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Article type: Special Article

Short-Title: ESMO Position Paper on Supportive and Palliative Care

Author list: K. Jordan1, M. Aapro2, S. Kaasa3, C. I. Ripamonti4, F. Scotté5, F. Strasser6, A. Young7, E. Bruera8, J. Herrstedt9, D. Keefe10, B. Laird11, D. Walsh12, J.Y. Douillard13

and A. Cervantes14

Affiliation list : 1 Department of Medicine V, Hematology, Oncology and Rheumatology, University of Heidelberg, Germany. 2 Cancer Center, Clinique de Genolier, Genolier, Switzerland. 3 Department of Oncology, Oslo University Hospital, University of Oslo, and European Palliative Care Research

Centre (PRC) NTNU, St Olavs hospital, Oslo, Norway. 4 Supportive Care in Cancer Unit, Department of Onco-Haematology, Fondazione IRCCS Istituto Nazionale Tumori,

Milan, Italy. 5 Supportive care in cancer unit, Department of Oncology, Foch Hospital, Suresnes, France. 6 Oncological Palliative Medicine, Clinic Medical Oncology and Hematology, Department of Internal Medicine,

Cantonal Hospital St Gallen, St Gallen, Switzerland. 7 Warwick Clinical Trials Unit, University of Warwick Coventry; United Kingdom. 8 Department of Palliative, Rehabilitation and Integrative Medicine, The University of Texas, MD Anderson Cancer

Center, Houston, USA. 9 Department of Oncology Zealand University Hospital Roskilde, Denmark, University of Copenhagen,

Copenhagen, Denmark.10 Department of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, Australia. 11 University of Edinburgh, Edinburgh UK & St Columba's Hospice, Edinburgh, UK.12 Academic Department of Palliative Medicine, Our Lady's Hospice and Care Services, Dublin, Ireland. 13 Chief Medical Officer, ESMO, Lugano, Switzerland. 14 CIBERONC. Department of Medical Oncology, Institute of Health Research INCLIVA, University of Valencia,

Valencia, Spain.

Full address for correspondence:

Prof. Dr. med. Karin JordanDepartment of Medicine V Hematology, Oncology and RheumatologyUniversitätsklinikum HeidelbergIm Neuenheimer Feld 41069120 HeidelbergTel. +49 (6221) 56 6435E-Mail: karin.jordan@med.uni-heidelberg.de

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European Society for Medical Oncology (ESMO) Position Paper on Supportive and Palliative Care_________________________________________________________

Abstract: Oncology has come a long way in addressing patients’ quality of life, together with developing surgical, radio-oncological and medical anti-cancer therapies. However, the multiple and varying needs of patients are still not being met adequately as part of routine cancer care. Supportive and palliative care interventions should be integrated, dynamic, personalised and based on best evidence. They should start at the time of diagnosis and continue through to end-of-life or survivorship.

ESMO is committed to excellence in all aspects of oncological care during the continuum of the cancer experience. Following the 2003 ESMO stand on supportive and palliative care1, this position paper highlights the evolving and growing gap between the needs of cancer patients and the actual provision of care. The concept of patient centred cancer care is presented along with key requisites and areas for further work.

Key words: position paper, ESMO, supportive care, palliative care, patient centred care, multi disciplinarity

Topic: supportive care and palliative care

Key message: ESMO aims to call attention the evolving and growing gap between the needs of cancer patients and the actual provision of patient centred care, including supportive, palliative, end-of-life and survivorship care.

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IntroductionBased on GLOBOCAN estimates, about 14.1 million new cancer cases and 8.2 million cancer-related deaths occurred in 2012 worldwide 2. Due to the accelerated pace of progress in diagnostics and treatments, more patients are now cured or live longer with metastatic disease.

Nevertheless, a cancer diagnosis, the disease itself and the sequelae of anticancer treatment are major stress factors for patients. Over the last decade clinicians have accepted that, while survival and disease-free survival are both fundamental factors, overall quality of life (QoL) is also crucial for patients. The latter evidenced by the increasing use of QoL as high-level endpoints in clinical trials of anti-cancer therapies3, 4, 5.

Depending on diagnosis, cancer patients will receive different types and intensities of tumour-directed treatment (i.e. antineoplastic therapy, radiotherapy and/or surgery). Along with anti-tumour treatment, most patients need help to prevent and alleviate side effects and toxicities, and to cope with the disease itself. Furthermore - at any stage of the cancer pathway - physical, psychological, social, existential and spiritual support and rehabilitation, is often needed. For optimal management, patients must be fully involved in the decision-making process.

Building on previous ESMO policy statements and guidelines, and considering the unfulfilled needs of cancer patients, this position paper advocates for patient centred care (including supportive and palliative care) to be integrated by a multi-disciplinary team (MDT) to anticancer treatment, from the time of diagnosis and throughout the continuum of disease, including end-of-life and survivorship care.

ESMO is committed to increasing awareness and education to bring patient centred care closer to all professionals, to improving collaboration between healthcare providers for the good of patients and to promoting research, so that patient centred interventions are not only integrated, but also based on the best evidence.

This paper was prepared by parts of the ESMO Faculty Group on Supportive Care and Palliative Care. A meeting coordinated by the ESMO Educational Committee was held in May 2017 to discuss the content and structure of the paper. The draft went through several rounds of review by the Group and was approved by both the group and the Educational Committee Chair.

Supportive and palliative Care: all about the patientClinicians have always intended to provide the best care for their patients. However, health systems do not always enable this. Consciously putting patients’ holistic needs at the centre of everything is the cornerstone of supportive and palliative care. This position paper goes beyond the debate about the standard definitions of supportive, palliative and end-of-life care. Much work has already been done in this area 6, 7, 8.

Two widely accepted definitions are provided below as examples.

The Multinational Association of Supportive Care in Cancer (MASCC) has proposed the following definition of supportive care: “Supportive care in cancer is the prevention and management of the adverse effects of cancer and its treatment. This includes management of physical and psychological symptoms and side effects across the continuum of the cancer experience from diagnosis through anticancer treatment to post-treatment care. Enhancing rehabilitation, secondary cancer prevention, survivorship, and end-of-life care are integral to supportive care” 9.

The World Health Organisation (WHO) has proposed the following definition for palliative care: “Palliative care is an approach that improves the quality of life of patients (adults and children) and their families who are facing problems associated with life-threatening illness. It prevents and relieves suffering through the early identification, correct assessment and treatment of pain and other problems, whether physical, psychosocial or spiritual. Addressing suffering involves taking care of issues beyond physical symptoms. Palliative care uses a team approach to support patients and their

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caregivers. This includes addressing practical needs and providing bereavement counselling. It offers a support system to help patients live as actively as possible until death” 7.

While definitions are important and studies have shown that the word “palliative” may have negative connotations for patients and could even delay their referral or readiness to accept interventions (when there is a lack of education or awareness of what supportive and palliative care entails) 10 ,

efforts must be focused on alleviating patients’ physical symptoms and psychological concerns, rather than on debating definitions.

The ESMO Supportive and Palliative Care Faculty proposes the use of the term “patient centred care” 11,12 to encompass both supportive and palliative care. To offer optimal patient centred care, institutions should be organised (according to their structure and goals) in a way to make this possible, with the necessary level of professional competence, skills and a collaborative organisation that facilitates care pathways, individualised according to the needs of each patient.

The patient centred care approachIndividual cancer patients will express different physical, psychological, social, existential and spiritual needs at different stages of the disease, that will often evolve over time. Therefore, patient centred care cannot be standardised, even though it is provided through a standard framework. To ensure that patients can voice their needs, oncologists should incorporate detailed and routine physical and psychological assessments allowing for supportive and palliative interventions to be personalised and integrated in the continuum of care. Patient reported outcomes (PROs) should be highly encouraged as requesting them has shown to be associated with better quality of life, fewer hospitalisations and even increased survival compared with usual care 13 .

Patient centred interventions should be routinely discussed and evaluated by the MDT, together with tumour directed treatment, respecting patient preferences and cultural specificities.

Key patient centred care interventionsThe MDT caring for patients should be able to address their multiple and varying needs. The following Table 1 shows some examples of key patient centred care interventions regarding assessment, monitoring and management strategies.

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ASSESSMENT MONITORING and INTERVENTIONRegular changes in patients’ health status preferably assessed with PROMs* or other validated assessment tools

MANAGEMENT of

Cancer-related symptoms and other needs

MANAGEMENT of

Anticancer treatment-related, toxicities and complications including prevention

Cancer and anticancer-treatment related symptoms, toxicities, complications

Psychological disorders, distress

Sleeping problems Spiritual and existential

issues Comorbidities Nutritional status Sexuality concerns Prognosis and coping with

cancer disease Family and/or caregiver

issues Socioeconomic issues Other unmet needs

Adverse events of anticancer treatment, specifically under immunotherapy

Compliance/adherence to oncologic treatments (e.g. oral antineoplastic agents)

Frequency of unplanned visits and/or unplanned hospitalisation

Special survivors’ needs Coping mechanisms Understanding of illness, treatment

and care options Patient and caregiver information

(including help from cultural mediators when needed)

Treatment decision making Advance care planning Preparation for end-of-life and

dying Family distress and care-giving

roles Professional support networks Loss of autonomy Distress Existential, spiritual and religious

needs Other monitoring and intervention

issues

Pain Fatigue Nausea and vomiting Constipation, diarrhoea Anorexia, cachexia, early satiety Dyspnoea / Breathlessness Hydro electrolytic disorders Prevention of skeletal related

events in patients with bone metastases

Anxiety Depression Sleeping disorders Evacuative paracentesis Endurance, resistance and balance

training Support in understanding the

disease itself as well as the diagnosis, treatment options and prognosis

Supporting decisional processes of patient & family

Organising and coordinating community support networks

Coping with life limiting expectancies

Other management issues

Nausea and vomiting Anaemia Febrile neutropenia Fatigue Pain Infections Dermatotoxicity Neurotoxicity Immune related adverse

events Diarrhoea/ constipation Mucositis Renal impairment, Cardiotoxicity Problems with sexuality Endocrine disorders Arthralgia Prevention of CTIBL** Prevention of infertility Maintenance of central

access devices Hydro electrolytic

disorders Other symptom

management issues

* PROMs Patient Reported Outcome Measures; **CTIBL Cancer Treatment Induced Bone LossTable 1. Key patient centred care interventions (examples)

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Timely patient centred interventions Patient centred care should be offered during the continuum of illness, from the time of cancer diagnosis through to survivorship or end-of-life. Needs will evolve together with the disease and anticancer treatment, so ongoing and careful holistic evaluation of requirements should be part of every consultation (see section on key interventions above).

For some patients diagnosed at an early stage, the treatment period is relatively short and, after follow-up, they become long-term survivors or are considered cured. For these patients, rehabilitation, prevention and management of adverse side effects are most important. Some patients will have one or more comorbidities at the time of their cancer diagnosis that may require intervention before the start of treatment; others may need rehabilitation due to treatment-induced long-term adverse effects. When cancer patients have advanced disease at the time of diagnosis, cure is usually not possible (Figure 1, palliative phase and end-of-life phase) and palliative care should be considered from diagnosis onwards14.

Recent studies show variable effects of the integration of early supportive/palliative care interventions. A few systematic reviews concluded that early palliative care in patients with advanced cancer significantly15 or slightly16 17.improved patients’ quality of life and could decrease symptom intensity, although overall survival was not prolonged. The most recent studies were not included in these reviews. These results include negative studies18. The overall impression is that early integration of palliative care is beneficial to patients with advanced cancer at the time of diagnosis19.

Recently, dedicated outpatient supportive care teams focusing on prevention and management of anticancer treatment toxicities have been developed20, 21. Data from Italian22 and French23 dedicated supportive care units show a reduction of unplanned hospitalisations of cancer patients undergoing treatment24 and for those requiring blood transfusion25 , allowing for cost effective management of symptoms and anticancer treatment-related toxicity in an ambulatory setting26. However, current literature is still scarce on supportive care units, so more RCTs should be encouraged in this field.

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Survivorship, Pre and RehabilitationAlthough patient centred care is needed throughout the disease, some phases deserve specific attention and more research. For example, due to the improvement of anticancer therapy efficacy, millions of patients today survive and live with a history of cancer. For them, ESMO encourages oncologists, in partnership with MDTs, to develop programmes of:

- Prehabilitation (at the time of diagnosis or relapse) to reduce frailty and prepare patients to receive adequate treatment. Prehabilitation may also reduce post-treatment disorders 27, 28.

- Rehabilitation) to reduce acute and chronic disabilities due to antineoplastic treatments. The ob-jective is to help patients become and remain independent and productive members of society, or to cope better with remaining limitations 29. Rehabilitation, however, can also be applied in palliat-ive situations.

- Survivor care plans, to support patients in recovering “wellbeing” in their personal, professional and social lives, may reduce the risk of recurrence and help manage chronic disease, but further research is needed on how to apply them in clinical practice 30 ,31 ,32.

End of life careSpecial attention should be paid to patients and their caregivers when life prolonging treatment comes to an end. In order to help them cope with this transition, advanced care planning 33 as a tool should be used early in the course of palliative chemo and radiotherapy. Near the end-of-life 34, particularly during the last days, these plans need to be adapted to patients and family members’ individual needs, based on an open communication about the natural course of the disease and the dying process 35.

“Advanced directives” should be discussed when appropriate, at any time in the disease trajectory, allowing patients to spell out their wishes about end-of-life care ahead of time. Discussing the patient’s status and prognosis can be challenging for professionals, therefore communication skills are essential.

Oncologists should be prepared to respond to emotions and to discuss the possible outcomes of cancer, including death. Professionals should be able to understand what matters most to patients and their families, to explain options simply and clearly, to help patients anticipate and plan in a way that is respectful of their wishes. This includes respecting the patient’s right to refuse treatment.

The UK’s National Institute for Health and Care Excellence (NICE) offers useful guidelines for care, as well as for pharmacological and non-pharmacological interventions, in the last days of life 36, although the UK health care system including hospices may not be transferable to other countries.

Multi-disciplinary teamsThe list of professionals that compose a MDT caring for patients includes several specialties. In summary, there should be medical oncologists, palliative medicine specialists, nurses, tumour origin specialists, radiation oncologists, surgeons, pharmacists, allied healthcare professionals, clerics and volunteers involved. A more extensive list of professions that may be included in the MDT is provided in the online supplement (see Table 2). Of course, not all patients will need the involvement of all these professionals.

The composition of the MDT, as well as tasks and responsibilities, will vary according to patient needs, resources and national settings. Nevertheless, the team should encompass medical and non-medical professionals that can take care of a wide variety of physical, psychological, social and existential needs.

If, due to financial or organisational limitations, the cancer centre does not have the necessary staff in-house to cater to all patient needs, patients should be referred to other centres or to individual, trained, professionals (such as physiotherapists or psychologists) where they have access to necessary interventions. It is important that the medical oncologist in charge of treatment and care is

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also responsible for coordinating these interventions and regularly evaluates the efficacy of patient centred care 37.

Integrating healthcare resourcesESMO has a long-term commitment to advance the integration of supportive and palliative care in oncology and to excellence in all aspects of oncological care.

Integration is needed to coordinate care processes, including establishing what health care resources are needed: “the correct competence in the right place at the right time”. The concept of integration of palliative care into oncology has received substantial attention recently although there is still no consensus on a definition of “integration.” In a recent article, Hui and Bruera 38 summarized 38 aspects of integration based on a systematic review, which were classified under 5 categories (clinical structure, clinical process, education, research, and administration). Subsequently, an international Delphi panel highlighted 13 criteria as major indicators of integration which may be useful for benchmarking palliative care access across healthcare systems 39.

In order to improve the current situation, ESMO is committed to expanding cooperation with other professional medical associations and organisations worldwide (such as the European Association of Palliative Care [EAPC], the Multinational Association of Supportive Care in Cancer [MASCC] etc.) and to encourage and sustain supportive and palliative care development through its "ESMO Designated Centre of Integrated Oncology and Palliative Care" programme 40, 41 .

Adequate patient centred care should be provided as part of the global service of every hospital or clinic treating cancer patients. Integrating patient centred services is the best way to ensure that they will be widely available and acceptable to professionals and patients alike. The Eligibility Criteria Checklist of the ESMO Designated Centre of Integrated Oncology and Palliative Care programme can be seen on the ESMO website 42 .

Resources being limited, not all oncology centres will have an extended MDT (and not all patients will need support) but, as a minimum, regular routine patient assessment of physical and psycho-social needs should be offered, as well as provision of interventions, whether in-house or by referral to medical or non-medical professionals.

Need for specific training in patient centred careESMO is committed to specialised education supporting oncologists in a fast-changing professional environment. The society aims to help oncologists gain in-depth, disease-specific knowledge as well as learning how to collaborate effectively with other specialists in an integrated, multi-professional setting.

Medical oncologists should be trained in the supportive and palliative care of patients, including basic knowledge about physical, psychological, social and spiritual aspects of cancer, as set out in the ESMO/ASCO Recommendations for a Global Curriculum in Medical Oncology (see Table 3) 43. As such a structured rotation in supportive and palliative care for oncology trainees would be a helpful approach. Furthermore, as stated in 2003, ESMO considers oncologists “should be familiar with the roles of other professions in the care of patients with cancer and with community resources to support the care of these patients.” If specialist patient centred care is required, oncologists should be able to identify which appropriate professional the patient should be referred to.

National Societies should also promote continuing medical education (CME) in the basics of patient centred care, to ensure professionals learn about new developments in the field.

Requirements of the ESMO/ASCO Curriculum are addressed in the following sections:

Complications/Toxicities of anticancer treatment Supportive care measures Palliative care

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End-of-life care

They encompass the following objectives (Table 3):

Table 3: Requirements of the ESMO/ASCO Curriculum To be able to assess, diagnose and treat patients with complications/toxicities of anticancer

therapies To be able to understand, evaluate and provide supportive care to patients with cancer,

including management of symptoms from the cancer and side effects of therapy from the time of diagnosis until death or until rehabilitation and survivorship issues have been successfully managed

To know the indications for the different supportive treatments and their limitations and side effects

To be aware of the importance of a multidisciplinary approach To be able to screen for, assess, prevent and manage symptoms of patients with cancer

such as pain, fatigue, anorexia, anxiety, depression, breathlessness and nausea To communicate effectively with patients and families about illness understanding and

coping with it, prognosis, difficult decisions, end-of-life and its preparation To recognise the role of cancer rehabilitation, including physical therapy and nutrition To recognise the importance of culturally competent, multidisciplinary care including families To understand how to integrate palliative interventions in routine multidisciplinary cancer

care To recognise the difference between burnout, compassion fatigue and depression To recognise the unique aspects of end-of-life care, such as decision-making processes,

symptom management, involvement of family members and spiritual aspects To understand how to recognise pseudo-refractory symptoms and when to refer to specialist

palliative care teams for management of refractory symptoms To understand how to maintain patients’ cognition until close to death with good symptom

control To be able to assess, treat and counsel patients who are approaching end-of-life To incorporate the family and beloved ones into goal planning The curriculum also defines the required skills in dealing with the psychosocial aspects of

cancer, geriatric oncology, communication, patient education and survivorship.

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ESMO resources for integrated patient centred care educationESMO already offers a wide array of educational programmes and tools to oncologists in the domain of patient centred care. Among them (Table 4):

Table 4: ESMO resources for integrated patient centred care education

o E-learning modules44 on supportive and palliative care

o ESMO Palliative Care Fellowships 45 ESMO provides two palliative care fellowships allowing recipients observation or research at one of the ESMO Designated Centres

o ESMO Clinical Practice Guidelines 46 including guidelines on supportive care and palliative care.

o ESMO Patient Guides 47 include e.g. how to deal with side effects.

o ESMO Handbooks for physicians 48

o ESMO Academy 49 includes an overview of standards of care and future perspective in supportive care

o ESMO Preceptorships in supportive care and palliative care 50

o Oncology Pro Webcasts and Slides, Scientific Meeting Reports (using search function) http://oncologypro.esmo.org/Slide-Resources

o ESMO Congress track on supportive care and palliative care

o Core Curriculum slide sets: http://www.esmo.org/Career-Development/Global-Curriculum-in-Medical-Oncology

o ESMO collaboration with other entities with interest in supportive care and palliative care (e.g. MASCC, EAPC, ESO)

o Other resources on the ESMO website: http://www.esmo.org/Topics/Palliative-and-supportive-care

Research needs and resources in supportive and palliative careDespite growing awareness of the need to develop patient centred care and recent progress in the field, more and better scientific evidence, tailored to individual and fluctuating patient needs is required so that effective interventions can be proposed to cancer patients at each stage of their illness.

Prospective, well-designed and preferably, intervention studies are needed to evaluate the impact of palliative and supportive interventions on outcomes and QoL. Even in pain management the level of evidence in existing guidelines is low 51, 52, 53 . In this area, the ESMO-led Global Opioid Policy Initiative (GOPI) 54 seeks to drive necessary policy reform to improve severe cancer pain management and unnecessary suffering. It calls for authorities to guarantee the availability and accessibility of effective and safe pain killing treatments.

ESMO is willing to promote more research fellowships in supportive and palliative care. Research in patient-centred care should be the focus of original investigation. For anticancer treatment trials, PROs should be used together with traditional tumour oriented outcomes. It is not enough to include QoL measures in cancer clinical trials as secondary or tertiary outcomes.

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Often, only research validated by randomised clinical trials (RCTs) is considered acceptable. Nevertheless, there are methodological and ethical issues 55 linked to RCTs in palliative and end-of-life care (i.e. concerns about informed consent and the vulnerability of patients). However, recent RCTs in this setting and embedded in qualitative work showed that patients with advanced cancer benefit from participation in symptom control trials 56, 57 .

Other options include well-designed observational studies and cross-sectional surveys 58. More research is needed, for example, on short and long term side-effects of new therapeutic interventions 59; new supportive care agents; integrating new technologies such as a web-based programmes and apps for self-monitoring and reporting symptoms; congruent outcome assessments on symptoms and side effects (health care assessment versus patient reported outcomes); nutrition, physical activity, quality of life; social factors such as family issues, social support, work, financial toxicity; care giver attitudes and practices; rehabilitation and survivor care; identifying organisational, economic and other incentives for the provision of integrated and affordable patient centred care.

ESMO calls for more research to be carried out in this area in order to create the evidence needed to improve patient centred care. Furthermore, a pragmatic approach to cancer research is needed where patient centred care trials are concurrent with cancer therapy trials.

Future/VisionESMO is committed to ensuring that patient centred care is widely understood and integrated into health systems at all levels throughout the disease; that oncologists have the necessary knowledge and skills (competences) and that it is underpinned by a high level of evidence. Therefore, ESMO will advocate for

increased awareness increased research increases education increased resources to be dedicated to supportive and palliative care.

ESMO appeals to health authorities in Europe and beyond to ensure that cancer patients have equal access to the best possible patient centred cancer care that resources allow. This is a medical and ethical imperative.

ConclusionRecent studies show variable effects of the integration of early supportive and palliative care interven-tions for cancer patients and also emphasise their importance. The diverse outcomes may be partly explained by methodological challenges, i.e. different interventions, outcomes and patient populations applied in published RCTs. Manifestly, more research is needed in patient centred care.

Together with anti-cancer therapies, medical oncology should encompass patient centred care by providing supportive and palliative interventions at all stages of the disease, from the time of dia-gnosis. The oncologist’s role is not only to deliver the best quality anti-cancer treatment, but also to consider the impact of the disease and treatment on each patient’s life. Oncologists should be re -sponsible for including and collaborating with health care providers with other competences in outpa-tient and inpatient clinics in order to alleviate patients’ distress. Since only individual patient needs can determine what support is required at each stage of the disease, it is challenging to define models and standards for best patient centred care, nevertheless, interventions should be based on the best avail-able evidence.

Further research is needed to ensure that palliative and supportive interventions are evidence based and PROs should be highly encouraged. Continuing medical education (CME) is also essential for on-cologists to acquire and update the necessary skills to evaluate patients’ specific needs and provide the best care.

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ESMO is committed to ensuring that supportive and palliative care is widely understood, integrated into health systems at all levels and underpinned by evidence.

AcknowledgementThe authors thank Jackie Partarrieu from the ESMO Press Office for the editorial assistance during the preparation of the manuscript.

DisclosureKarin Jordan: Advisory board and or honoraria for presentations for Merck, MSD, Helsinn, Tesaro, Amgen, Hexal, Pfizer.Matti Aapro: Grant/Reserch supports: Amgen, Eisai, Genomic Health, Helsinn, Hospira, Novartis, Merck, Mundipharma, Pfizer, Roche, Sandoz, Tesaro,Teva, Vifor. Consultant for Amgen, BMS, Celgene, Clinigen, Eisai, Genomic Health, GSK, Helsinn, Hospira, JnJ, Novartis, Merck, Merck Serono, Mundipharma, Pfizer, Pierre Fabre, Roche, Sandoz, Tesaro,Teva, Vifor and has received honoraria for lectures at symposia ( equivalent speaker's bureau ) of Amgen, Bayer Schering, Cephalon, Chugai, Eisai, Genomic Health, GSK, Helsinn, Hospira, Ipsen, JnJ, OrthoBiotech, Kyowa Hakko Kirin, Merck, Merck Serono, Mundipharma, Novartis, Pfizer, Pierre Fabre, Roche, Sandoz, Sanofi, Tesaro, Taiho, Teva, Vifor.Stein Kaasa: Holds stocks in EIR Solutions.Carla Ida Ripamonti: Honoraria from Amgen for educational programs on ONJ.Florian Scotté: Roche, Vifor, MSD, Teva, Norgine, Prostrakan, Leo pharma, Janssen, Hospira, Boehringer, Sanofi, AMGEN, Pierre Fabre Oncologie, Tesaro.Florian Strasser: Unrestricted Industry Grants for Clinical Research (last 10 years) Celgene (Lenalidomide Cachexia trial) Fresenius (Survey parenteral nutrition malignant bowel obstruction) Helsinn (Palliative Research Centre, MENAC Trial, KSSG Cachexia) Participation in company-lead clinical cachexia trials Novartis (BYM338 cachexia trial) Punctual Advisorship (Boards, Expert Meetings) Acacia, ACRAF, Amgen, Baxter, Celgene, Danone, Fresenius, GlaxoSmithKline, Grünenthal, Helsinn, ISIS Global, Millennium/Takeda, Mundipharma, Novartis, Novelpharm, Nycomed, Obexia, Otsuka, Ono, Pharm-Olam, Pfizer, Psioxus, PrIME, Santhera, Sunstone, Teva, Vifor. Honoraria for Speaking Helsinn prIME.Annie Young: Honoraria from MSD, Helsinn, Bayer, Leo Pharma. Educational grant from Bayer.Eduardo Bruera: Research grant from Helsinn Pharma.Jørn Herrstedt: Advisory board activity Tesaro and remuneration SOBI. Dorothy Keefe: Advisory Board and stock options: Entrinsic Health Solutions. Advisory Board: Second Genome.Barry Laird: Advisory Board for Pfizer and Chugai Pharma.Declan Walsh: Non-executive Director of Nualtra.Jean-Yves Douillard: Nothing to declare.Andrés Cervantes: Advisory board and or honoraria for Amgen, Lilly, Novartis, Takeda, Roche, MerckSerono, Servier.

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Online supplement

Table 2: Potential Composition of the MDT besides Medical Oncologists

Palliative medicine specialist Oncology nurse practitioner (in countries where they are available) General practitioner Nutritionist Psycho-oncologist Social worker (financial toxicity, need for child-care, expenses such as wheelchair, etc.) Physiotherapist Pharmacist Consultants to the oncology team such as:

o Dermatologisto Cardiologist trained in cardiotoxicity of oncological treatmentso Neurologisto Pneumologisto Endocrinologisto Surgeono Radio oncologist o Nephrologisto Psychiatristo Geriatriciano Ear, nose and throat specialist (ENT)o Rheumatologisto Ophthalmologisto Fertility specialist

Allied health professionals in the community and in hospitals Care home staff Self help and support groups, patient advocacy associations Cleric (or spiritual helper) Volunteers

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15 Kavalieratos D, Corbelli J, Zhang D. et al. Association Between Palliative Care and Patient and Caregiver Outcomes. A Systematic Review and Meta-analysis. JAMA. 2016;316(20):2104-2114. doi:10.1001/jama.2016.16840.

16 Haun MW, Estel S, Rücker G, et al. Early palliative care for adults with advanced cancer. Cochrane Library, 2017. DOI: 10.1002/14651858.CD011129.pub2

17 Gaertner J, Siemens W, Meerpohl J, et al. Effect of specialist palliative care services on quality of life in adults with advanced incurable illness in hospital, hospice, or community settings: systematic review and meta-analysis.BMJ. 2017 Jul 4;357:j2925. doi: 10.1136/bmj.j2925.18 Groenvold M, Petersen MA, Damkier A, et al. Randomised Clinical Trial of Early Specialist Palliative Care Plus Standard Care Versus Standard Care Alone in Patients With Advanced Cancer: The Danish Palliative Care Trial. Palliat Med 2017 May 1:269216317705100. doi: 10.1177/0269216317705100. [Epub ahead of print].

19 Franciosi V, Caruso G, Maglietta G, et al. Palliative care evaluation of effects early palliative care on quality of life of advanced cancer patients: a multicenter controlled trial. Ann Oncol 2016;27 (suppl 6): LBA49.

20 Ripamonti C, Pessi MA, Boldini S, et al. Supportive Care in Cancer Unit (SCCU) at the NCI of Milan: A New Integrated Model of Medicine in Oncology. Current Opinion in Oncology 2012; 24: 391-6

21 Scotté F, Hervé C, Oudard S, et al. Supportive care organisation in France: an in depth study by the French speaking association for supportive care in cancer (AFSOS). Eur J Cancer. 2013 Mar;49(5):1090-6.

22 Vasile E, Lucchesi M, Ginocchi L, et al. Dedicated supportive care team at the oncology unit: a model of simultaneous care for cancer patients. Support Care Cancer 2014; 22:867-868

23 Scotté F, Herveé C, Leroy P et al. Supportive Care Organization in France: a national in-depth survey among patients and oncologists. Support Care Cancer 2017; 25: 2111-2118

24 Antonuzzo A, Vasile E, Sbrana A, et al. Impact of a supportive care service for cancer outpatients: management and reduction of hospitalizations. Preliminary results of an integrated model of care. Support Care Cancer 2017; 25:209-212

25 Ripamonti CI, Molani P, Desti C, et al. A supportive care in cancer unit reduces costs and hospitalizations for transfusions in a comprehensive cancer center. Tumori 2017; 103:449-456

26 Morin S, Leroy P, Aubaret C, et al. Cost effectiveness in a supportive care unit. J Clin Oncol 35, 2017 (suppl; ASCO) (Abstract e18326)

27 Denehy L. Intensive preoperative rehabilitation improves functional capacity and postoperative hospital length of stay in elderly patients with lung cancer [commentary]. J Physiother. 2017 Jun 17. doi: 10.1016/j.jphys.2017.05.003. [Epub ahead of print]

28 Driessen EJ, Peeters ME, Bongers BC, et al. Effects of prehabilitation and rehabilitation including a home-based component on physical fitness, adherence, treatment tolerance and recovery in patients with non-small cell lung cancer: A systematic review. Crit Rev Oncol Hematol. 2017 Jun; 114:63-76. doi: 10.1016/j.critrevonc.2017.03.031. Epub 2017 Apr 5.

29 O'Mara A, Rowland JH, Greenwell TN et al. NIH Medical Rehabilitation Coordinating Committee. National Institutes of Health Research Plan on Rehabilitation: NIH Medical Rehabilitation Coordinating Committee. Phys Ther. 2017 Apr 1;97(4):104-407. doi: 10.1093/ptj/pzx026.

30 Leensen MCJ, Groeneveld IF, Heide IV, et al. Return to work of cancer patients after a multidisciplinary intervention including occupational counselling and physical exercise in cancer patients: a prospective study in the Netherlands. BMJ Open. 2017 Jun 15;7(6): e014746. doi:10.1136/bmjopen-2016-014746.

31 Leensen MCJ, Groeneveld IF, Rejda T, et al. Feasibility of a multidisciplinary intervention to help cancer patients return to work. Eur J Cancer Care (Engl). 2017 Apr 25.doi: 10.1111/ecc.12690. [Epub ahead of print]

32 ESMO Patient Guide on Survivorship: http://www.esmo.org/content/download/117593/2061518/file/ESMO-Patient-Guide-Survivorship.pdf

33 Schrijvers D and Cherny N. ESMO Clinical Practice Guidelines on palliative care: advanced care planning. Ann Oncol (2014) 25 (suppl 3): iii138-iii142.

34 End of life care. NHS. http://www.nhs.uk/Planners/end-of-life-care/Pages/what-is-end-of-life-care.aspx

35 Care of adults in the last days of life. NICE guideline. December 2015. https://www.nice.org.uk/guidance/ng31/resources/care-of-dying-adults-in-the-last-days-of-life-pdf-1837387324357

36 End of life care. NHS. http://www.nhs.uk/Planners/end-of-life-care/Pages/what-is-end-of-life-care.aspx

37 Scotté F, Herveé C, Leroy P, et al. Supportive Care Organization in France: a national in-depth survey among patients and oncologists. Support Care Cancer 2017; 25: 2111-2118

38Hui D. Bruera E. Integrating palliative care into the trajectory of cancer care. Nat Rev Clin Oncol. Published online 2015 Nov 24. doi: 10.1038/nrclinonc.2015.201

39 Hui D, Bansal S, Strasser F, Morita T, et al. Indicators of integration of oncology and palliative care programs: an international consensus. Ann Oncol. 2015 Sep;26(9):1953-9.

40 The ESMO Designated Centres of Integrated Oncology and Palliative Care accreditation programme

http://www.esmo.org/Patients/Designated-Centres-of-Integrated-Oncology-and-Palliative-Care

41 Hui D, Cherny N, Latino N, Strasser F. The 'critical mass' survey of palliative care programme at ESMO designated centres of integrated oncology and palliative care. Ann Oncol. 2017 Sep 1;28(9):2057-2066.

42 http://www.esmo.org/Patients/Apply-to-Become-an-ESMO-Designated-Centre

43 Recommendations for a Global Curriculum in Medical Oncology http://www.esmo.org/Career-Development/Global-Curriculum-in-Medical-Oncology

44 ESMO e-learning: http://oncologypro.esmo.org/Science-Education/ESMO-E-Learning-and-V-Learning

45 ESMO Fellowships: http://www.esmo.org/Career-Development/Oncology-Fellowships/Awardees-and-Reports/Palliative-Care-Fellowship-Reports

46 ESMO Guidelines on Supportive Care: http://www.esmo.org/Guidelines/Supportive-Care

47 ESMO Patient Guides : http://www.esmo.org/Patients/Patient-Guides and ESMO Guide for Patients with Advanced Cancer http://www.esmo.org/content/download/6932/132781/file/ESMO-A-Guide-for-Patients-with-Advanced-Cancer.pdf

48 ESMO Handbooks

I. http://oncologypro.esmo.org/Publications/Handbooks/Nutrition-and-Cancer

II. http://oncologypro.esmo.org/Publications/Handbooks/Advanced-Cancer-Care

III. http://oncologypro.esmo.org/Publications/Handbooks/Rehabilitation-Issues-During-Cancer-Treatment-and- Follow-Up

49 ESMO Academy: http://www.esmo.org/Conferences/ESMO-Academy-2017/Programme

50 ESMO Preceptorship. Slides from the 2017 preceptorship on supportive and palliative care

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51 Caraceni A, Hanks G, Kaasa S, et al. Use of opioid analgesics in the treatment of cancer pain: evidence-based recommendations from the EAPC. Lancet Oncol. 2012 Feb;13(2):e58-68. doi: 10.1016/S1470-2045(12)70040-2.

52 Ripamonti CI, Bossi P, Santini D, Fallon M. Pain related to cancer treatments and diagnostic procedures: a no man’s land? Ann Oncol. 2014 Jun;25(6):1097-106. doi: 10.1093/annonc/mdu011. Epub 2014 Mar 13. Review.

53 Bandieri E, Romero M, Ripamonti CI, et al. Randomized trial of low-dose morphine versus weak opioids in moderate cancer pain. J Clin Oncol. 2016 Feb 10;34(5):436-42. doi: 10.1200/JCO.2015.61.0733. Epub 2015 Dec

54 ESMO-led Global Opioid Policy Initiative (GOPI) http://www.esmo.org/Policy/Global-Opioid-Policy-Initiative

55Hanks G. Ethical issues in palliative care research. The Oxford Textbook of Palliative Medicine. eds., 2010

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56 Fallon M, Hoskin PJ, Colvin LA et al, Randomized Double-Blind Trial of Pregabalin Versus Placebo in Conjunction With Palliative Radiotherapy for Cancer-Induced Bone Pain. Journal of Clinical Oncology 2016 34:6, 550-556

57 Solheim TA, Laird BJA, Balstad TR, et al, A randomised phase II trial of a multimodal intervention for the management of cachexia in lung and pancreatic cancer – J Cachexia, Sarcopenia and Muscle 2017. doi: 10.1002/jcsm.12201. [Epub ahead of print]

58Middlemiss T, Lloyd-Williams M, Laird BJ, et al. Symptom control trials in patients with advanced cancer: A qualitat-ive study. 50 (5), 642-649. Journal of Pain and Symptom Management. doi.org/10.1016/j.jpainsymman.2015.05.009http://www.sciencedirect.com/science/article/pii/S0885392415002547

59 A Beginners Guide to Successful Palliative Care. Scottish Partnership for Palliative Care. Section 5: Identifying potentially useful ideas for research https://www.palliativecarescotland.org.uk/content/publications/1340288254_A-Beginners-Guide-to-Successful-Palliative-Care-Research-.pdf