 fractions of Other breast cancer specialists, however, cialists have cautioned that longer-term follow- 3.2 Gy over five weeks) or 39 Gy (13 fractions of have questioned the findings, arguing that up is needed to ensure that this radiotherapy 3.0 Gy over five weeks). After an average follow- increasing the radiation dose per fraction would regimen achieves a sustained reduction in the up of just over five years, the results showed that be expected to increase normal tissue damage risk of breast cancer relapse. the rate of locoregional tumour relapse in and reduce the therapeutic benefit. They point Radiotherapy after surgery for breast can - women given 41.6 Gy (3.5%) was similar to out that the results from the START trials cer has been shown to reduce local recurrence. that in women given 50 Gy (3.6%). However, it seemed to be contrary to those seen in studies This is important, as previous research has was slightly higher in women given the lowest in head and neck cancer, which show that shown that avoiding four local recurrences total radiotherapy dose of 39 Gy (5.2%). reducing the radiation dose per fraction at the saves one woman from dying of breast cancer. In the second study, START Trial B, a further same time as increasing the number of fractions The treatment is traditionally given in 25 daily 2,215 women with early breast cancer were (hyperfractionation) and the total dose leads to doses (called fractions) of 2.0 Gy, achieving a randomly allocated, following surgery, to the better tumour control and survival without total dose of 50 Gy over five weeks. However, standard radiotherapy schedule or a hypofrac - increased toxicity. Much longer follow-up is hospitals in the UK and Canada have been tionated schedule (40 Gy in 15 fractions of needed, they argue, to see if the apparently delivering a lower total dose in fewer, larger 2.67 Gy over three weeks). similar reduction in rate of relapse with fractions – termed hypofractionation – for Results showed similar rates of local- hypofractionated radiotherapy to standard some time, and retrospective studies have regional tumour relapse after five years: 3.3% of radiotherapy is maintained over time. shown that it appears to be as effective as women given standard radiotherapy and 2.2% standard radiotherapy in reducing the risk of of those given the hypofractionated regimen. A I The UK Standardisation of Breast Radiotherapy relapse, without increasing adverse events. significant reduction was also seen in the rate (START) Trial A of radiotherapy hypofractionation

46 I CANCER WORLD I JULY/AUGUST 2008 Impact Factor

for treatment of early breast cancer: a randomised surgery was 34 months compared to 28 months melanoma (MKP), while others have reported trial. The START Trialists’ Group. Lancet Oncol for those beginning therapy after six weeks. equivalent or better outcomes. The need for 4 April 2008, 9:331–341 Women who initiated treatment after six weeks clarification prompted Chris Lee and colleagues, had poorer overall survival ( P<0.0001) and ovar - from the John Wayne Cancer Institute in Santa I The UK Standardisation of Breast Radiotherapy ian cancer-specific survival ( P=0.009) than Monica, to review clinical records for 13,000 (START) Trial B of radiotherapy hypofractio- women who did not delay treatment. melanoma patients registered on a prospective nation for treatment of early breast cancer: a A second analysis, which looked at duration melanoma database between 1 April 1971 and randomised trial. The START Trialists’ Group. of treatment, showed that women treated for 31 December 2005. Lancet 29 March 2008, 371:1098–1107 three to seven months had 16% lower mortal - The study identified a subgroup of 1,571 ity than women treated less than three months. patients in the database managed with regional “Prospective studies of factors that influ - lymphadenectomy for palpable nodal metas - Delays in adjuvant ence the quality of care in women with OC tases within three months of presentation. Of [ovarian cancer] are needed,” write the these, 262 had MUP and 1,309 had MKP. For chemotherapy worsen authors, “but until such studies are com - each patient, age (whether they were under or ovarian cancer outcomes pleted, efforts should be made to facilitate over 60), sex, site of tumour involvement, § British Journal of Cancer prompt initiation and full completion of adju - number of tumour nodes, decade of diagnosis, vant chemotherapy.” status of primary (MUP or MKP) and clinical out - come were recorded. varian cancer patients who start I Variability in chemotherapy delivery for elderly Results show that five-year overall survival Ochemotherapy more than six weeks after women with advanced stage ovarian cancer and its was significantly better for the 262 patients debulking surgery and those receiving an impact on survival. JD Wright, T Doan, R McBride with MUP than for the 1,309 patients with abbreviated course of treatment are more et al. Br J Cancer 1 April 2008, 98:1197–1203 MKP (55% ±6% vs 44% ±3%, P=0.0021). Com - likely to die than those starting therapy within puterised matching of MUP and MKP by four six weeks and completing the full course of significant covariables (age, sex, nodal tumour treatment, according to an analysis of two Lymphadenectomy advised burden and decade of diagnosis) yielded 221 US cancer registries. matched pairs. Median and five-year overall Previous studies in ovarian cancer exam - for nodal metastasis survival rates were 165 months and 58% ±7% ining the time from surgery to initiation of from an unknown for MUP, compared with 34 months and 40% adjuvant chemotherapy have produced vary - primary melanoma ±7 % for MKP ( P=0.0006). ing results. A theoretical basis for the benefits The most likely explanation for MUP, say the of early administration of cytotoxic agents § Journal of Clinical Oncology authors, is that an unrecognised primary lesion was suggested by a mouse mammary tumour has undergone spontaneous regression medi - model, where removal of primary lesions verall survival is significantly better for ated by an endogenous immune response. “Our resulted in increased tumour proliferation. Opatients with melanomas of unknown pri - data strongly suggest that the initial treatment Dawn Hershman and colleagues, from the mary origin than for patients where the primary of MUP with nodal metastasis should be Herbert Irving Comprehensive Cancer Center, melanoma is of known origin, according to a regional lymphadenectomy,” they write, stress - used the US National Cancer Institute’s SEER recent US study. ing the importance of an accurate staging cancer registry and the linked Center for For 10%–20 % of patients presenting with work-up that includes complete imaging to Medicare and Medicaid Services (CMS) data palpable evidence of regional metastatic rule out distant disease. base to identify 6,047 women aged 65 years or melanoma, no primary lesion can be identified. “Unless the results of this work-up are pos - older with stages III–IV epithelial ovarian can - Proposed causes of unknown primary itive for metastasis beyond the regional basin, cer. A total of 3,585 women underwent surgery melanoma (MUP) include failure to recognise patients should undergo therapeutic (and and 2,558 (71%) received at least one cycle of the primary lesion during clinical examination, potentially curative) regional lymphadenec - chemotherapy. Of these, 1,712 (67%) started prior removal of the primary lesion during trau - tomy as the standard of care.” chemotherapy within six weeks of debulking matic injury or by excision without pathologic surgery, while 846 (33%) began treatment at diagnosis, and the unrecognised primary lesion I Improved survival after lymphadenectomy for least six weeks after debulking surgery. undergoing spontaneous regression. nodal metastasis from an unknown primary Results show the median survival for Some studies have reported poorer out - melanoma. C Lee, M Faries, L Wanek et al. J Clin women initiating treatment within six weeks of comes for MUP compared to known primary Oncol 1 February 2008, 26:535–541

CANCER WORLD I JULY/AUGUST 2008 I 47 Impact Factor

One in four do not decreased from 78% to 62%, while for those in been administered two cycles of induction adhere to aromatase the Market Scan it fell from 84% to 72%. Across chemotherapy with intravenous paclitaxel and all three data sets the proportion of women carboplatin, followed by concomitant weekly inhibitor prescription considered non-adherent ranged from 22% to intravenous paclitaxel and standard fractio- § Journal of Clinical Oncology 31% in year 1, rising to 32% to 50% in year 3. nation radiation therapy. For each subject, The results of the study have important formalin-fixed and paraffin-embedded biopsy round one-quarter of early-stage breast implications, say the investigators. “Patients who specimens were evaluated for the presence of A cancer patients taking the aromatase are non-adherent to adjuvant endocrine therapy HPV16 DNA by in situ hybridisation. inhibitor (AI) anastrozole do not adhere to treat - may be compromising their care. Oncologist Results show that, compared with patients ment, according to the largest study of adher - and patient awareness of the problem of non - with HPV-negative tumours, patients with HPV- ence to adjuvant endocrine therapy ever adherence, and communication regarding the positive tumours have a significantly better rate undertaken outside a clinical trial. The US study importance of adherence to therapy, may of response following induction chemotherapy suggests that a substantial proportion of improve health outcomes,” they write, adding (82% vs 55%; 95%CI 9.3% –44.7%, P=0.01), and women with early-stage breast cancer receive that future research should focus on identifying following chemoradiation treatment (84% vs suboptimal treatment. patients at risk for non-adherence and on devel - 57%; 95%CI 9.7%–44.3%, P=0.007). Further - In 2001 the ATAC study showed a statisti - oping interventions to improve adherence. more, patients with HPV-positive tumours cally significant improvement in disease-free showed an overall two-year survival of 95% survival for postmenopausal women taking ini - I Adherence to initial adjuvant anastrozole therapy compared with 62% for HPV-negative tumours tial anastrozole compared with initial tamoxifen among women with early-stage breast cancer. AH (95% CI 18.6%–47.4%, P=0.005). as adjuvant therapy for hormone-receptor- Partridge, A LaFountain, E Mayer et al. J Clin The association of tumour HPV status with positive early-breast cancer. Previous studies Oncol 1 February 2008, 26:556–562 survival and response to treatment, say the have suggested adherence to tamoxifen among authors, is sufficiently strong to warrant con - women with early stage breast cancer in the sideration in the design and analysis of future range of 25%–96%. This is important because, Better survival for HPV- head and neck cancer clinical trials. “Our data across all disease types, adherence has been suggest that the risks and benefits of intensive cited as the single most important modifiable positive squamous cell combined modality therapies should be factor compromising treatment outcomes. head and neck cancer considered separately for HPV-positive and In the present study, Ann Partridge and § JNCI -negative patients,” they write, adding that colleagues from the Dana-Farber Cancer Insti - failure to take such differences into considera - tute in Boston looked at whether similar pat - tion could lead to confounding results. terns of non-adherence occur in women atients with human papillomavirus- (HPV)- prescribed AIs for early-stage breast cancer. Ppositive head and neck squamous cell car - I Improved survival of patients with human The study focused on anastrozole, since it was cinoma (HNSCC) show better survival than papillomavirus-positive head and neck squamous the only AI approved for early-stage breast patients with HPV-negative tumours, according cell carcinoma in a prospective clinical trial. cancer during the study period. to a US study. The authors are calling for cancer C Fakhry, WH Westra et al. J Natl Cancer Inst Investigators used longitudinal claims staging systems to reflect these differences. 20 February 2008, 100:261–269 data from three large commercial US health Previous analyses of HNSCC tumours have programmes: Plan A, Plan B and the Market suggested HPV-positive oropharyngeal tumours Scan, which included information on 1,111 are clinically and molecularly distinct from HPV- No difference between women, 1,587 and 4,434 women respectively. negative tumours, and are associated with dif - For the purposes of the study, receiving med - ferent prognostic outcomes. In a prospective sequential and concomitant ication on less than 80% of days was defined multicentre study, Carole Fakhry and colleagues chemotherapy and hormonal as ‘non-adherence’. from the John Hopkins Medical Institutions in therapy in breast cancer Results show the number of days a patient Baltimore evaluated the association of tumour took anastrozole, known as the medication pos - HPV status with response to treatment and § Annals of Oncology session ratio (MPR), declined from year 1 to survival among 96 patients with stage III or IV year 3 of the study. For patients in Plan A, in HNSCC of the oropharynx or larynx. The subjects o difference in overall survival is evident year 1 the mean MPR was 86%, declining to – who were participants in an Eastern Cooper - Nbetween pre- and post-menopausal breast 79% in year 3. For those in plan B, mean MPR ative Oncology Group (ECOG) phase II trial – had cancer patients given sequential or concomitant

48 I CANCER WORLD I JULY/AUGUST 2008 Impact Factor

hormonal therapy with adjuvant chemotherapy, By 10 years, however, the survival rate had sexual activity. Less is known, however, about according to an Italian study. A slight advantage, fallen to 83% in the concomitant group (95%CI quality of life after brachytherapy and andro - however, was noted for concomitant treat - 78%–88%) and 80% (95%CI 74%–86%) in the gen-suppression therapy. ment in pre-menopausal patients. sequential group. Martin Sanda and colleagues from Harvard Adjuvant chemotherapy and hormonal The cumulative 10-year event-free survival University, in Boston, sought to identify deter - therapy are currently administered sequen - was 63% (95%CI 56%–70%) in the concomi - minants of health-related quality of life after pri - tially, with hormonal therapy following tant group and 54% (95%CI 42%–66%) in the mary treatment for prostate cancer and to chemotherapy. The study by Lucia Del Mastro sequential group ( P=0.570). determine how quality of life relates to overall and colleagues, from the Istituto Nazionale per In terms of overall survival, a significant satisfaction with the outcome of treatment for la Ricerca sul Cancro in Genova, set out to clar - decreasing trend in the hazard ratio for death or patients and their partners. Patients who under - ify optimum timing for treatments. A potential reoccurrence was observed with increasing age, went elected prostatectomy, brachytherapy or advantage of concomitant administration, indicating that concomitant therapy, as com - external-beam radiotherapy between March say the authors, is the possibility of avoiding pared with sequential therapy, might be more 2003 and March 2006 were enrolled in the detrimental effects of delaying tamoxifen. Pre - effective in younger patients. “A potential expla - study. In phone surveys, 1,201 patient and 626 clinical studies, however, have suggested neg - nation of this finding is that the early com - partners responded to questionnaires, including ative interactions between tamoxifen and mencement of tamoxifen could counterbalance the Expanded Prostate Cancer Index Composite chemotherapy when given concomitantly. So the bad prognosis reported in young pre - (EPIC-26) and Service Satisfaction Scale for far, randomised clinical trials have reported menopausal patients with ER-positive tumors CancerCare (SCA). Responses were obtained conflicting results: two trials found no differ - who are treated with chemotherapy alone,” before treatment and at 2, 6, 12, and 24 months ence between sequential and concomitant write the authors. The potential advantage of after starting treatment. treatment, while sequential therapy was found concomitant tamoxifen in young patients needs Results show adjuvant hormone therapy to be better in a third trial. The current study is to be further addressed in prospective trials, exacerbated the adverse effects of radiotherapy the first to include pre-menopausal women. they add. or brachytherapy, whereas nerve-sparing sur - The study retrospectively analysed out - gical procedures mitigated the adverse effects comes for 1,096 patients entered into two phase I Timing of adjuvant chemotherapy and of prostatectomy. Factors associated with worse III trials receiving adjuvant chemotherapy and tamoxifen in women with breast cancer: findings patient-reported outcomes were obesity, a tamoxifen either concomitantly or sequentially. from two consecutive trials of Gruppo Oncologico large prostate size, a high pretreatment In the MIG-1 study, patients had been ran - Nord-Ovest–Mammella Intergruppo (GONO- prostate-specific antigen (PSA) score, and older domly assigned to receive either six courses of MIG) Group. L Del Mastro, B Dozin, E Aitini age. At one year, 5% of partners reported being FEC21 (5-fluorouracil, epirubicin and cyclophos - et al. Ann Oncol February 2008, 19:299–307 bothered by the patient’s incontinence after phamide every 21 days) or six courses of dose- prostatectomy or brachytherapy, while 7% of dense FEC14 (same as FEC21 but given every 14 partners in the brachytherapy group and 3% days, with granulocyte colony-stimulating fac - Quality of life changes each in the radiotherapy and prostatectomy tor support). groups reported being bothered by the patient’s In the MIG-5 study, patients had been ran - in prostate cancer symptoms of urinary obstruction, such as uri - domly assigned to receive either the FEC21 § New England Journal of Medicine nary frequency. treatment or four courses of epirubicin and Black patients reported lower satisfaction paclitaxel every 21 days. In both trials, tamoxifen ach of the three common primary therapies with the degree of overall treatment outcomes was given either after completion of Efor prostate cancer – radical prostatectomy, than other patients. “We could not determine chemotherapy or concomitantly at the physi - brachytherapy and external beam radiotherapy whether these differences in outcome reflected cian’s discretion. – produce unique quality of life changes in disparities in the quality of care, in the expec - Of the total population of eligible patients patients relating to urinary symptoms, sexual tations of patients, or in cancer biology,” write from the two trials, 507 had received concomi - and bowel function, vitality and hormonal func - the authors, adding that further study will be tant tamoxifen and 589 sequential tamoxifen. tion, according to a recent American study. required to answer these questions. Results show no significant difference in Quality-of-life outcomes are important for overall survival between the two groups prostate cancer patients. Early studies review - I Quality of life and satisfaction with outcome (P=0.384). The cumulative overall survival at ing outcomes following prostatectomy or con - among prostate-cancer survivors. MG Sanda, five years was 94% (95%CI 92%–96%) in both ventional radiotherapy raised concerns about RL Dunn, J Michalski et al. N Engl J Med the concomitant and the sequential groups. urinary incontinence, bowel function and 20 March 2008, 358:1250–1261

CANCER WORLD I JULY/AUGUST 2008 I 49 Patient Voice Europe must tackle health illiteracy to avoid a health ‘underclass’

§ Peter McIntyre

A quarter of Europe’s citizens may miss out on better health, unless policy makers address functional illiteracy and improvements in the way information is presented.

he most shocking thing is that 20%–30% health system with low health literacy, they are again of Europeans in each and every society disadvantaged compared to other patients. The health - “ are functionally illiterate. They cannot care systems are not geared up towards responding to function adequately in our modern soci - patients with low health literacy. Professionals are not ety, and that means they cannot function even trained to recognise it.” aTdequately in a modern healthcare system. That is an Health literacy is firmly on the agenda of the new enormous challenge that our societies have to pick up.” EU Health Commissioner Androulla Vassiliou, who Ilona Kickbusch has been trying to put the concept had barely started in the job when she spoke alongside of health literacy onto the European agenda for more Kickbusch at the European Patients’ Forum (EPF) than three years – and it seems that she and her co- spring conference on health literacy in Brussels in thinkers are succeeding, even if many people still April. She warns that there is a danger of two classes find the term baffling and many European languages of citizens in Europe if some people lack the capacity do not even have a word for it. to describe symptoms, ask questions, evaluate health Kickbusch, former director of Health Promotion, information, analyse risks and navigate complex Education and Communication at the World Health healthcare systems. Organization and former Yale Professor of Global “Inadequate health literacy can result in little or no Health, sees health literacy as a core component of knowledge of medical care and medical conditions, inequality – a matter of life and death. decreased understanding of medical information, She defines health literacy as “the capacity to reduced use of preventive services, poorer self-reported make sound health decisions in the context of every - health, poorer compliance rate, poorer health status, day life – at home, in the community, at the work - increased hospitalisation, higher inequality and place, in the healthcare system, the market place and increased healthcare costs. the political arena”. “My belief is that within every member state we Those that that lack this ability are at a double dis - should have a set of patients’ rights and within the advantage. “We know that people who are less edu - patients’ rights should be reliable information to cated and are poorer already have a lower health patients especially from health professionals, especially status and life expectancy. Now when they enter the to understand whatever they are reading about

52 I CANCER WORLD I JULY/AUGUST 2008 Patient Voice

continent. The survey builds on work done by a team led by Jen Wang from the Insti - tute of Social and Preventive Medicine at the University of Zurich. His Swiss Health Literacy Survey, based on 30 measurable competencies, showed that 35% of Swiss people find choosing medication a highly complex process, and 34% say the same about treatment options. More than one in five regards choosing a doctor as a highly complex decision. But there is an appetite for involve - ment – 85% of patients want to participate in treatment decisions, while only 49% believe that they do so. Perhaps the most revealing finding concerns sources of information that people find easy to understand. While 94% of Swiss patients find information from their doctor ‘easy’ or ‘somewhat easy’, only 76–77% say this about the media, the Internet and patient information leaflets. Hardest to understand are food labels, regarded as ‘easy’ or ‘somewhat easy’ by only half the population. Y

M The survey put health literacy onto the A L

A agendas of the Swiss Federal Office of Public Health and other key bodies. In fact themselves and their particular illness or medicine.” Switzerland is one of only three countries in Europe Vassiliou points to a number of EU initiatives to (together with the UK and Ireland) to have any poli - improve information, including the EU Public Health cies on health literacy. “Outside the English-speaking Portal (http://ec.europa.eu/health-eu/) which pro - world, health literacy is not a very common topic in vides health information in 22 languages. (It is worth Europe yet,” said Wang. “The term for health literacy noting that this is a nicely laid out site, but hardly aimed may not even exist in your country.” at people with low health literacy. On the first cancer Levels of basic literacy vary widely between coun - page, the reader must understand “primary and sec - tries. In the figure overleaf, only those above the zero ondary prevention”, “a cancer surveillance system” and line (levels 3 or 4/5) meet the minimum OECD skills “the incidence of malignant neoplasm of the breast”.) to function in 21st century society. Those below the More to the point, perhaps, the EU Public Health line are struggling, while those in the bottom band ExecutiveAgency is putting money towards a Europe- are functionally illiterate. In Poland and Italy, this wide survey of health literacy that will create a network amounts to almost half the population, and in the UK, of organisations researching health literacy across the almost a quarter. In Norway, the Netherlands and “The healthcare systems are not geared up towards responding to patients with low health literacy”

CANCER WORLD I JULY/AUGUST 2008 I 53 Patient Voice

DOCUMENT LITERACY IN SELECTED COUNTRIES (16–65 YEARS)

This figure shows adult skills in deriving information from documents. Those above the zero line are considered to have ade - quate literacy skills to function in society. The yellow band consists of people who can derive information from written communica - tion only if it is very clear and simple (level 2). Level 1 is considered functional illiteracy. Source: International Adult Literacy Survey, 1993– 1997, Adult Literacy and Life Skill Survey, 2003

Germany, only 9%–10% are in this bottom band. garbage and it goes out from the body. I think health In research in Ireland, one in five people were not information is more or less the same. At the end you fully confident that they understand all the informa - need to reject unreliable information.” tion they receive from healthcare professionals.A full Hildrun Sundseth, from the European Cancer 60% did not fully understand the word ‘prognosis’ – a Patient Coalition, believes that patient advocates play term often used in patient consultations. a critical role in helping newly diagnosed patients Wang believes his research has the potential to deal with the information jungle. increase accountability and help bridge the gap She was diagnosed with melanoma 15 years ago between patient information and health education. and was very bruised by the experience. “I rung up my Whether the broader European research can achieve consultant and she gave me my diagnosis over the this is less certain. Although academic units in 16 phone two days before Christmas. I thought that was European countries have signed up, Wang has been my last Christmas. I was sitting there crying. given the money to carry out the research in only six. “After Christmas I went to see my GP and he said, He is looking for partners who can provide a further ‘I have someone on my patient list who has had the €1 million to make the research truly pan European. same condition as you for 20 years and she is still alive.’ That lifted me up.” PATIENT STORIES She says, “I feel sorry for doctors – they are human Much of the discussion about health literacy is about as well. But if you are giving information to patients, how health professionals and authorities can com - then you have to put the patient at the centre.” municate better with patients. But patient groups say that patients’ own stories can be the most helpful WHO GIVES INFORMATION ? in explaining choices and issues to new patients. There is a debate over who can best give information. Akiki Vrienniou from the Greek Multiple Sclero - Naturally enough, at the EPF conference, patient sis Society recalls how, despite being a university groups were the clear favourites for this role. graduate, she struggled to take in the impact of her Kickbusch says that health literacy implies a diagnosis. “When the doctor told me I had MS, I was choice about where to get information, and there is a totally confused because I did not know what this was need for a significant extra effort to reach the 20% with and how it would affect my life. There are a lot of ques - low literacy. Patient groups will be central to the tions and doctors do not have the time to answer all process. “There is a certain type of health literacy that these questions. They focus on the therapy.” only patients have. Without the experience of women She compares the mental process of using infor - with breast cancer, I guess they would still be cutting mation to make decisions with the physical process of our breasts off.” digestion. “The digestive system keeps the nutritious But while Vassiliou, the Health Commissioner, things for the body to function and the rest is just paid tribute to the work of patient groups, she also

54 I CANCER WORLD I JULY/AUGUST 2008 Patient Voice

“We are trying to create a dynamic doctor –patient relationship, based on dialogue and problem solving”

sounded a note of caution. “It is mainly the medical that patient at the right time and I don’t think any profession that can give this information, because doctor in the world is going to have that range of skills. they are the most qualified,” she told the EPF. “What “We are trying to create a much more dynamic is dangerous very often is that one patient gets infor - doctor–patient relationship, in which we get the con - mation from another patient, but his or her circum - cept of dialogue and problem solving, together with a stances might be very different. It is not very reliable joint plan; an agreement about how the doctor and to take for granted information from other patients. You patient go forward together in the interest of improv - have to corroborate the information you get from ing self-care and self-knowledge and improving trust health providers and physicians.” – a very precious commodity for both of us.” Strangely, perhaps, Michael Wilks, President of the One way in which he feels this could be done is Standing Committee of European Doctors (CPME), to ensure that the patient has the right to access their does not agree that doctors always know best. “We want own electronic records. “Large parts of the medical information that is understandable and relevant to profession have scepticism because they don’t want to lose control of that data. I think they need to be PLAIN TALKING FOR CLINICIANS reminded that it is not their data. The record may be in their computer, but the information actually The following list of user-friendly alternatives to common medical belongs to the patient.” terms was published by the American Medical Association Foundation There were also strong calls at the EPF conference and American Medical Association in a helpful manual for clinicians, to recognise the key roles of nurses and pharmacists Health literacy and patient safety: Help patients understand (2007), in the process of improving information to patients. which is available on the Internet. There is an ongoing debate about the role of the pharmaceutical industry in giving information. Cur - Analgesic Pain killer rently, patient information leaflets inside medicine Anti-inflammatory Lessens swelling and irritation packets are the most difficult of all information to read Benign Not cancer (because of the tiny type) and to understand (because Carcinoma Cancer of the language). Cardiac problem Heart problem Contraception Birth control HEALTH LITERACY INITIATIVES Enlarge Get bigger Health literacy initiatives in Europe are increasing rap - Heart failure Heart isn’t pumping well idly, even if they do not always use this language. The Hypertension High blood pressure growth of information services such as IQWiG in Infertility Can’t get pregnant Germany, La haute autorité de santé (HAS) in France Lateral Outside and NHS Direct in the UK reflects a growing desire Menopause Stopping periods, change of life to validate and disseminate clear accurate information. Menses Period In Ireland, the winners have just been announced Monitor Keep track of, keep an eye on in the first annual Crystal Clear Health Literacy Oral By mouth Awards, established by the National Adult Literary Referral Send you to another doctor Agency. A €1,000 award went to Ursula Courtney, Terminal Going to die Director of Services at the ARC Cancer Support Toxic Poisonous Centre, in Dublin, who established the ‘talk-together learn-together’ psycho-educative group for women with gynaecological cancers. Many described this as

CANCER WORLD I JULY/AUGUST 2008 I 55 Patient Voice

“I put all the papers in a closed envelope. I have not read any of them. I could not understand it”

their first real opportunity to talk about their fears and On the other hand, doctors have told them they do not thoughts about their cancer. have time to talk to the patients properly, let alone the Albert Jovell, who is a professor of Public Health family. “It is very difficult for us to communicate with and Preventative Medicine in Barcelona, is also a patients because the way we are trained to think is very cancer patient and President of the Spanish Patients’ complex. We follow organograms; we don’t follow Forum. He has been instrumental in starting a ‘patients the normal language people use.” university’ in Barcelona, billed as ‘a knowledge alliance The patient university has both a physical and vir - of patients and citizens’. Jovell talks about the crisis in tual presence. “We try to help patients and families the whole family, when a patient is diagnosed. “They navigate through the disease, like GPS navigation in feel paralysed. They have three diseases, not only the cars. We started what we call the ‘friendly hospital’. physical disease but the emotional and social aspects. Every time the cancer patient comes to the hospital, You have all these things we do not teach in a school there is someone who is going to take care of all the of medicine. You can find a lesson on pain, but you can - emotional and social aspects along the process. We say, not find a lesson on fear, ignorance or uncertainty.” don’t walk alone with the disease.” There is no lack of information, but a lack of guid - In the UK, a dozen pilots are taking place of an ance through it. One patient told them, “I put all the ‘information prescript ion’ to support patients. The papers in a closed envelope. I have not read any of Long Term Conditions Alliance, a grouping of 110 them. I could not understand it.” patient organisations, won support for this from all political parties before the last election. However, David Pink, chief executive of theAlliance, sees dan - gers as well as benefits in the term ‘health literacy’. “To Key recommendations some people it will tell us that the problem is in the The European Patients’ Forum made a number of recom - patient. Blaming the people served for the failings of mendations following its conference, including the following: the service is a real temptation.” He is also concerned about the possibility of mixed I More resources to extend the EU Health Literacy motives. “Some healthcare professionals want infor - Research Project across Europe mation prescriptions simply as a way of trying to get I A guide on how to make information user friendly patients to do as they are told, and patients are unlikely I Explore an EU ‘quality mark’ for health information to do as they are told as soon as they have access to the I EU funding for NGOs to translate information into full information. The Government’s support may well more languages be based on the hope and expectation that, with these I A right for patients to access and ‘own’ their electronic prescriptions, patients will go home and manage their health records own diseases and won’t demand so much from the I An EU programme to involve patient experts in training health services and that costs will be contained.” healthcare providers on good communication Whatever the motivation, however, there is a con - I Greater recognition of a patient rights agenda in pro - sensus emerging, and Pink is clear who should be lead - moting health literacy among marginalised groups ing it. “Patient organisations should be leading the I A clearing house for patient organisations, so they can discussions about health literacy in Europe. Patient adapt existing high-quality information groups understand the patient perspective, they are I Health literacy as part of a broader patients’ and citizens’ trusted by patients and they understand that health - information strategy across Europe care is something that must always be seen within the context of real lives of real people.”

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We’re back! How an alliance of patients and politicians put cancer back on the EU agenda

§ Anna Wagstaff

When Europe Against Cancer ended, the need for a Europe-wide strategy to tackle Europe’s growing cancer problem fell off the political agenda. Now, thanks to an impressive two-year campaign by patients and their parliamentary allies, key EU bodies are starting to give this issue the attention it deserves.

n afternoon of political Against Cancer. He was sponsoring a authorities before new legislation starts speeches in the Commit - comprehensive resolution due to go its journey through Parliament and tee of the Regions in before the Parliament on combating the Council. Brussels is not everyone’s cancer in the enlarged European Although the COR does not have cup of tea. Even Alojz Union. the power to veto legislation, it is PAeterle, founding chair of MEPs Marija Seljak was there represent - important because its members tend to Against Cancer and vintage political ing the Slovenian Minister of Health, be close to the delivery of services to campaigner, admitted that conferences Zofija Kukovi cˇ, who was about to make cancer patients. The COR was about like this ‘can be boring’. The April 7 –8 cancer the priority item at an informal to finalise its submission on the EU’s summit of the European Cancer meeting of all EU health ministers, draft health strategy Together for Patient Coalition (ECPC), however, under her chairmanship, in Brdo. Health: A Strategic Approach for the really wasn’t. Slovenia holds the Presidency of the EU 2008–2013. The top table brought together a EU for the first half of 2008. This was a perfect line-up to open combination of people who have the Androulla Vassiliou was present, a summit entitled Making Cancer a ability to make things happen for Euro - making her first public appearance as Priority, and testimony to three years of pean cancer patients. Not only were the newly appointed European Health intensive activity and nifty political they all singing to the same tune, but Commissioner. She is set to start footwork led by the European Cancer the tune sounded pleasingly similar to drawing up an EC Cancer Action Plan Patient Coalition and their political that composed by MEPs Against Can - for 2009. strike force, MEPs Against Cancer. cer when they put forward an action Also speaking was Luc Van den It signals a welcome return to plan for tackling cancer in Europe at Brande, president of the EU Com - focusing on cancer that had been all their first meeting, in 2006. mittee of the Regions, a ‘consultative’ but abandoned at European level after There was Georgs Andrejevs, one of body designed to bring in the expertise the ending of the Europe Against Can - the founding members of MEPs and opinions of local and regional cer programme in 2002.

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Patient power. Former ECPC president Stella Kyriakides asking the new N

Health Commissioner whether her Cancer Action Plan will be designed to A M E

act as a permanent lobby to pressurise governments to deliver. Seated to D L E

her left is Hildrun Sundseth, ECPC’s head of EU policy, and to her right Jan V E P P

Geissler, ECPC vice-president, and Sandy Craine, Secretary I L I H P

BUILDING POLITICAL WILL doned in favour of a health strategy But despite its termination, efforts Europe Against Cancer (1989–2002) that moved the focus away from tack - that began under the Europe Against was an initiative of the European ling specific diseases. Cancer programme continued to bear Commission that provided funding for Just as countries such as France, some fruit. In 2003, work conducted key areas of cancer control, including the UK and Denmark were beginning by the European Cancer Screening prevention, screening and cancer reg - to accept that cancer requires a strate - Networks generated an EC recom - istries. However, growing resistance gic, patient-centred, evidence-based, mendation on screening for breast, to EC ‘interference’ with national quality-controlled approach, the Euro - cervical and colorectal cancers. In the healthcare policies, pressure from pean Commission’s health directorate, same year, the European Parliament other disease groups, and the lack of a DG Sanco, redirected its efforts passed a resolution on the screening coherent European voice for cancer towards generic action to reduce smok - and management of breast cancer. led to the programme being aban - ing, improve diet and promote exercise. These measures have great potential, Only 7 countries have set up screening programmes for cervical cancer and only 11 for breast cancer

CANCER WORLD I JULY/AUGUST 2008 I 59 Systems& Services

ECPC and MEPs Against Cancer became an effective double act, building support among political leaders but their impact has been limited by on cancer as a good way to reconnect In November 2006, Slovenia hosted a lack of political will at European and the EU with its citizens – and he has summit on tackling cancer in the Member State level. Only seven coun - put an extraordinary effort into achiev - countries of central and eastern tries have so far set up cervical cancer ing this. Europe, which attracted politicians screening programmes and only 11 At its first full meeting early in and policy makers from across the provide nationwide screening for 2006, MEPs Against Cancer adopted region. An informal closed discussion breast cancer. The EC has yet to pub - a seven-point action plan that set at the start of the conference provided lish a progress report, due in 2006. out what it wanted from European a rare opportunity for political leaders and national political leaders (see to hold a high-level discussion of A VOICE FOR PATIENTS www.mepsagainstcancer.org). Top of strategies for cancer control in Europe. The formation of the European Can - its list of priorities was to Joaquim Gouveia, National Co- cer Patient Coalition in 2004 proved I Encourage member states to draw ordinator for Oncological Diseases in a turning point. Bringing together up and implement national can - Portugal, took back to his government more than 250 patient groups repre - cer plans a suggestion from the Summit that senting millions of survivors of many I End the socio-economic and geo - the issues of cancer registries, screen - different cancers, across 30 coun - graphic gap in cancer mortality ing and cancer plans should be singled tries, it has given Europe’s cancer I Convince the Commission to cre - out for a special discussion when Por - patients a single voice to fight for ate an EU cancer task force involv - tugal assumed the EU Presidency in their right to good care and social ing members of the Commission, the second half of 2007. inclusion, to argue for a role in policy the Parliament and the Council as A set of simple and clear recom - making, and to hold national and a forum to exchange information mendations on all three issues was European politicians to account. and to galvanise political will to agreed and are available in English ECPC searched out sympathetic translate policy into action (see figure opposite). politicians to champion the cause, and ECPC and MEPs Against Cancer To promote active surveillance of by the end of 2005, MEPs Against became an effective double act, mobil - the progress in cancer control across Cancer was launched under the co- ising patient advocates behind these Europe, they included in this docu - chairmanship of Adamos Adamou, Liz policies and building support among ment a set of maps and charts showing Lynne and Alojz Peterle. political leaders and policy makers. how Member States are performing in Peterle is himself a cancer survivor. They used the Eurocare-3 data to terms of registering cancer diagnoses, A former Prime Minister of Slovenia, show the difference that good preven - screening their citizens and operating he feels strongly the need to close the tion policies, effective screening and a cancer plan, which they intend to wide gap in cancer mortality between high-quality care can make to mortal - update in line with developments. ‘old Europe’ and the newer central and ity. They invited key players from the They also included in their recom - eastern European Member States. UK, France and Portugal to share mendations a provision that cancer Above all, perhaps, as one of the experiences of setting up national can - should be included as a standard item architects of the rejected European cer plans, and talked to patient advo - on the agenda of every meeting of EU constitution, Peterle is conscious of cates about putting pressure on health ministers. the dangerous distance between the political leaders to act to stem the This was taken up with enthusiasm structures of the European Union and increase in cancer cases in their own by Portugal’s successor to the EU Pres - the citizens of Europe – the so-called countries and to improve the experi - idency – Slovenia. In fact, the Sloven - ‘democratic deficit’. ence and life chances of those diag - ian government adopted cancer as the He sees delivering effective action nosed with cancer. main health focus of their term of

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Saints and sinners. This map, which can be viewed at www.acs.min-saude.pt/ Cancer control plans in Europe 2007/12/18/health-strategies-in- europe-workshop-sobre-cancro (go to Conclusões), shows how Member States are performing on cancer control plans. Similar data can be found at the same site for other key parameters such as population screening and cancer registries

office, which started in January 2008, and senior European policy makers were invited to a conference in Brdo in February, to take an in-depth look at strategies for reducing the burden of cancer in Europe. The Slovenian presidency also com - missioned a book, Responding to the challenge of cancer in Europe , which brings together current knowledge about the burden of cancer across the continent, and effective strategies for collecting data, carrying out popula - tion screening, organising high-quality care, and developing comprehensive strategies for control. A key chapter, contributed by Hil - drun Sundseth and Lynn Faulds Wood of ECPC, says that Europe has shown impetus and a European framework a lack of commitment to getting to for tackling inequalities and sharing grips with the growing cancer prob - best practice”. They also express hopes CLOSING THE GAP lem. “Astonishingly,” they write, “within that the Slovenian government would It’s still too early to make a full assess - the EU there seems to be little political use its presidency to “build the politi - ment of the Slovenian Presidency’s will to share and apply evenly the cal will required to force through the efforts, but the opening session of the knowledge we do have on how to pre - level of change and investment in ECPC summit in Brussels testified vent, diagnose and treat cancer, and health needed to close the gaps in to significant success in pushing can - how to care for patients…” cancer control, both within European cer high up on the agenda of every They reiterate the call for an EU countries and between the countries of part of the EU’s complex decision- cancer task force “to provide fresh east and west Europe.” making machinery. The ECPC summit in Brussels testified to significant success in pushing cancer high up on the agenda

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“Cancer patients have shown that working in partnership with political leaders can bring about change”

Luc Van den Brande of the Committee commissioner by his side in front of an summit that she had discussed this with of the Regions – “good fighters, who audience of cancer patient advocates, to Günter Verheugen, EC Commissioner feel the inequalities most,” according to stress his “sincere hope that this Task for Enterprise and Industry, saying that Peterle – said the COR Opinion on the Force will be established soon”. an effort should be made to make the EU’s draft Health Strategy 2008–2013 Maria Seljak, Director General of same types of medicines available in all prioritises action to reduce inequalities Public Health in Slovenia, told the EU countries, because these dispari - in health, since citizens “are exposed to summit that recommendations from ties cannot be maintained. “We are variable levels of health services, hos - February’s Brdo conference would be working towards it because we under - pitals and provision of qualified doc - discussed at the next meeting of the stand the inequity of this problem.” tors”. He promised, “The Committee of Social Policy, Health and Consumer She also recognises that the success the Regions fully supports all efforts in Affairs Council (EPSCO), in June, of the Cancer Action Plan for Europe helping to close the gap in cancer care which the Slovenian Minister of 2009 that she is charged with drawing in different regions of the EU.” Health would chair. up will depend on getting the plan The COR is pressing for stronger The emphasis will be on getting implemented in every Member State, mechanisms to encourage those with action throughout all Member States since healthcare is an issue of national day-to-day responsibility for organis - on the key priorities and strategies autonomy in the EU. “Certainly we ing and delivering healthcare at a agreed at the ministerial informal will put pressure on Member States, regional level to cooperate with one meeting. Slovenia would push the though we can’t force them. But if we another and exchange information, Council to recommend a comprehen - publicise the good practices of certain experiences and best practice. sive cancer control strategy across the states, we put other states in a difficult They are also pressing for health European Union. situation because they have to explain considerations to be taken into account To patient advocates, it certainly to their citizens why they don’t take the in developing EU policy on pharma - sounded as if their concerns are now same measures.” ceuticals. Their Opinion notes that the being taken seriously. And by a happy This, she says, is where patient health strategy currently fails to address twist of fate, this seems to have coin - advocates come in as partners for this issue, “despite the far reaching cided with the appointment of a real change, adding that any Cancer Task impact on patients and the public if the ally in the European Commission, in Force should include not only the provisions in place in this area are con - the person of Androulla Vassiliou. The Commission, Council and Parlia - sidered solely as a facet of industrial pol - Health Commissioner has a track ment, but also the involvement of icy and not in connection with health.” record on supporting cancer patients. patients themselves. Two days after the Patient Sum- She is one of the three founding As head of EU Policy for the mit the European Parliament adopted patrons of ECPC, and has long served ECPC, Hildrun Sundseth has been the 41-point cancer resolution as chairperson of the board of trustees co-orchestrator, together with Peterle, (http://tiny.cc/epcancerres). Crucially, of the Cyprus Oncology Centre. Faced of the two-year campaign to get cancer point 2 calls on the Commission to “set with searching questions from the floor, back on the EU agenda. She warmly up an interinstitutional EU Task Force she does seem geared up to confronting welcomed the new willingness to composed of Members from the Com - some of the obstacles in the way of get - tackle cancer more forcefully. “Can - mission, the Council and the Euro - ting action on cancer. cer patients have demonstrated that pean Parliament, which shall meet on a For instance, she does not accept working in partnership with political regular basis”. Canny politician that he that the EU can make policy about leaders and key players can bring about is, Georgs Andrejevs MEP grabbed the pharmaceuticals without reference to change. We’re looking forward to taking opportunity of having the new health the impact on patients. She told the that fight forward.”

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