Short summary

Older patients with non-small cell lung cancer (NSCLC) treated with stereotactic body radiation therapy (SBRT) often die from other causes than lung cancer due to age-related comorbidities. This national randomized study will include 130 patients throughout 5 Danish cancer centres and investigate if a comprehensive geriatric intervention (CGA) when added upfront to SBRT for patients with localized NSCLC will have an impact on quality of life (QoL), overall survival, physical functionality and unplanned hospital admissions. If an upfront CGA improves patients' general health status, this study could lead to implementation of a CGA in standard clinical practice as well as further research on older patients receiving radiotherapy.

Rationale

Lung cancer is a frequent type of malignant disease with 4,600 patients diagnosed every year in Denmark. It is estimated that approximately 50% of newly diagnosed cases occur in patients older than 70 years of age. These patients often have significant comorbidities mainly because of smoking, but also because of advances age at the time of diagnosis. In general, older patients with cancer have been underrepresented in clinical trials. As such, treatment of this group of patients represents a unique challenge since knowledge of older patients' tolerance to and benefit of cancer treatment is limited. Approximately 85% of all lung cancers are NSCLC. Lung cancer has a poor prognosis with an overall 5-year survival of approximately 15%. However, 25% of patients with NSCLC are diagnosed at an early stage and thus have a chance at being cured. Historically, the gold standard of treatments for patients with localized NSCLC has been lobectomy. However, some older patients are considered medically inoperable due to multimorbidity or they simply refuse surgery, and adjustment of treatment must be done according to the patients' health condition. During the past decades, SBRT has emerged as an alternative to surgery, showing comparable local control of the tumour with fewer people experiencing complications or toxicity. SBRT is a high precision hypo-fractionated treatment of tumors located outside the brain, involving extremely precise delivery of very intense doses of radiation to the tumor, while sparing the surrounding normal tissue. Danish data from the Department of Oncology, OUH, showed a 5-year overall survival at 35-40% for patients treated with SBRT compared with 6% in an untreated group. However, data also indicated that many of the lung cancer patients treated with SBRT die of other causes than lung cancer, probably due to age-related comorbidity. The general population is aging, and more patients are expected to suffer from comorbidites that will impact mortality. However, ageing is a heterogenous process and patients within the same chronological age group may reflect differen physiological ages. The International Society of Geriatric Oncology (SIOG) recommend performin a CGA in older patients with cancer to optimize the individual patient's general health status. The CGA was developed by geriatricians as a multidimensional interdisciplinary diagnostic process focused on determining frailty of an older person in order to develop a care plan for treatment and long-term follow-up. It consists of different domains of medical, functional, cognitive and social assessment, including medical history and physical examination with the potential to guide targeted interventions which could improve the older cancer patients' general health status. All domains are assessed with different validated instruments. A CGA identifies important deficits in the older cancer population and is considered a better assessment for predicting tolerance for cancer treatment than the performance status frequently used by oncologists. Improved survival and a decreased need for hospital admission has been demonstrated in older patients with non-malignant diseases who had undergone a CGA. A randomized pilot study at OUH investigated the impact of CGA in patients with localized NSCLC treated with SBRT. Indication of a small differences in quality of life and overall survival in favour of patients who recieved CGA were found, however such differences can only be validated in a larger study. This national randomized study aims to investigate if a CGA when added upfront to SBRT for patients with localized NSCLC will have an impact on QoL, overall survival, physical functionality and unplanned admissions to hospital. Improving the general health status of older patients with localized NSCLC through a CGA might lead to improved quality of life and overall survival.

Description of the cohort

This is a national randomized study of all patients >70 years of age diagnosed with T1-3N0M0 NSCLC, considered medically inoperable at a multidisciplinary setting and therefore candidates for SBRT at Odense University Hospital, Vejle Hospital, Aarhus University Hospital, Aalborg University Hospital and Rigshospitalet. Patients will be allocated 1:1, one group of patients recieve CGA and the other group does not. Both groups will receive standard best practice treatment.

Data and biological material

EuroQol-5D (EQ-5D 5L) Questionnaire will be distributed * Prior to start of SBRT * 3, 6, 9 and 12 months after SBRT

Collaborating researchers and departments

Department of Oncology, Odense University Hospital

• Associate Professor Stefan Starup Jeppesen, MD, PhD
• Professor Olfred Hansen, MD, PhD
• Professor Carsten Brink, Medical Physicist

Department of Geriatric Medicine, Odense University Hospital

• Associate Professor Jesper Ryg, MD, PhD

Department of Oncology, Vejle Hospital

• Charlotte Kristiansen, MD

Department of Geriatric Medicine, Kolding Hospital

• Lisbeth Fredholm, MD

Department of Oncology, Rigshospitalet, Denmark

• Mette Poehl, MD, PhD

Department of Geriatric Medicine, Herlev Hospital

• Cecilia Lund, MD, PhD

Department of Oncology, Aarhus University Hospital

• Azza Ahmed Khalil, MD, PhD
• Marianne Marquard Knap, MD, PhD

Department of Geriatric Medicine, Aarhus University Hospital

• Marianne Ørum, MD, PhD

Department of Oncology, Aalborg University Hospital

• Rasmus Kjeldsen, MD
• Svetlana Kunwald, MD, PhD

Publications associated with the project

Jeppesen SS, Matzen LE, Brink C, Bliucukiene R, Kasch S, Schytte T, et al. Impact of comprehensive geriatric assessment on quality of life, overall survival, and unplanned admission in patients with non-small cell lung cancer treated with stereotactic body radiotherapy. J Geriatr Oncol. 2018;9(6):575-82.