' AgeCare - Academy of Geriatric Cancer Research

Aim and idea of the Centre                                                                     

In 2010, 35,563 persons were diagnosed with cancer in Denmark of whom 45% of men and 41% of women were aged 70+ years. This proportion will increase markedly over the next years, primarily because of the aging population. Our knowledge of elderly cancer patients’ tolerance to and benefit from antineoplastic treatment is sparse due to underrepresentation of this patient group in clinical trials. In the period from 2007 to June 2010, 24 drugs were approved by FDA for the treatment of cancer, and only 33% of patients included in the registration trials were age 65 years or older compared to 59% of the US cancer population aged 65 years or older [1]. It is unethical to suggest evidence-based antineoplastic therapy based on chronologic age alone. Because clinical trials primarily include younger more fit patients, such results may not be applicable to the elderly without additional risk assessment. Elderly patients often suffer from reduced organ function (kidney, liver, bone marrow) and one or more comorbid conditions, factors that can impair the tolerability of antineoplastic treatment. In addition some have cognitive dysfunctions resulting in difficulties in complying with the recommended treatment. At the time of diagnosis, the mean number of drugs used by 70+ year-old Danish cancer patients is 4,6, a number that increases when antineoplastic therapy is initiated and supportive care drugs are needed as well. This constitutes a high risk of adverse effects due to drug-drug interactions.   
 
Internationally, there is a rapidly growing appreciation of the need for specific strategies in the management of elderly cancer patients. The International Society of Geriatric Oncology (SIOG) was founded in 2000 and the Journal of Geriatric Oncology in 2010. SIOG has recently (2011) defined the 10 most important initiatives in geriatric oncology. In addition to education and clinical practice, four of these initiatives are related to research. In the US, the Cancer and Aging Research Group (www.mycarg.org), the National Cancer Institute (www.cancer.gov) and the National Institute on Aging (www.nia.nih.gov) have planned three conferences (from 2010-2015), to identify the knowledge gaps in geriatric oncology and to propose research methods and strategies to fill these gaps. The conclusions of the first conference were published in March 2012 [2] and emphasized that future oncology research in older adults should focus on 1) improved standardized geriatric assessments, 2) substantially enhanced biological assessments, 3) specific trials for the elderly and most vulnerable patients, and 4) research infrastructure specifically targeting older adults and substantially strengthened geriatrics and oncology research collaborations. In the UK, a recent report concluded that there is a strong need for specific assessment methods and identification and management of comorbidity in older cancer patients. Consequently the Macmillan Cancer Support, Age UK and the Department of Health have initiated 5 pilot projects testing new methods for assessment of older people with cancer [3].

In Denmark, there is no national strategy for the management of elderly cancer patients, and current treatment decisions are primarily based on chronologic age and insufficient evaluations of functional levels, such as scoring of ECOG performance status. In addition, since we are currently unable to accurately predict the efficacy of antineoplastic therapy in the elderly, some will not receive treatment while others will be offered treatment despite the potential lack of any benefit. The failure to address the need for a national strategy could have a fundamental impact on the sustainability of the health care system.

At Odense University Hospital, all cancer patients are evaluated by multidisciplinary teams (MDT) including not only the different specialties involved in the clinical management of cancer patients but also a multidisciplinary research organization encompassing all aspects from molecular and genetic science to the clinical palliation of terminal cancer patients.

Patient selection and individually tailored treatment strategies are potential key points in improving survival and minimizing toxicity of treatment, especially in elderly patients. To accomplish this, we need specific and individual mapping regarding details of several disease characteristics in each patient. Ideally, this mapping should cover identification of pre-therapeutic molecular biomarkers and their prognostic and predictive value. In combination with detailed staging at diagnosis and evaluation of clinical baseline characteristics, this multidisciplinary approach will allow a treatment plan tailored to each patient. 

Translational research is an important new area in cancer research giving insight into molecular mechanisms underlying clinical conditions. The field of cancer in the elderly has only been slightly addressed by translational researchers, although it seems evident that the biology of cancer cells and the surrounding normal cells in the elderly is significantly altered. These factors need to be further investigated and might become important in future treatment strategies for elderly cancer patients.

The proposed research centre acknowledges that the time has come for oncologists, geriatricians, surgeons and other related health care professionals as well as translational scientists to work together to focus on individualized management of older cancer patients to improve treatment and care

 

Aim of AgeCare
To optimize cancer therapy and supportive care in older cancer patients.

 

Scientific Content of AgeCare

  • Epidemiological and biodemographic research in elderly focusing cancer and aging.Biological assessment of older patients including pharmacokinetics and pharmacodynamics
  • Identification of biomarkers associated with altered disease-outcome in elderly patients. 
  • Development of geriatric assessment tools to distinguish between elderly cancer patients who will and who will not benefit from treatment.
  • Performance of clinical trials assessing treatment benefits in older cancer patients.
  • Performance of clinical trials particularly addressing treatment benefits and limitations in older cancer patients with comorbidity.
  • Assessment and prevention of side and late effects in older cancer patients. 
  • Development of specific upfront rehabilitation plans for older cancer patients.
  • Explore the need for specific supportive care interventions in older cancer patients.

 

Scientific Staff

AgeCare will include physicians, representing several specialties (oncology, hematology, surgery, gynecology, pathology, geriatric and respiratory medicine) medical physicists and nurses. Collaborations have been agreed with translational researchers, molecular biologists and clinical pharmacologists at the University of Southern Denmark. Significant national and international collaboration has been confirmed.

Existing staff
The Clinical Research Unit, Department of Oncology: 14 research nurses, 3 research secretaries, 1 data manager, 15 Ph.D. students and 5 post docs. The unit manages 50-60 clinical trials. AgeCare will furthermore include a large number of clinical and laboratory Departments, OUH as well as cancer researchers at the Department of Cancer and Inflammation Research, SDU. The total number of current PhD students in the proposed Elite Research Center exceeds 50.

 
   

Work package leaders 

WP1                                  
Kaare Christensen MD, DMSc, Professor, Head of Research, Epidemiology Section, SDU, Consultant, Departments of Clinical Genetics, Clinical Biochemistry and Pharmacology. Director, Danish Aging Research Center and the Danish Twin Registry. Senior Research Scientist, Sanford Institute, Duke University, USA and 340+ publications.

Henrik Frederiksen MD, PhD, Consultant, Department of Haematology, OUH. 15+ years of experience in epidemiology. PhD focused on physical functioning among elderly. Main research area is clinical epidemiology of haematological malignancies. Head of the National Haematological Danish Multidisciplinary Cancer Group (DMCG).

WP2                                 
Henrik Ditzel MD, DMSc, Head of Research, Department of Cancer and Inflammation Research, SDU, Consultant, Department of Oncology, OUH. Adjunct Professor, Scripps Research Institute, CA, USA and Director of the Bioimaging Center DAMBic at OUH/SDU. 20+ years experience in translational cancer research (80 publications).

WP3                                 
Lars Lund MD, DMSc, Professor, Head of Research in Urology, SDU and Consultant, Department of Urology, OUH. Member of the DMCG in renal cancer. Connected to Vanderbilt University, Tennessee in 2006/7 and performing research in comorbidity and urological cancers, 120 publications.

WP4            
Olfred Hansen MD, PhD, Consultant, 20+ years of experience in the treatment of lung cancer. Head of the Radiotherapy Unit,  OUH and Associate Professor at the Institute of Clinical Research, SDU.  

Carsten Brink, Medical Physicist, PhD, Associate Professor in Radiation Physics, SDU and Assistant Chief Physicist at the Laboratory of Radiation Physics, OUH. Main research area is related to extraction of toxicity and tumor response from daily imaging modalities.

WP5                                 
Per Pfeiffer MD, PhD, Professor, 20+ years experience in clinical oncology. Research areas, clinical and translational research in GI cancer (100+ publications). Head of the Danish Colorectal Oncology Group and member of the Nordic Biomodulating Group.

Niels Abildgaard MD, DMSc, Professor of Hematology and Head of the Research Unit at the Department of Haematology. 20+ years of experience with clinical studies in hematological disease (60 publications in this field). Chairman of the Danish and of the Nordic Myeloma Study Groups.

WP6                                 
Jørn Herrstedt MD, DMSc, Professor, Head of Research at the Department of Oncology. Past President, Multinational Association of Supportive Care in Cancer. Board member, Nordic Society of Gynecologic Oncology. Twenty-five years experience in oncology (100+ publications).

Lars Erik Matzen MD, Head, Department of Geriatric Medicine and of the Geriatric Research Unit.     Well-established international research collaboration in Geriatric Medicine. Author or co-author of 40 peer-reviewed publications in geriatric medicine.

WP7                                 
Niels Christian Hvidt ThD, Associate Professor, born 1969, is a Danish theologian and humanistic health researcher, trained in Copenhagen and Rome, who since 2006 has worked as an associate professor at the Institute of Public Health at University of Southern Denmark, presently at the Research Unit of General Practice. Hvidt was professor for Spiritual Care (50%) at Ludwig Maximilian University and External Research Fellow at Freiburg Institute for Advanced Studies (FRIAS). Hvidt’s researcher areas include Spirituality and Health, Spiritual Care and Patient Perspectives (100+ publications). Hvidt serves as initiator and advisor of various research networks and knowledge centers and is considered as the initiator of research in spirituality and health as a new strategic research field in Denmark.

Karin B. Dieperink, RN, MCN, PhD. Post doc at Department of Oncology, Academy of Geriatric Cancer Research (AgeCare), and Danish Knowledge Centre of Rehabilitation and Palliative Care (REHPA). Research interest is within nursing, rehabilitation, palliation and supportive care for cancer patients and their families. The research area is concerning cancer patients’ side effects and late adverse effects after treatment, quality of life and coping with the life situation and rehabilitation for prevention or reducing late adverse effects, furthermore, uncovering the impact of disease on family health and intervention with family nursing. Initiator of the Danish Research Network for Cancer Nurses.

 
   

Danish collaborative partners

Odense University Hospital (OUH)

Clinical Oncology
Jørgen Johansen Consultant, MD, PhD
Jesper Grau Eriksen Consultant, MD, PhD
Trine Lembrecht Jørgensen MD, PhD

Pathology
Martin Bak Head of Department, Pathology, MD
Doris Schledermann Consultant, MD
Anne Marie Bak Jylling, Consultant, MD
Niels Marcussen Professor, MD, DMSci
Bjarne Winther Kristensen, Professor MD, PhD
Michael Boe Møller Consultant, MD, DMSci

Gynecology
Ole Mogensen Professor, MD, DMSci

Surgery
Niels Quist Professor, MD, DMSci, Abdominal Surgery
Michael Bau Mortensen, Professor, MD, PhD, Abdominal Surgery
Gunnar Baatrup Professor MD, DMSci, Abdominal Surgery
Jens Ahm Sørensen, Consultant PhD, Plastic Surgery
Katrine Søe, Consultant MD, Plastic Surgery
Peter Licht, Professor, MD, PhD, Thoracic Surgery
Christian Godballe, Professor, MD, PhD, Head and Neck Surgery.

Medicine
Pernille Hermann Consultant MD, PhD, Endocrinology
Hanne Vestergaard Head of Department, Hematology, MD, PhD
Thomas Stauffer Larsen Consultant, MD, PhD, Hematology.

Nursing and Rehabilitation
Karin Dieperink RN, MSc, PhD, Oncology
Hanne Kaa Kristensen Research Therapist, Rehabilitation.

University of Southern Denmark (SDU)
Kim Brøsen Professor, MD, DMSci, Clinical Pharmacology
Martin Røssel Larsen Professor, MSc, PhD, Faculty of Natural Sciences
Dorte Gilså Hansen MD, PhD, Head National Center for Research in Cancer Rehabilitation
Axel Skytthe PhD, Senior Data Analyst, the Danish Twin Registry/Institute of Public Health
Birte Østergaard RN, MSc, PhD, Research Unit of Nursing
Rikke Leth-Larsen Associate Professor, PhD, Cancer and Inflammation Research
Morten Gjerstorff Associate Professor, PhD, Cancer and Inflammation Research.

National collaborators
Cai Grau Professor MD, DMSci, Clinical Oncology, Aarhus University Hospital
Christoffer Johansen Professor MD, DMSci, Danish Cancer Society
Hans Storm MD, Director, Danish Cancer Society
Gerda Engholm, Senior Statistician, Danish Cancer Society
Nils Brünner Professor MD, DMSci, Faculty of Health/Medical Sciences University of Copenhagen
Bente A. Esbensen RN, PhD, Research Unit, Nursing and Health Science, Glostrup University Hospital
Dorte L. Nielsen Professor MD, PhD, DMSci, Clinical Oncology, Herlev Hospital
Finn Rønholt Head of the Department of Geriatric Medicine, MD, PhD, MPA, Herlev Hospital
Tove Lindhardt Senior Researcher, RN, MSc, Dr.Med.Sci, Department of Geriatric Medicine, Herlev Hospital
Julia S. Johansen, Professor, MD, Dr.Med.Sci, Clinical Oncology, Herlev Hospital
Nessn H Azawi MD, Consultant, Urology, Roskilde Hospital.

 

International high-level researchers

WP1
Lorelei Mucci, Associate Professor of Epidemiology, Harvard School of Public Health, Co-leader Cancer Epidemiology Program, Dana Farber Cancer Center, Boston, USA.
Jaakko Kaprio PhD, Professor, Department of Mental Health, National Institute for Health and Welfare and Professor of Genetic Epidemiology, University of Helsinki, Finland.

WP2
Jun Wang, Professor of Genomics and Biostatistics, Head of Beijing Genome Institute, China.

WP3
Peter E Clark MD,BA, Ass. Prof. Urologic Surgery, Vanderbilt University, Nashville, USA.
Milad Hanna MD, Consultant, Imperial Trust Hospital, London, UK.

WP4
Søren M. Bentzen, PhD, DSc, Professor of Human Oncology and Leader of the Imaging and  Radiation Science Program of the Carbone Comprehensive Cancer Center at the University of Wisconsin School of Medicine and Public Health, Wisconsin, USA.
David Ian Thwaites, Professor of Medical Physics, University of Sydney, Australia.

WP5
Matti Aapro MD, Head of Oncology Center, Clinic de Genolier, Geneva, Switzerland.
Eric Pujade-Lauraine, Professor in Oncology, PhD, Head of the Medical Oncology Department, Hôpital Hôtel-Dieu, Paris, France.
Halfdan Sørbye MD, PhD, Professor in Oncology, Haukeland University, Bergen, and
Consultant, Department of Oncology Haukeland University Hospital, Bergen, Norway.
Anders Waage MD, Dr.Med.Sci, Consultant/Professor, St. Olavs University Hospital, Norway.

WP6
Tahir Masud MD, Professor and Consultant Physician in General and Geriatric Medicine,
City Hospital NHS Trust, Nottingham, UK.
Arti Hurria MD, Associate Professor, City of Hope National Medical Center, CA, USA.            

WP7
Sarah Darby Professor of Medical Statistics, University of Oxford, UK.
Eduardo Bruera Professor, MD, Chair of the Department of Palliative Care and Rehabilitation
Medicine, MD Anderson Cancer Center, Houston, USA. 
Romy Mahrer-Imhof RN, Dr Phil, Professor Zürich University, Winterthur, Switzerland.
Marcia van Rieper, RN, Professor, PhD, University of North Carolina, Chapel Hill, USA.
Elisabeth Coyne, RN, Senior Lecturer, PhD, Logan Campus Griffith University, Australia.

 

Advisory board

Professor Riccardo Audisio, UK.

Professor Mario Dicato, Luxembourg

Professor Dorothy Keefe, Australia

Professor Philip Poortmans, The Netherlands

Professor Daniel F Hayes, USA

 

   

Work packages  

WP 1 Epidemiology
This WP will include five major research lines. 1) Age-trajectory of mortality and cancer. 2) Comorbidity in elderly patients with lymphoid malignancies. 3) Hereditability of various cancer forms with a special focus on the age-dependency of the genetics influence. 4) Prenatal hormonal influence on late-life cancer forms and 5) Interaction between cancer risk and longevity.

WP 2 Biomarkers
Identification of biological alterations associated with elderly patients, including differences in cancer stem cell biology. Identification of biomarkers associated with altered disease-outcome in patients with increased age, using a panel of global analysis including proteomics, next-generation sequencing, gene array and cellular and small animal bioimaging.

WP 3  Surgery
Five surgical specialities will focus on new treatment modalities and outcomes. Five areas of research related to cancer in the elderly: 1) Minimal invasive surgery, fast track. 2) Robot surgery in different cancer forms. 3) Cryo-therapy for different tumours and the use of this modality in the palliative setting. 4) Imaging in elderly patients. 5) Preserving of kidney function.

WP 4 Radiotherapy
A number of trials will investigate 1) Risk of recurrence following curative intended radiotherapy in younger versus elderly cancer patients. 2) Radiotherapy-induced side effects in  elderly cancer patients with one or more comorbid conditions. 3) The use of image-guided radiotherapy (IGRT) in elderly cancer patients who receive radiotherapy with a curative intent.   

WP 5  Medical cancer treatment
A number of phase I and II trials comprising different disease groups (lung, GI cancer, gynecologic, urologic, hematologic, breast and head and neck cancer) will be designed specifically for elderly cancer patients. These will investigate 1) Dose response of chemotherapy in elderly cancer patients. 2) Tolerability. 3) Outcome in elderly cancer patients based on subgroups of regional and national registries. 4) Pharmacokinetics and pharmacogenetics.

WP 6 Supportive Care - focusing comorbidity
This WP will use comprehensive geriatric assessment (CGA) and address comorbidity focusing 1) Mapping of comorbidity in elderly cancer patients in the  Region of Southern Denmark. 2) Preoperative CGA and interventions if needed to decrease postoperative complications and mortality. 3) Pre-chemotherapeutic CGA and interventions if needed to improve outcome of first line treatment in elderly cancer patients. 4) Pre-chemotherapeutic CGA and the ability to predict outcomes in elderly cancer patients with recurrent disease.

WP 7  Supportive Care – focusing cancer disease-related complications and treatment-induced adverse effects
Identification of late adverse effects of particular relevance to older cancer patients, e.g. bone complications. A possible relationship between side effects and pharmacokinetics and pharmacogenetics will be investigated. Rehabilitation will be another focus area. A PhD study on rehabilitation and intervention will be completed late 2013 and subsequent studies will focus on group interventions to strengthen patients' self-management and self-efficacy.

 
   
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Overview of work  packages*  
   
WP WP subject WP leader Numbers of
ph.d.-students
Number of
post docs
Number of
publications
WP1

Epidemiology

Kaare Christensen, Henrik Frederiksen

2 1 10
WP2

Biology and molecular biomarkers

Henrik Ditzel

2 2 12
WP3

Surgery

Lars Lund

2 1 12
WP4

Radiation therapy

Olfred Hansen, Carsten Brink

2 3 15
WP5

Medical treatment

Per Pfeiffer, Niels Abildgaard

3 2 18
WP6

Supportive care I

Jørn Herrstedt, Lars Erik Matzen

2 1 8
WP7

Supportive care II

Marianne Ewertz, Lis Wagner

3 1 10
Total     16 11 85
 

*All figures indicate the expected outcome 2014-2018.