EONS Magazine Autumn 2013 by European Oncology Nursing Society

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P A T I E N T

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Autumn 2013

Theme:

Rare Cancers Rare Cancers Europe: Joining forces for action

Researching rare cancers, challenges and solutions

EONS Lifetime Achievement Award: Professor Nurg端n Platin

Robert Schaefer

Jean-Yves Blay

Jim Boumelha

Contents Editor-in-Chief: Helen Oswald Executive Editor: Clair Watts Art Editor: Jason Harris Production Editor: Jim Boumelha

Autumn 2013

EDITORIAL 3 Learn from the rare Robert Schaefer

Editorial Assistants: Catherine Miller, Rudi Briké EONS Secretariat: Avenue Mounier 83, 1200 Brussels, Belgium Phone: +32 (0)2 779 99 23 Fax: +32 (0)2 779 99 37 e-mail: eons.secretariat@cancernurse.eu

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Reflections on nursing practice and rare cancers By Anita Margulies, our Board Editor for this issue Rare cancers in spite of not really being so rare are, on the whole, not widely discussed in nursing publications. Some articles, monographs for single tumour entities are retrievable, but in general this is unfortunately not a well-documented section of nursing care. Specialty nurses for rare cancers are equally rare. The numbers are reduced to single centres and usually only for one, or at the most two, disease entities. What happens with the rest? Where are our patients being treated? Are they being diagnosed and treated at all? What is generic for all rare cancers is the fact that they are often not recognised by nurses as rare, but rather just as another cancer. Rightly so, since these patients have the same wishes, questions, hopes as all other cancer patients.

What is particular for nurses to take note of, is the situation of probable late diagnosis and advanced disease already at first presentation in the clinic. Treatment for newly diagnosed disease is often initiated rapidly, with a hospital admission for surgical resection or immediate start of drugs. Although itâ&#x20AC;&#x2122;s the same for all cancers, it is essential with rare cancers that the nurse has an understanding of the tumour itself, the prognosis, new pharmaceutical therapies and a sound knowledge of the possible side effects and nursing management associated with these drugs. If the patient is to participate in a clinical trial, additional support will

be required if new drugs or procedures are to be implemented, and this will need to be addressed locally on behalf of the patient. Psychosocial implications must also be considered for all rare cancers, particularly as the prognosis is usually less favorable and complex treatment decisions can be overwhelming for both the patient and the caregivers. With increased awareness of rare cancers, oncology nurses can, with early intervention, provide support to improve the quality of life through correct information and realistic care models for patients and their families. We hope this issue of EONS magazine is helpful in this respect.

An introduction from the new EONS Magazine Editor-in-Chief, Helen Oswald I hope you are enjoying this latest issue of the EONS magazine, on rare cancers. Since the last issue there have been a few developments in the team producing the magazine and I would like to introduce myself as the new Editor-in-Chief. First a little bit of history. You may be aware that in 2009, the EONS magazine was re-launched under the direction of the Executive Director, Clair Watts. A new editorial team was brought together and delivered a fresh design and format. Four editions per year were produced, with specialist themes including Prostate Cancer, Education and European Healthcare Policy.

As the magazine went from strength to strength, it became clear that the role of Editorin-Chief would increasingly require a significant time commitment and so the position was advertised. I was appointed to this role in July this year, with Clair remaining at the helm as Executive Editor. The rest of the magazine team remains broadly the same. A few words about me: I am a graduate of London University and also hold an MA in Creative Writing from the University of East Anglia. I trained as a professional journalist and began my career in print media. As my career as a writer and editor developed, I worked with a variety of membership organisations in the public, charity and trade union sectors - from

Amnesty International to Unison and the National Union of Journalists. I have a lot of experience producing membership publications in a number of fields and I very much look forward to working with the EONS community to help make the magazine the very best it can be. This edition, on the theme of â&#x20AC;&#x2DC;rare cancersâ&#x20AC;&#x2122;, coincides with the European Cancer Congress in Amsterdam. The next will take as its theme the Congress itself. It will report on the latest research and educational developments in oncology nursing and be available early next year. The magazine very much welcomes suggestions for themes and content. Please email me with your ideas and comments at eons.magazine@ cancernurse.eu. Finally, a big thank you to all our contributors to this issue.

Executive Board Elections 2013 A warm welcome from President Birgitte Grube Following our recent elections, I am delighted to welcome four new Executive Board members: Daniel Kelly (UK) as President-Elect, Patrick Crombez (Belgium) as Executive Board Member – Advocacy and Andreas Charalambous (Cyprus) as Executive Board Member – Education. Maria Cristina Correia de Lacerda (Portugal) has been elected as our new Treasurer. As President and on behalf of the EONS Executive team and EONS Board, I wholeheartedly congratulate all four new Board members. I would also like to thank all the candidates for their enthusiasm and interest in engaging with EONS. Thank you also to everyone who voted for actively engaging with the work of EONS, your Society. All the results now move forward to the General Meeting for member approval at the European Cancer Congress (ECC), Amsterdam, The Netherlands, on Sunday 29 September at 18.30. And finally, a few words to welcome our new President, Erik van Muilekom MANP, to whom I hand over the role at the ECC. Erik started his nursing career in 1987. He specialised in oncology and became a staff nurse at a surgical ward for abdominal surgery at the Netherlands Cancer Instituut-Antoni van Leeuwenhoek hospital in Amsterdam. He became a clinical nurse specialist in 2001 and finished his masters degree in Advanced Nursing Practice in 2007. Besides his cliniErik van cal work he has been Muilekom a board member and

treasurer of the Dutch Oncology Nursing Society and chair of the national annual congress for oncology nurses. He is also president of his own foundation to promote expertise in oncology/urological nursing care in the Netherlands. In 2007, he received the prof. dr. Muntendam Award from the Dutch Cancer Society for his contribution to promoting expertise in oncology care and patient education. I wish you all the very best for your time as EONS President, Erik. President-Elect – Daniel Kelly Danny is from the United Kingdom and has been a member of the EONS Board for six years. He has over 30 years’ experience as a cancer nurse, educator, manager and researcher. He will bring continuity to the Board and provide experience and insight into the challenges faced by EONS in the present financial climate, as he has previous experience as Treasurer. Education – Andreas Charalambous Andreas is from Limassol, Cyprus, and is President of the Cyprus Oncology Nursing Society. He has been a member of the EONS Research Working Group and has a long-standing career in cancer nursing practice, education and research on a local, national and international level. He will benefit the EONS strategic plan to develop and review educational programmes. Andreas will also work towards the development of a culturally competent educational programme

Birgitte Grube

that is driven by evidence-based knowledge and is accessible to every member of EONS. Treasurer – Maria Cristina Correia de Lacerda Cristina has been a nurse for 27 years. She is the President of the Portuguese Association for Oncology Nursing (AEOP) and has experience at the highest level in nursing practice, management, education and policy. She aims to use her experience as a nurse to achieve the vision, mission and the strategy plans of EONS with the funding needed. Cristina seeks to develop and promote excellence in cancer nursing practice across the different countries of Europe, adapting and helping to develop new strategies if necessary. Advocacy – Patrick Crombez Patrick is from Belgium and is head nurse at the Department of Haematology and Stem Cell Transplantation at the J. Bordet Institute in Brussels. Patrick has been an individual member of EONS a long time. With his leadership skills and knowledge gained from working in different societies he would like to be be actively involved in policy matters contributing to the development of coherent European policies in cooperation with other European organisations and cancer nurse leaders.

Show your support and sign the Call to Action Against Rare Cancers:

www.rarecancerseurope.org

Learn from the Rare! » Nature is nowhere accustomed more openly to display her secret

mysteries than in cases where she shows traces of her workings apart from the beaten path; nor is there any better way to advance the proper practice of medicine than to give our minds to the discovery of the usual law of nature, by the careful investigation of cases (William Harvey, M.D., 24 April 1657*) of rarer forms of disease.

» The corollary to our hypothesis is the prediction that new thera-

pies will continue to show their most salutary effects in rare cancers. Furthermore, only by stratifying the common tumors, especially when using targeted agents, into the molecular subsets of diseases that compose them are we likely to achieve a substantial effect in these (Fadi Braiteh, M.D., Razelle Kurzrock, M.D., 12 April 2007**) disorders.

To find out more about the added value of research on rare cancers and about Rare Cancers Europe, visit www.rarecancerseurope.org. * Willis R. The works of William Harvey, M.D..1847;616-617. ** Braiteh F., Kurzrock, R. Uncommon tumors and exceptional therapies: paradox or paradigm? Mol Cancer Ther 2007;6:1175-1179.

Rare Cancers Europe: Joining forces for action Robert Schaefer describes the journey that led to a unique multi-stakeholder initiative to address the key challenges linked to rare cancer research, treatment and care in Europe.

The story begins in November 2008 in Brussels, with the conference “Rare Tumours in Europe: Challenges and Solutions” marking the beginning of the Rare Cancers Europe (RCE) partnership initiative. The conference was hosted by the European Society for Medical Oncology (ESMO) and organised in partnership with several stakeholders active in the fields of rare diseases and cancer. It offered an opportunity for EU policy-makers and regulators to meet with cancer researchers, healthcare professionals, rare disease and rare cancer patients and patient advocates, government representatives and the pharmaceu-

tical industry to discuss ways to address the key challenges linked to rare cancer research, treatment and care in Europe. The conference participants publicly called for awareness and prioritisation of rare cancers and agreed on 39 political and stakeholder recommendations, addressing: ●● regulatory barriers in rare cancer care ●● methodological barriers to rare cancer care ●● the need for centres of expertise and European reference networks ●● barriers to patients’ access to care ●● the education of healthcare professionals ●● access to information on rare cancers.

A CALL TO ACTION Based on these recommendations, the partners involved in the conference launched a public “Call to Action Against Rare Cancers” (which you can sign at www.rarecancerseurope.org). This calls on European governments, the European Union institutions and other international governmental organisations, the research community, the pharmaceutical industry, medical professionals and members of civil society to give a high priority to addressing the specific challenges associated with rare cancers. It wants to see all work towards: ●● substantially improved equity of rare cancer care across borders

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●● the

development of new effective therapies for rare cancers ●● facilitating more clinical studies in rare cancers with greater flexibility ●● balanced, timely and transparent assessment of new therapies ●● building a knowledge-base through clinical database networks, rare cancer registries and tissue banks ●● increased knowledge-sharing across borders through centres of expertise and reference networks ●● timely and accurate detection and provision of care through appropriate referral of patients to centres of expertise and reference networks. The “Call to Action” and the 39 recommendations both build the framework for the ongoing activities of the RCE multi-stakeholder initiative, which aims to place the issue of rare cancers firmly on the European policy agenda and advocate for the implementation of the recommendations. By summarising these recommendations under the following overarching goals, the initiative has agreed on a series of meaningful and manageable joint projects and activities: 1. To improve the methodology of clinical research on rare cancers. 2. To improve the organisation of health care in rare cancers. 3. To improve access of rare cancer patients to new therapies in the EU. REACHING A CONSENSUS The first activity under goal 1, is to reach a multi-stakeholder consensus on ways to improve the methodology of clinical studies in rare cancers, focusing on the following aspects: design of clinical studies, end-points of clinical studies, methods for combining available evidence, and organisational and regulatory aspects of clinical studies. To facilitate this process, an online consensus discussion has been set up, involving various stakeholders, to develop a consensus document. A follow-up consensus meeting and a related Rare Cancers Conference in Brussels were organised by ESMO and RCE in early February 2012. The consensus

discussion is still ongoing, and once a final agreement is reached and the consensus paper published, a targeted advocacy campaign will encourage the swift implementation of the proposed recommendations and action steps. Projects related to goal 2 include an exemplary survey on existing clinical practice guidelines for selected rare cancers. The survey will enable us to better understand the reasons for discrepancies and explore the potential for harmonisation of those guidelines across Europe to ensure optimal care for rare cancer patients. This will be done in close coordination with related activities carried out by the European Partnership for Action Against Cancer (EPAAC). In addition, consensus guidelines for quality criteria of collaborative networks in rare cancers will be developed.

action both at EU and national level. Activities on behalf of goal 3 include a series of comparative text and video case studies on haematological and childhood cancers. These aim to illustrate key issues and opportunities in the rare cancers arena concerning access to treatment and care within the EU. Since its inception in 2008, the RCE multi-stakeholder initiative has grown from 12 founding partners to 32 cooperating organisations. The campaign is moreover supported by additional corporate supporters. For more information, please visit www. rarecancerseurope.org. Together we can ensure that policy-makers and all other relevant stakeholders give high priority to quality treatment and care for patients with rare cancers.

Caption: Picture on the facing page shows the Rare Cancers Europe (RCE) partnership meeting, Stockholm, 23 September 2011. Standing (from left to right): Jan Geissler (Chronic Myeloid Leukaemia Advocates Network), Susanna Leto di Priolo (Novartis Oncology Region Europe), Gracemarie Bricalli (European Society for Medical Oncology, ESMO), Anita Margulies (European Oncology Nursing Society, EONS), Antoni Gelonch Viladegut (Sanofi), Alan J. Howard (ESMO), Prof. Dr. Gilles Vassal (European Society for Paediatric Oncology,

Rare Cancers Europe will also provide input to the new EU Commission-funded three-year RARECARENet project, which aims to identify clinical centres of expertise for rare cancers and establish a related information network across Europe. In collaboration with ESMO, the project also envisions the development of additional clinical practice guidelines on rare cancers currently not addressed. In collaboration with the European Society of Pathology (ESP), RCE and ESMO are organising a consensus meeting in autumn 2013 focussing on the issues around the pathologic diagnosis of rare cancers. Pathology is one of the most significant aspects for the accurate diagnosis of rare cancers. This meeting will provide an opportunity for identifying the existing challenges, as well as enabling stakeholders to put forward recommendations for

SIOP Europe), Prof. Dr. Paolo G. Casali (ESMO and Fondazione IRCCS Istituto Nazionale dei Tumori, Conticanet, EuroBoNeT and World Sarcoma Network, WSN), John Bean (European Organisation for Research and Treatment of Cancer, EORTC), Prof. Dr. Ruth Ladenstein (SIOP Europe), Dr. Clair Watts (EONS), Kathy Oliver (International Brain Tumour Alliance, IBTA and Cancer 52). Seated (from left to right): Edel Fitzgerald (SIOP Europe), Christina Claussen (Pfizer Oncology), Prof. Dr. Nicholas Pavlidis (European School of Oncology, ESO), Robert Schaefer (Rare Cancers Europe). Not all the RCE partner organisations are represented in this photograph. You can find the full list of partners at www.rarecancerseurope.org For information on Rare Cancers Europe (RCE), please contact: Francesca Longo, Patient Affairs Officer, ESMO Patient Affairs and RCE Secretariat, francesca.longo@esmo.org.

Professor Nurgün Platin “An ember burns where it falls” The transformation of nursing into a skilled professional career has happened thanks to leaders in nursing education. Professor Nurgün Platin pioneered the Oncology Nursing Association in Turkey and dedicated many years to the education of oncology nurses. Last year, EONS presented her with a Lifetime Achievement Award.

or somebody who has pioneered the educational activities of cancer nurses and has taught successive nursing student generations for more than 30 years, Professor Platin is remarkably self-effacing. Summing up what had motivated her to take on the task of helping develop nurses’ thoughts and shape their education, she said, “I did not have any motto to start with. But what I have observed, heard and felt led me the way. Maybe it was an action-led process. I had no teachers or icons to identify with. But my life philosophy is to compete with my own self.” Professor Platin had the right tools for the job. Starting with a BS, MS and PhD degrees in nursing, she held over the years numerous teaching posts in universities, in particular the Hacettepe University School of Nursing in Ankara, and in various hospitals. Her initial expertise was in paediatric nursing, but her professional interests moved over time to the area of a theoretical framework of nursing which she still teaches at graduate level, and oncology nursing, in which she still contributes in practical settings. But what fed her early commitment was not necessarily her move into academia, so much as observing the difficulties patients faced in hospitals and healthcare settings, and the need to improve nurses’ understanding of these difficulties and their ability to address them. She takes as a starting point a Turkish proverb “an ember burns where it falls” to underscore the need for empathy in

daily life events. “Nurses need to develop their self-confidence,” she argues with passion, “they need to be motivated, to get over the burnout in nursing, to develop a network among oncology or chemotherapy nurses and have a strong association behind them, they need to be a part of a community. And, most importantly, nurses must be ready for change and improvement.” Understanding needs and providing care to meet those needs are directly connected to the issue of self-confidence, says Professor Platin, who is highly aware of how difficult oncology can be. Her advice to student nurses is to confront it head-on. “We are to accomplish the difficult. We are unique and being unique brings in some responsibilities and challenges. Now we are dealing with those challenges and responsibilities.” Every day she tries to galvanise them into seeing and believing in their own potential. For those on their first assignment, her advice is, “Think that this is your first step to becoming a great nurse of the future, you are there to learn, and there are a lot of things that

will support you to achieve nurses’ great mission. Be confident, listen to what the patient says, search for answers, ask questions, write down what you have learned or seen, share your questions and notes with your instructor.” A common collective vision is necessary to mould student nurses into a team and it can be achieved despite the competitive nature of the courses. “Sometimes personal and professional visions can converge if nurses join and see where they stand with each other. It is then that they hear about achievement stories. This can motivate them to work with others or to contribute to bigger ideas,” she argues. Professor Platin is keen to nurture student nurses, in particular her doctorate and MS students. She has been encouraging them to try and channel any performance or idea towards producing something, such as writing an article about it or presenting it somewhere, or introducing them to some other groups to join, or working to expand the idea. She worries, however, about the potential for burnout among excellent clinical nurses “who have massive experience in conflict resolution, observation, problem solving and intuition in many areas,” particularly if they get no recognition or opportunities for promotion. She suggests they should be used as source persons or consultants for clinical problems so they can share their heritage while they are still in the profession. Professor Platin’s lifetime involvement in nursing education took her into other roles as she got involved with various national associations, institutions, and commissions related to nursing and health services. This colossal work was recognised in 1999 when she received a science award from Istanbul University Florence Nightingale School. She has also taken part in numerous EU projects, and worked as an active member both in the Oncology Nursing Association in Turkey and in the European Oncology Nursing Society (EONS). Recalling her many responsibilities with her national association, she says, “I did achieve the things that I thought were important”. She mentions as a

JASON HARRIS

INTERVIEW

highlight that when she held the presidency of her association, she took up the issue of protective clothing for nurses preparing chemotherapy and her work had a huge impact in Turkey, and undoubtedly protected many cancer nurses from harm. “But, however,” she says “there is so much more to do. Now there is a big group of nurses, both academic and clinical, who are members and lots of younger nurses are eager to work with oncology patients and do their thesis in the area.” Professor Platin takes every opportunity to remind her students to be accessible and engaged at all times, constantly pressing them to “keep the communications channels open, work together, use connection networks.” And she unremittingly uses her lifelong experience of “meetings, workshops, inviting experts from other countries and listening to their accomplishments, seeing their efforts and taking them as role models” to instill in her students a sense of how best they should get their colleagues involved and feel that their input is important, necessary and unique. Described by one of the leaders of EONS as the “spirit of nursing” in Turkey, does she see herself as a role model? “I don’t know if I am the spirit of nursing,” she replies, “but I think I know and understand what nursing is. And I like to share that with other people, to enjoy and be proud of their profession. Some people say that I am their role model.”

Peer recogniton. Nurgün Platin receives her Lifetime Achievement Award from EONS President Birgitte Grube at the EONS 8 Congress, Geneva, 2012

The role and support of caregivers: We also ride the brain tumour roller coaster Kathy Oliver, Founding Co-Director of the International Brain Tumour Alliance (IBTA), whose son Colin died from a brain tumour in 2011, describes the important role of the caregiver. She charts the journey from diagnosis to ‘living the new normal’, to coping strategies for caregivers and the lessons that can be learned along this challenging path.

“It’s like standing on the shore watching him out at sea. Sometimes the waves bring him back closer to me and sometimes the tide takes him away again.” These words, written by a caregiver, hauntingly capture the emotional ups and downs of looking after a person with a malignant brain tumour. Brimming with pathos, tinged with strain, and symbolic of a journey that is unique in the atlas of diseases, these two simple sentences highlight the fact that caregivers also ride the brain tumour roller coaster. One of the most striking things about brain tumours is that, unlike other cancers, they intersect three major disease areas: cancer, neurological disease, and rare disease. This triumvirate presents a huge challenge to both the patient and the caregiver.

Understanding the Caregiver’s Perspective The stresses resulting from a brain tumour diagnosis are significant and fairly well-documented for patients. But the effects of this devastating diagnosis on the caregiver were historically not so widely understood or recognised. In recent years, however, there have been a number of studies focussing on the brain tumour caregiver’s role, especially with regard to high-grade glioma. A team from the Department of Oncology at the University Hospitals in Leuven, Belgium, led by Wendy Sterckx, carried out a systematic review from the patient’s and caregiver’s perspectives on the impact of a high-grade glioma on everyday life. The results were published in the European Journal of Oncology in 2012.1

The review states: “Caregivers associate the diagnosis [of a brain tumour] with a loss of safety in daily life. Suffering and powerlessness loom large ... Feelings of being overwhelmed, denial, anger and isolation are described. In an attempt to cope with the diagnosis, caregivers take every day as it comes and do not want to plan ahead. They try to prepare themselves for the worst and want to be ready for when the patient deteriorates.” This same Leuven review mentions that the patient’s cognitive and neuropsychiatric symptoms are the greatest challenges for caregivers. Furthermore, the paper quotes other studies – notably Fox and Lantz, Sherwood et al, Janda et al, and Schubart et al – when it reports: “[A brain tumour] is a family disease. Caregivers’ distress

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is reflected in burden and depressive symptoms, both related to the reduced independence and neuro-psychiatric symptoms of the patient. Compared with caregivers of other brain tumour patients, caregivers of patients with a glioblastoma have a worse quality of life and may have more psychosocial needs because the disease process is faster and they have less time to adapt.” A 2010 Australian study of highgrade glioma brain tumour caregivers from a team in Perth pointed out that: “... Caregivers in this study reported experiences similar to those described by caregivers of people with other cancers. What differed for this group [of brain tumour caregivers] was the rapidity of change and the need for immediate information and support to assist with caring for a person with high grade glioma.” 2 Living the New Normal After diagnosis, brain tumour patients and their caregivers must try to rebuild their lives and learn to live the “new normal”. For the caregiver this may include a major readjustment in family dynamics and roles. Caregivers may have to learn how to move and handle a patient, organise equipment, monitor and administer medications, become the family’s main transport person, oversee the patient’s personal care, and help the patient cope with treatment side effects. Caregiving can be incredibly intense and extremely isolating. On the other hand, many caregivers have also said that the inspiration and courage shown by the brain tumour patient may bring them to a new level of deep love, admiration, and closeness with the patient. Time together is cherished in a way that it has never been before.

Kathy Oliver with her husband Gordon, daughter Miranda and son, Colin.

Caregivers and the IBTA Survey The International Brain Tumour Alliance (IBTA) carried out a patient and caregiver satisfaction survey in 2010 which asked: “Was information about your diagnosis and prognosis provided to you in a considerate and sensitive manner and in a suitable physical environment?” 3 Although 59% of those surveyed responded “yes”, a number highlighted less than satisfactory situations. They included a lack of compassion shown by medical staff, bad news being broken in inappropriate surroundings, and a nihilistic attitude on the part of doctors.

University Medical Center in Amsterdam says: “Research to date indicates that, while continuing to face significant caregiving stress, caregivers can benefit greatly from structured psychosocial interventions, leading to clinically significant improvements in the caregiver’s quality of life.” We at the IBTA have seen that it may be useful for families, if they wish, to be paired in a buddy system with other families on the same journey so there is peer-to-peer support. This is something that brain tumour patient support groups often facilitate. But unfortunately, not all families are put in touch

“Research to date indicates that, while continuing to face significant caregiving stress, caregivers can benefit greatly from structured psychosocial interventions, leading to clinically significant improvements in the caregiver’s quality of life.”

One respondent wrote: “We did not understand the terminal prognosis, it was not properly explained ... [This was] harmful to the surviving partner as expectations were not properly set. The surviving partner is a ‘patient’ in this sense also, but is not treated as such. I think there is a need for counselling being given to the partner-carer in parallel with the treatment for the patient.” Helping Caregivers Cope So what can caregivers do to help themselves cope on this journey? Information, befriending, and support for caregivers is available from brain tumour charities. However, not every country is fortunate enough to have these organisations. A directory of brain tumour charities known to the IBTA is available at www.theibta.org/ websitelinks.html A 2012 article in Brain Tumour magazine by Dr Martin Klein of the VU

with these groups by clinicians at the time of diagnosis. Some neuro-oncology departments run their own support group meetings which facilitate such introductions. In many cases, it is the specialist neuro-oncology nurses who run these groups. Klein also mentions the use of “... E-Communities by which caregivers are connected to their peers ... over the Internet.” There are, in fact, a number of highly regarded, reliable web resources for brain tumour caregivers. Used by patients and caregivers worldwide, the US-based Musella Foundation’s website – www.virtualtrials.com – houses a section on survivors’ stories which can help give people hope. The website also hosts a number of excellent online discussion groups where patients and caregivers can find information, support, friendship, and understanding.

The Cancer Institute New South Wales (Australia) website features an excellent set of 16 brain tumour fact sheets and 11 resource sheets. These cover topics such as anger management, stress, concentration, communication, and fatigue, and are not just aimed at the brain tumour patient but at the caregiver as well. Lessons Learned There is no exact science to caregiving. It seems to hover somewhere between treading on eggshells, juggling dozens of balls at once, and having unlimited reservoirs of physical and mental strength. As one of the caregivers to our son Colin for over seven years, until he died in August 2011 from his brain tumour, I learned many lessons. I learned that caregiving must be a partnership so that the patient can make his or her own decisions and choices as much as possible in order to feel that they are still in control. I learned that it is also vital not to forget the needs of other people in the family; to accept help from relatives, friends, and neighbours when they offer it; to maintain continuity and as much of a sense of normality as possible. Finally, I learned that the hope and encouragement you give as a caregiver to the patient can go a long way in helping alleviate some of the nightmarish aspects of the brain tumour journey. As Dr Jerome Groopman, a leading cancer researcher, said: “Hope acknowledges the significant obstacles and deep pitfalls along that path. True hope has no room for delusion. … Hope gives us the courage to confront our circumstances and the capacity to surmount them.” 4

Details of the references cited in this article can be accessed at www.cancernurse.eu/magazine Reprinted with kind permission of the European Association of NeuroOncology Magazine: EUR ASSOC NEUROONCOL MAG 2013; 3 (1): 31–2 [http://www.kup.at/eano].

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Equipping nurses with the skills they need Katarina Lokar, of the Institute of Oncology Ljubljana, Slovenia, provides a first-hand insight into the development of a national specialisation programme in cancer nursing in Slovenia, and how EONS resources have contributed.

The burden of cancer is growing and becoming the number one healthcare problem in Slovenia, as elsewhere. In order to manage the problem of cancer the National Cancer Control Programme was developed (NCCP). Its purpose is to reduce the number of new patients, increase survival, increase the importance of prevention, improve organisation of cancer healthcare services. One of the purposes of NCCP is also to improve the education of healthcare professionals. Last year, as part of the project that relates to the education of healthcare professionals, the National Specialisation Programme in Cancer Nursing was developed. The intention is to provide each person affected by cancer with quality needs-oriented care at all levels of cancer nursing care (primary, secondary and tertiary), thereby improving disease out-

comes and care. The aim of specialisation is to equip nurses who work daily with cancer patients and their families with additional knowledge, competencies and skills in the field of cancer nursing. As is usually the case in such matters, we asked ourselves where to start. We needed to develop a contemporary programme that will cover many different requirements. We got our answer in the EONS Post-basic Curriculum in Cancer Nursing. For us, it was a very good foundation for the programme and also offered us enough flexibility for adaptation to the national healthcare and educational systems. The result of our work is the National Specialisation in Cancer Nursing: it takes one year, a total of 1,800 hours (60 ECTS). It includes theoretical content, practical training, and individual student work. Since specialisation is primarily intended for acquisition of clinical skills and competencies, the emphasis is on practical training in a clini-

Left to right: Katarina Lokar with colleagues Miladinka Matkovic and Marjana Bernot who were also involved in

cal setting. It was also very important to us that nurses would be able to understand the experiences of people affected by cancer. That is why we designed the programme in such a way that a nurse follows the path of the patient through the healthcare system, so that s/he is getting the whole picture not just part of the patient’s journey. The specialisation programme incorporates mandatory theoretical and practical modules that equip nurses with basic knowledge about cancer and cancer nursing care of patients. They are followed by elective modules which are primarily aimed at the acquisition of specialised competencies to cover nurses’ areas of work, for example, modules covering palliative care, paediatric cancers, hemato-oncology, etc. Through the elective part of the programme we were also able to develop a breast cancer nursing module – something we were trying to do for years. As a country with a population of two million we need only a small number of breast cancer nurses and had not been able to provide a sustainable educational programme. The fact is, if we want to have breast cancer centres according to the EUSOMA guidelines, we need breast cancer nurses. We now have a solution: we designed a breast cancer nursing module based upon EONS Post-basic Curriculum for Breast Cancer Nursing and the EUSOMA guidelines. Now, the real challenge for us will be to get funding for the new specialisation in these times of economic crisis.

developing the programme. Katarina is Assistant Medical Director for Nursing and Care at the Institute of Oncology Ljubljana, Slovenia. She is a member of EONS’ Advocacy Working Group.

Rare â&#x20AC;&#x201C; but more common and more challenging than Taken together, rare cancers account for a relatively high proportion of all cancers. Though a diverse group of diseases, they present common problems due to their low frequency and the limited expertise available.

Annalisa Trama, Roberto Mazza and Gemma Gatta

MIC SMITH PHOTOGRAPHY LLC / ALAMY

our cancers dominate the overall cancer burden profile throughout Europe: breast, prostate, colorectal and lung. Many more types of cancer appear only rarely including gliomas, sarcomas, neuroendocrine tumours, tumours of the nasal cavity and sinuses or tumours of the trachea. These rare cancers, taken together, affect one in every five cancer patients and yet they receive far less attention. How many doctors have ever diagnosed/ treated one of these tumours and how many oncology nurses have ever seen patients with such tumours? Probably very few because these cancers are rare and therefore very infrequently diagnosed. In the 27 countries that make up the European Union, breast cancers account for 320,000 new cases, and colorectal cancers 300,000 new cases, as compared to the 26,000 for gliomas, 12,600 for neuroendocrine tumours (excluding those of the lung), 2200 for tumours of the nasal cavity and sinuses and only 700 for tumours of the trachea.1 Most resources and attention have for years

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you think

been directed at more common cancers which kill the majority of people. However, there are many more rare types and subtypes of tumours, clinically distinct entities, which, if taken together, account for a relatively high proportion of all cancers diagnosed in Europe every year. The EU project, Surveillance of Rare Cancers in Europe (RARECARE), proposed a definition to identify rare cancers by providing a list and estimating their burden in Europe.2

WHAT IS A RARE CANCER? Rare cancers are cancers that present specific problems in clinical decision-making, healthcare organisation and clinical research because of their low frequency and the resulting limited expertise available. Specifically, rare cancers are those with an incidence (number of new diagnoses) of less than 6/100,000 per year, corresponding to less than 30,000 new cases per year in Europe. Rare cancers are often defined according to the prevalence criterion of less than 50/100,000 per year,3 similar to rare diseases in general. However, prevalence (which reflects the total number of cases at any given time in a population) has shortcomings when used to measure cancer rarity. The prevalence of a disease usually depends on incidence and survival, but in cases of cancers with low incidence but good survival such as testicular cancers and thyroid carcinoma, using the prevalence criterion pushes them into the common category, because of their good survival rates. Similarly, some common cancers with poor survival, such as adenocarcinoma of the stomach and squamous cell and adenocarcinoma carcinoma of the lung, would be considered rare because their poor survival pushes prevalence down. This suggests that incidence is a better indicator for defining rare cancers, and is also in harmony with the sub-acute clinical course of most rare cancers. Most rare non-

How many doctors have ever diagnosed/ treated one of these tumours and how many oncology nurses have ever seen patients with such tumours? 17

neoplastic diseases, in contrast, have a chronic course, so prevalence is a better measure. According to the RARECARE definition, 186 tumours were identified as rare (the full list is available on the RARECARE website). Examples of rare cancers are cancers of the head and neck, some cancers of the digestive tract (tumours of the small intestine, anal canal and gallbladder), some cancers of the respiratory tract (tumours of the trachea, thymus and mesothelioma), sarcomas, tumours of the central nervous system, many haematological malignancies and all embryonal neoplasms. Rare cancers can also arise in common sites, as for instance metaplastic carcinoma of the breast, transitional cell carcinoma of the prostate, bronchiolo-alveolar carcinoma of the lung and many others. Despite the rarity of each rare cancer, they constitute all together 22 per cent of all cancers diagnosed in the European Union each year. In absolute terms, this is slightly more than half a million new rare cancer cases each year, with 4,300,000 people in Europe currently living with rare cancers. It is worth noting that 30 per cent of Europeans with a rare cancer have one of the particularly rare forms that affect less than 1/100,000. This is important, because low incidence is a major obstacle to conducting clinical trials to develop effective treatments. These figures give an idea of the high numbers of rare cancers patients and their relatively poor survival rate which, on average, is markedly lower than more common cancers (47 vs 65 per cent).1 RARECARE has produced a table showing estimates of incidence, survival and prevalence of major groups of rare cancers for EU27, together with expected numbers of new and prevalent cases per year in EU27. You can view this table at www. cancernurse.eu/magazine THE CHALLENGES OF RARE CANCERS Patients with these cancers and their families face a common set of difficulties arising directly from the rarity of these pathologies: ●● Misdiagnosis and delay in diagnosis: The period between the onset of the first symptoms and the appropriate diagnosis involves significant delays, as well as wrong diagnosis leading to inaccurate treatments.4-6 ●● Lack of scientific knowledge: The small number of patients undermines the possibility

Breakdown of rare cancers Rare haematological cancers constitute 22 per cent of all rare cancers, followed by rare cancers of the female genital tract (18 per cent), rare cancers of the head and neck and digestive tract (14 per cent), rare cancers of the respiratory tract (8 per cent), sarcomas and cancers of the central nervous system (5 per cent). The remaining – rare male genital cancers, endocrine, neuroendocrine (excluding the lung), nonskin melanoma – constitute less than 4 per cent each of all rare cancers.

to organise clinical trials and the available registries and tissue banks are few. This results in difficulties in developing therapeutic tools, and in defining a therapeutic strategy, hence a shortage of therapeutic products.4-6 ●● Lack of appropriate quality healthcare: The lack of appropriate medical expertise for the management of rare cancers, poor referral rates from general practitioners and pathologic misdiagnosis.4-6 Despite these difficulties, there are remarkable examples of success. Advances in treatment, as a result of clinical trials, have markedly improved

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prognoses for many childhood cancers – the majority of which are rare – over the last 30-40 years.7 Today, for most countries in Europe, survival in children ranges between 78 and 83 per cent.8 This success has been achieved through the development of treatment approaches that are multidisciplinary, risk-adapted, cooperative and multi-institutional (national and international). This can be applied to rare cancers in adults. In the world of adult oncology, it was the astonishing success of Glivec (imatinib) in two rare cancers – chronic myelogenous leukaemia (CML) and gastrointestinal stromal tumour (GIST) – that moved the field of molecular-targeted therapies into high gear and helped control these two fatal diseases. MEETING THE CHALLENGES There are many actions that can be taken to address the challenges associated with rare cancers. These include: ●● Establishing centres of expertise for rare cancers and networks of these centres across the EU to achieve the necessary organisational structure, expertise and involvement of patients for carrying out clinical trials. ●● Developing alternative study designs and methodological approaches to clinical experimentation, and improving accuracy and standardisation of staging procedures and treatment for rare cancers.4 ●● Developing a multidisciplinary clinical approach including creating the post of a case manager able to support the patient throughout the different steps of their pathway of care (from diagnosis to rehabilitation and, most important, psychological support). Oncology nurses can act as case manager, supporting patients along their complex clinical pathway and facilitating the management and delivery of quality clinical care in a time-constrained environment. ●● Spreading knowledge and good practice guidelines on rare cancers. ●● Increasing awareness amongst general practitioners and pathologists about rare cancers, especially the symptoms and tumour characteristics that signal the need to refer the patient for specialist intervention or second opinion (with a view to ensure timely and appropriate diagnosis and care).4 ●● Disseminating information tailored to the needs

Rare cancers are cancers that present specific problems in clinical decision-making, healthcare organisation and clinical research because of their low frequency and the resulting limited expertise available of patients and of all concerned stakeholders. A large part of patient care can be centered on the work of nurses, who should be encouraged to network to share information and experiences, and apply their knowledge, skills and experience to care for the various and changing needs of patients. It is therefore important that nurses should start to share such experiences and begin to be involved in the wider networking on rare cancers. ●● Supporting patient associations in building the capacity of patient groups, making a change for patients and making sure they are recognised as stakeholders in and not subjects of healthcare, with the final aim of improving the survival and care of cancer patients. ●● Continuing to encourage initiatives to put rare cancers on the map. Taken together, the rare cancers community is calling for a fresh look at how EU member states organise research and care, and for a transparent dialogue between states, regulatory bodies, industry, patient representatives, national health authorities and rare-diseases-oriented research communities. In this context, RARECARE will continue to work – with the support of a grant from the Executive Agency for Health and Consumers which helped initiate in summer 2012 a rare cancers information network (RARECARENet) – to provide comprehensive information on rare cancers to the community at large.

The table and details of the references cited in this article can be accessed at www.cancernurse.eu/magazine

euroSARC

Researching rare cancers Challenges and solutions

Jean-Yves Blay

Rare cancer patients are faced with particular challenges including late or incorrect diagnosis which may lead to inappropriate treatment, difficulties to access information, trials with limited quality, and the scarcity of registries. This situation points to the need for increasing collaboration between the different stakeholders in the search for new solutions.

Race cancers represent approximately 20% of all cases of malignant neoplasms. They occur more frequently in young patients, and are associated with a less favourable prognosis than common tumours. Their clinical presentation may not differ much from more common cancers â&#x20AC;&#x201C; the clinical diagnosis of a breast sarcoma, for instance, largely falls within the domain of breast cancer. However, they can also be atypical, which can make it hard for physicians. Because they are rare, they are more frequently misrecognised, and to diagnose them may take more time and often requires collaboration between the primary pathologist and a centre with expertise in this specific pathology. In sarcomas, inaccurate diagnosis of the tumours has been observed in up to one third of the tumours in population-based series, leading potentially to inappropriate treatments. Once diagnosed, the treatment

of rare cancers in a community setting may suffer from lack of knowledge of the disease and lack of strategic clinical decision-making by expert disease-oriented multidisciplinary teams.1 Limiting Factors and Challenges The first challenges for patients with a rare tumour are therefore to be diagnosed accurately, and to receive the best treatment if they are treated at a centre without much experience. There is general agreement among experts from all different fields of rare tumours that patients with rare cancers benefit from being managed at experienced multidisciplinary centres, from the quality of diagnosis, to the initial management in localised disease, through to access to experimental agents in innovative clinical trials. However, the settings in which rare tumours are managed differ between Euro-

pean countries, depending on reference centres, their funding, and the conditions of access. Reaching these centres may be complex for patients, who cannot easily find information on the best place to go to or how to get there. The internet and patient advocacy group communication materials are often major sources of information for the patients, their families, and sometimes also the general practitioners. Finding out about clinical trials is often the second set of challenges for patients with rare tumours. The development of clinical trials and translational research in rare cancers also presents challenges, given the limited size of the patient population which makes it harder for clinical researchers to build largescale randomised studies often required for efficacy assessment. Innovative statistical methodologies are therefore often used to properly assess efficacy. Unfortunately,

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low-powered trials that are too small to deliver convincing evidence, and failures in delivering the diagnosis, are often limiting factors for the development of research of high quality in these tumours. There is therefore a need for the clinical and translational research programmes dedicated to rare tumours to develop their work in large networks, or in intergroup multinational settings, often at a global level, to enable comparison of experiences and gather large series of patients, and biological material. This is however challenged by the differences in clinical trials legislation between countries and continents, which often prevent large-scale studies sponsored by an academic institution, as well as those conducted by pharmaceutical companies. Pharmaceutical companies, historically, have not been very engaged in the development of novel medications in rare cancers. This is however rapidly evolving, with the changing paradigms of personalised therapies focusing on specific molecular alterations which make rare tumours more attractive for drug development. However, regulations governing the development of new drugs – which affect mainly more common tumours – often make it hard to register new trials, when the magnitude and nature of benefit is questionable as it is applied to the entire patient population. This situation points to the need for increasing collaboration between the stakeholders working in rare cancers, which although individually rare affect one in five cancer patients when lumped together. The 2012 revision of the European Directive on cross-border health care, which formalised discussion between researchers, the European Medical Agency, reimbursement bodies and pharma, offers fertile ground to help ensure this difficult situation evolves favourably. Clinical research in rare cancers is also facilitated by the often well-organised networks of researchers dedicated to these tumours across countries and worldwide. Often, tumour banks, molecular characterisation, clinical research networks have been carried out earlier than in more common tumours, as can be seen, for instance,

Pharmaceutical companies, historically, have not been very engaged in the development of novel medications in rare cancers.

in paediatric oncology and haematology. Beyond paediatrics, the group of diseases of sarcomas – malignant tumours of the soft tissue – also exemplify the challenges, and possible solutions, for rare cancers.

MOLECULAR ALTERATIONS IN SARCOMA Sarcomas account for approximately 1-2 per cent of all cancers and constitute a heterogeneous group of rare tumours arising from the resident cells of connective tissue. The overall yearly incidence of sarcoma from all sites probably ranges from five to seven new cases /100,000 per year. Recent years have seen significant progress in understanding molecular alterations associated with sarcoma subtypes, which has allowed the development of drugs targeting crucial proteins involved in the neoplastic transformation of sarcoma cells.2,3 A wide variety of DNA alterations have been observed in sarcoma. These tumours can now be classified into distinct molecular and pathological entities – six molecular subgroups of connective tissue tumours may be distinguished: 1. sarcomas with specific translocations generating fusion genes whose protein products modulate transcription or may act as growth factors, e.g. EWS/Fli1 in Ewing sarcomas; 2. sarcomas with mutated activated kinases (KIT in GIST); 3. sarcomas with deletion of tumour suppressor genes such as NF1 sarcomas; 4. sarcomas with simple genetic alterations (MDM2/CDK4 amplification in well differentiated liposarcomas); 5. sarcomas with gross genetic alterations, e.g. leiomyosarcomas;

6. tumours with alterations of the intercellular adhesion pathways (aggressive fibromatosis with APC deletion or b-catenin mutations). The developments of new treatment approaches in these tumours have been following the same refinements, targeting more accurately specific molecular and histological subtypes. Targeting of KIT with specific tyrosine kinase inhibitors (TKI- imatinib, then sunitinib, and more recently nilotinib) has led to major improvement in the survival of these patients affected with an otherwise chemo- and radio-resistant disease. Trials with biologic agents targeting IGF1R, the mammalian target of the rapamycin (mTOR) pathway, erbB receptors (EGFR, HER2), angiogenic factors and heat shock proteins have been performed and/or are currently underway in other histologic subtypes, the novel therapeutic agents in clinical trials are therefore stratified for molecular subtypes in these diseases. This evolution is of interest at a time when more common tumours are being fragmented into more homogenous molecular subtypes, with distinct molecular alterations, e.g. mutation of BRAF. Some of these mutations may be shared by a variety of different malignant tumours. Whether this characteristic will guide the treatment to be selected in the future is not known. Still we are currently observing for all common tumours a fragmentation which is going to lead to problems similar to those discussed above. The challenges of rare tumours are therefore the challenges of the oncology of the future.

Details of the references cited in this article can be accessed at www.cancernurse.eu/magazine

Sharing clinical decision-making in the face of uncertainty The low incidence of rare cancers requires special methods and processes to address higher than usual uncertainty in clinical decision-making. This requires novel solutions with a special emphasis on building collaborative networks and working on a multidisciplinary basis.

BSIP SA / Alamy

are cancers are by definition problematic, in as much as the low incidence of a disease poses problems. They suffer from a lack of medical knowledge on two fronts: firstly clinical research is more difficult, so that evidence is much more difficult to build in comparison to common cancers, and secondly physicians are less exposed to these cancers in their everyday professional life, so that they are less “expert”. In the end, clinical “uncertainty” is higher. A patient with a rare cancer faces more uncertainty than average because clinical decision-making in rare cancers (and rare diseases in general) takes place under conditions of higher uncertainty than usual. It is important to realise that both weaknesses need to be addressed and that the solutions are different.

Paolo G. Casali

NEED TO ADDRESS UNCERTAINTY Improving clinical research into rare cancers can be done in two ways. Greater efforts can be made to enrol more patients with rare cancers into clinical trials. This is usually demanding because one needs to act internationally, perhaps globally, to accrue patients into trials. Given the limited expertise in the community, these efforts must be carried out with caution to avoid affecting the quality of care, and some treatments need to be undertaken almost exclusively within the reference centres. The other way would be to exploit new methodologies, such as new study designs, alternative statistical tools, etc.,

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that would allow enrolment of a smaller numbers of patients than usual. This may prove difficult, as the approach to medical statistics has tended be rather conservative. In any case, if we do not provide the clinician with more data from clinical trials, their clinical decision-making will take place under conditions of high uncertainty. The only solution then is to share this uncertainty with the patient, since each patient will have their own attitude toward uncertainty, so that two patients with the same disease may decide differently. It is important that patients realise that this is the only way to address uncertainty, as long as it cannot be reduced further. Of course, this may carry a degree of anxiety, and it will always be difficult for a patient to embark upon such a shared decision-making process under conditions of high uncertainty, while coping with a serious disease like cancer. SHARING CLINICAL DECISIONS Probabilities should be taken into account, whatever the uncertainty they carry, so that they will look like “distribution probabilities” with a wide variance. At the same time, patient “utilities” should also be considered, incorporating their attitudes toward risk and also uncertainty. This is not easy to do at the patient’s bedside. It is challenging for oncologists, general practitioners and nurses and, in fact, a multidisciplinary team must be involved in such difficult clinical decision-making. From a clinical point of view, solid cancers are always dealt with on a multidisciplinary basis. Therefore, a patient with a rare cancer needs to find a multidisciplinary team made up of people who are all experts in the disease and used to working on a multidisciplinary basis. The clinical decision must be genuinely shared with them, though it is already the result of a collaboration among several super-specialists. The adverse impact of the lack of expertise in the community can be limited only by proper patient referral. In fact, medical education is much less effective with rare diseases, since acquired knowledge is not reinforced in everyday practice. As medical education works much less effectively, the tools to spread medical knowledge need to be different from those used in more common diseases. Centres of excellence, or reference centres as they are also called, are the solution. They are, however, not widespread, not easy to access and likely to be overwhelmed with waiting lists and problems with delivering routine care, resulting in health migration. Collaborative healthcare networks may be the right answer. These are much more feasible

A patient with a rare cancer needs to find a multidisciplinary team made up of people who are all experts in the disease and used to working on a multidisciplinary basis today than a few years ago, since information technology has finally made its way into medicine. One of the problems, however, is that sharing a patient amongst many centres means that more physicians will have to be involved, which costs medical time and, in the end, money. While health migration is paid for by patients and their families, medical time is paid for by health systems; and these face difficult times today. TACKLING THE METHODOLOGY In order to address all the problems rare cancers pose to the clinical decision-making process, a wide range of methodological and organisational problems in clinical research must be tackled, including building collaborative networks and working on a multidisciplinary basis. Clinical decisions will often be made under conditions of higher uncertainty than with common cancers, and this requires a clinical method and process which is challenging and involves several players in itself, in addition to challenging the patient at a difficult time in their life. From the methodological point of view, an added value of rare cancers is that they present challenges that require new solutions. They also present new opportunities because the solutions may well apply to common cancers as well. Today cancer is looking more and more like a variegated set of diseases. The introduction of targeted therapies is splitting up common cancers into a formidable number of subgroups, so that the incidence of each of them may be rather low. In the end, common cancers are becoming rare themselves. “Personalised” oncology is the new term used to describe this state of affairs. Personalising cancer treatment should be a duty for all oncologists, by looking not just at the biomolecular tumour profile, but also at patients’ values, quality of life, etc. It is now urgent to address the universal need to personalise cancer treatment as far as possible. Rare cancers may well serve as a good laboratory within which there is no option other than trying new solutions for “personalised medicine”.

Kerstin Westermark

Regulating orphan drugs in The development of new pharmaceutical products for rare diseases has been boosted by successive Orphan Regulations promulgated by the European Commission. Key to their success is effective collaboration between member states, pharma, sponsors, patients and networks. The term “Orphan medicinal products” refers to a group of medicines for the treatment of conditions so rare that the cost of developing and bringing them to the market would not be recovered by the expected sales. Hence the need for two crucial EU laws – the Orphan Regulations (EC) 141/2000 and Regulation (EC) 847/2000 – which state that: “Persons suffering from rare conditions should

be entitled to the same quality of treatment as other patients”; while recognising that “the pharmaceutical industry would be unwilling to develop the medicinal product under normal market conditions… [as] some conditions occur so infrequently that the cost of developing and bringing to the market a medicinal product (…) would not be recovered by the expected sales.”

ORPHAN DESIGNATION Orphan Regulation 141/2000 offers a number of incentives for orphan medicinal products (OMPs), such as waived/ reduced fees for scientific advice (‘protocol assistance’) and marketing authorisation applications, as well as 10 years of ‘market exclusivity’ from the date the new therapy receives market authorisation for a specific therapeutic orphan condi-

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The role of patients is to bring ‘real-life’ experience, increase transparency and build confidence in the regulators’ work

nation are given by the Committee for Orphan Medicinal Products (COMP) at the European Medicines Agency (EMA), with the final decision on approval being made by the European Commission (EC).1

SMITH COLLECTION/GETTY

Europe tion. The criteria for orphan designation requires that the pharmaceutical product is intended to diagnose, prevent or treat a medical condition affecting not more than 50 in 100,000 persons in the community (‘prevalence’ criterion) or that, without incentives, the product would be unlikely to generate sufficient return to justify the necessary investment (‘non-return on investment criterion’). Furthermore, the condition should be proved to be life-threatening or chronically debilitating (‘seriousness criterion’) and that no satisfactory treatments are already available, or if they are, the sponsor should establish that the product will be of significant benefit for those suffering from the condition (‘significant benefit criterion’). Opinions on Orphan Desig-

A SINGLE APPLICATION Orphan regulations have undoubtedly been a resounding success. Before their promulgation, there were only a handful of OMPs on the market. But since, industry has seen a rapid expansion of micro-, small- and medium-sized enterprises in orphan drug development whereby small pharma had developed into big pharma and big pharma increased their interest in orphan drug niches. Healthcare professionals/academia were among the sponsors of orphan designation applications. Approval regulations also became easier thanks to the decision of the EC to centralise applications for marketing authorisation to the EMA, replacing a system where each drug had to be approved through the national procedure of each member state separately. Subsequently, more than 900 positive opinions have been given by the COMP, resulting in more than 60 marketing authorisations for around 50 different rare conditions. Rare cancers has been the area attracting the highest interest from sponsors of OMPs, corresponding to around 40 per cent of orphan designations and also around 40 per cent of marketing authorisations. Out of the more than 60 marketing authorisations to date, around one third are for treating rare cancers. Haematological malignancies have been the most successful – four OMPs for acute lymphoblastic leukaemia, three for acute

myeloid leukaemia and three for chronic myeloid leukaemia have reached the market since the orphan regulations came into force. Approval of orphan medicinal products, as for all cancer drugs, must go through the EC’s ‘centralised marketing authorisation procedure’ by which a single application is sent to the EMA whose work depends on the network of 27 member states, as well as Norway and Iceland. The assessment of Marketing Authorisation Applications (MAAs) is carried out by the Committee for Medicinal Products for Human Use (CHMP), where two member states act as Rapporteur and Co-rapporteur. Following a positive opinion by the CHMP on the benefit/risk balance, the EC gives a decision on approval. The orphan designation is reviewed by the COMP during the MAA process (see box). If the criteria are not fulfilled, the product may be given a ‘normal marketing authorisation’ but not a market exclusivity. A 2011 evaluation of the 64 marketing authorisations found that more than half (51%) were for diseases affecting fewer than 10 in 100,000 people, illustrating the difficulties encountered when developing products for rare diseases. Almost 40 per cent of the marketing authorisations are given ‘under exceptional circumstances’ because the rarity of the condition makes it hard to obtain comprehensive information on efficacy and side effects and, at the same time, the seriousness of the condition means there is an ethical imperative not to withhold treatment from patients. This results in extensive post-marketing obligations for the sponsor. In a small number of cases, additional information

is requested and ‘conditional authorisation’ is given. In this case, new studies have to be done in order to maintain marketing authorisation.2 ACCESS TO TREATMENT At EMA level, the work done includes the orphan drug designation, protocol assistance, paediatric investigation plan, marketing authorisation (MA) including review of orphan designation criteria at the time of MA application, post-MA obligations, additional studies and follow-up registries. What is not done in common includes the assessment of clinical added value (CAV) – ’real life’, health economic assessments and pricing and reimbursement is strictly undertaken at national level. This frequently results in a delay in accessing treatment for patients in many EU countries, although OMP is authorised in all member states. If new orphan drugs are not marketed in (small) countries due to lack of reimbursement or of financial resources in hospitals, patients will have no access to treatment, despite all the incentives provided by orphan regulations. Due to the limited data available at the time of marketing authorisation to inform on health technology assessments and pricing/reimbursement decisions, the issue of how to facilitate patient access to OMPs requires further studies. Access could depend on EU-follow-up systems/ registries collecting data on drug effectiveness, i.e. the real-life value of OMPs based on a significant number of patients and a realistic time frame. Financing could be provided at EU level to support infrastructures/registries and at national level to support early introduction and rational use of orphan drugs, e.g. conditional pricing. This would allow for rapid access to treatment while collecting large amounts of data, while at the same time allowing for rapid decisions on the value for money without withholding treatments for patients. Moreover, national rules for named-patient-prescription of OMPs as well as compassionate use programmes can be used to help patients who cannot be treated satisfactorily by an available medicinal product.

Orphan designation To qualify for orphan designation, a medicine must meet the following criteria: ●● it must be intended for the treatment, prevention or diagnosis of a disease that is life threatening or chronically debilitating; ●● the prevalence of the condition in the EU must not be more than 50 in 100,000 or it must be unlikely that marketing of the medicine would generate sufficient returns to justify the investment needed for its development; ●● no satisfactory method of diagnosis, prevention or treatment of the condition concerned can be authorised, or, if such a method exists, the medicine must be of significant benefit to those affected by the condition. Applications for orphan designation are examined by the EMA’s Committee for Orphan Medicinal Products (COMP), using the network of experts that the Committee has built up. The evaluation process takes a maximum of 90 days from validation. (From www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/general/ general_content_000029.jsp&mid=WC0b01ac05800240ce)

COLLABORATION OF ALL STAKEHOLDERS Key to success in the development of OMPs in the EU has been collaboration between all member states. This example opens opportunities for EU collaboration to be extended to health technology assessment (HTA) with the same objective – to avoid duplication of efforts for industry/HTA bodies and national authorities. One such example is the ‘CAVOD’ project, to create a mechanism for the exchange of knowledge between member states and European authorities on the scientific assessment of the Clinical Added Value for Orphan Drugs.3 Other initiatives are the development of disease-based community registries and projects such as EPIRARE and PARENT which are EU-wide networks based on national centres for rare diseases. The importance of the patient contribution to drug development has been increasingly recognised – from the start of the COMP in 2000, when three patient

representatives were the first to become full members of an EC Committee, until today, when patient representatives are important partners of virtually every new committee created at the EMA. Their roles are to bring ‘real-life’ experience, to increase transparency and build confidence in the regulators’ work, and also to bring in the patient perspective and initiate the change of rules and regulations when necessary and in the interest of patients. The recipe for success is thus: EU collaboration, collaboration and more collaboration!

The views expressed in this article are the personal views of the author and may not be understood or quoted as being made on behalf or reflecting the position of the European Medicines Agency (EMA) or one of its committees or working parties. Details of the references cited in this article can be accessed at www.cancernurse.eu/magazine

EONS 30th Anniversary Event Thursday, 10 April 2014 The Royal Marsden, London, UK This special 30th Anniversary Event will be held at The Royal Marsden in London, where EONS began in 1984. The event will celebrate EONSâ&#x20AC;&#x2122; achievements and will bring together Presidents (past and present) Board Members (old and new) and other stakeholders to reflect on the challenges and development of cancer nursing over the past 30 years and into the future. This is an invitation only event with a limited number of places.

For further information please contact: anniversary.event@cancernurse.eu

Rare Cancers:

More joint action than you think!

Rare Cancers Europe is a multi-stakeholder partnership initiative dedicated to addressing issues of particular relevance in rare cancers, including methodological and regulatory barriers, the need for centres of expertise and European reference networks, barriers to patientsâ&#x20AC;&#x2122; access to care, education of healthcare professionals and access to information on rare cancers. For more information, please visit www.rarecancerseurope.org.

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Thinking outside the box is key As even common cancers fragment into multiple smaller disease entities, cancer communities must prepare to say goodbye to traditional research paradigms and get smarter at gathering and using every bit of evidence.

Robert Schaefer

are cancers are sometimes referred to as a precursor of things to come in oncology. In an era of molecular diagnostics and targeted therapies, where more and more common cancers are subdividing into increasingly smaller molecular subtypes, it is no longer taboo to say that soon all cancers will be rare. This will affect not only the way cancers are traditionally classified and registered, but will also have an impact on clinical and translational research, drug development, diagnostics and, most importantly, the treatment and care of cancer patients. With common cancers splitting up into hundreds of molecularly distinct cancer types, and with diagnostic tools and techniques getting ever more sophisticated, one might think that the smaller the cancer entities, the easier it will be in future to detect them in a timely fashion and treat them effectively. Yet even though some of the most striking effects of novel cancer treatments are seen in rare cancers, there is no guarantee that conducting clinical studies based on cancer genetics and molecular pathways, and developing targeted treatment approaches, will help decrease overall cancer mortality. It also remains to be seen what impact this development will have on drug approval and reimbursement rates and on the still prevailing inequalities in patient access to (novel) cancer treatments across Europe.

NEW THERAPIES Targeted therapies may be successfully developed for a variety of smaller cancer subtypes, but there may still be many other rare cancers where new treatment options are either unavailable or ineffective, and doctors and patients still have to decide which conventional “hit-or-miss” treatment approach to follow. In addition, it will become increasingly challenging to study the effect of experimental therapies in smaller cancers, as patient populations with a specific genetic profile will necessarily also be smaller, hence it will become even more difficult to recruit sufficient numbers of patients for conducting (international) practice-changing studies. It is therefore crucial to allow for greater flexibility in clinical research, for example, by using Bayesian probabilities for summarising evidence, or by investigating several rare cancers in a single study while borrowing information between different histologies to obtain sufficient amounts of evidence. A recent study following this approach enrols patients with a specific genetic fingerprint across various solid and haematological cancers, thus increasing the number of cancers investigated as well as the overall patient population. There are concerns that this approach might be “abused” for obtaining drug approvals in more common cancer

indications, but the increasing role of biomarkers is being acknowledged in the European Medicines Agency’s revised guideline on the evaluation of human anticancer medicines (see box, p31). Making sure that research, drug development and healthcare infrastructures keep pace with recent developments continues to be a major challenge, and it is becoming increasingly clear that the key to success in rare cancers no longer lies in generating and enhancing specialist knowledge and expertise alone. It is also necessary that all parties involved are more prepared than in the past to accept probabilities gained from previous research and from clinical practice. This means that strictly separating rare cancer research from care is no longer helpful and there is also a need to say goodbye to 19th century belief systems where every hypothesis can be “objectively” tested, quantified and repeated. Non-frequentist multi-histology approaches even imply that traditional distinctions between rare solid cancers and haematological malignancies may become more and more obsolete. The smaller a cancer patient population, the more important even small pieces of quality information become in terms of gathering available evidence and informing decisions in cancer research, diagnosis, treatment and care. For example, information concerning the off-label use of drugs can be very helpful in the rare cancers arena, even if the treatment in question did not work. All parties involved should therefore significantly step up cross-border networking, collaboration and communication within, between and beyond their respective stakeholder communities and establish a spirit of transparent and proactive sharing to make pertinent information available to all relevant stakeholders as early as possible.

SETTING UP ONLINE DATABASES To facilitate this, ideally without adding to the existing fragmentation of cancer registries, wellstructured online databases could be set up for collecting and sharing valuable information, data and evidence with relevant stakeholders, also including centres of expertise and reference networks. Orphanet, a reference portal for rare diseases and orphan drugs, EPIRARE, the European Platform for Rare Disease Registries, the European Network of Cancer Registries (ENCR), RARECARENet, a planned information network on rare cancers, and eurocancercoms, an online

cancer communication platform, and similar projects may provide opportunities for synergies. The European Organisation for Research and Treatment of Cancer (EORTC) makes data from its clinical studies available to other academic researchers. The Organisation of European Cancer Institutes (OECI) has established a platform to

There is a need to say goodbye to 19th century belief systems where every hypothesis can be “objectively” tested, quantified and repeated

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journals beneficial for their research and say they would improve the way their community works, yet only around 10% of articles are published in open access journals. In the clinical setting, interprofessional collaboration and communication within the multidisciplinary healthcare team should always also integrate pathologists, nurses and patients as equal members. Continuous collaboration with general practitioners could help obtain valuable information on how specific treatments work in other patients outside the controlled hospital environment. Frequent delays in rare cancer detection and the high rate of incorrect diagnoses could be addressed by establishing platforms for submitting pathology reports for second opinion and by setting up educational programmes jointly developed and implemented by professional societies and professional education and training organisations active in haematology, oncology, pathology and general practice. Much of this sounds self-evident but examples are still â&#x20AC;&#x201C; rare.

The views expressed in this article are the personal views of the author and may not be understood or quoted as being made on behalf or reflecting the position of the European Society for Medical Oncology (ESMO) or Rare Cancers Europe or any of the parties involved in this initiative.

European Medicines Agency: Revised guidelines on the evaluation of anticancer medicinal products

identify cancer biobanks and exchange samples (OECI-TuBaFrost), but efficient European infrastructures are yet to be developed. Professional haematology and oncology societies and education and training organisations could set up free moderated online discussion platforms where professionals could post and discuss difficult rare cancer-related questions and exchange best practice. An increased use of open access journals could help overcome publication restrictions caused by impact factor and other biases, and accelerate the dissemination of scientific evidence. A recent global study concluded that 90% of scientists find open access

The European Medicines Agency is an agency of the European Union, located in London, which is responsible for the scientific evaluation of medicines developed by pharmaceutical companies for use in the European Union. It carried recently a revision of its guideline on the evaluation of anticancer medicines which, as well as defining the proper doses and schedules for a medicine, highlighted the importance of identifying the target population during the development. The revision included, the use of biomarkers, combination-therapy studies and the choice of endpoints in confirmatory trials. Two appendices in the guideline addressed methodological considerations for using progression-free survival in confirmatory trials, and gave specific guidance for chronic myeloid leukaemia (CML), myelodysplastic syndromes, haematopoietic stem cell transplantation, non-small-cell lung cancer (NSCLC) and prostate cancer. The revised guideline came into effect on 1 July 2013. It can be accessed at www.ema.europa.eu/docs/en_GB/document_library/ Scientific_guideline/2013/01/WC500137128.pdf

The European Oncology Nursing Society presents:

www.cancernurse.eu

EONS 9 Autumn Convention

Istanbul, Turkey 18-19 September 2014

SAVE THE DATE!

Two days of specialist cancer nursing educational workshops, scientific news, and networking opportunities at the Military Museum and Cultural Center in the lively city of Istanbul.