' AgeCare - Academy of Geriatric Cancer Research

The incidence of cancer is increasing rapidly in Denmark as in most parts of the world, the main reason being the increasing longevity of the population, the so called demographic effect. In Denmark, the annual number of new cancers is expected to increase from about 38,000 in 2015 to over 45,000 in 2030, almost 70% being over 65 years at diagnosis. Elderly cancer patients constitute an inhomogeneous group, some being fit and some frail, mostly due to varying degrees of comorbidity. In general, there is still lack of knowledge about treatment of older cancer patients and lack of national as well as international consensus on guidelines for their treatment.

Other treatments 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. 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.

Academy of Geriatric Cancer Research (AgeCare) was officially nominated an Elite Research Center at Odense University Hospital (OUH) in December 2013 for a five-year period, 2014-2018, with the overall aim of optimizing cancer therapy and supportive care in older cancer patients. By the end of 2018, AgeCare had delivered >70 peer-reviewed publications, initiated 16 PhD-studies, and obtained external funding of DKK 29 mio. Based on the results obtained by the AgeCare Elite Research Center in the first five-year period the center was in 2018 awarded funding for a second five-year period, 2019-2023.

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.

The first five years of AgeCare sparked a very strong interest in geriatric oncology among several of our PhD-students. They have presented their work at the annual conferences of the International Society of Geriatric Oncology (SIOG). In September 2018, doctor Trine Lembrecht Jørgensen received a grant from the Danish Comprehensive Cancer Center (DCCC) to establish a network, a national forum of interest for geriatric oncology. The national network: DCCC-AGE has met twice a year.

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.

Work packages

WP1: Epidemiology and genetic epidemiology of cancer in the elderly

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.

WP2: Cancer biology and molecular biomarkers associated with altered disease and treatment-outcomes in elderly patients

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.

WP3: 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.

WP4: 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.

WP5: 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.

WP6: Personalized supportive care for older patients with cancer

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. Further, 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.