High Intensity Aerobic exercise training and Immune cell Mobilization in patients with lung cancer (HI AIM)-a randomized controlled trial.

BACKGROUND: The increasing role of exercise training in cancer care is built on evidence that exercise can reduce side effects of treatment, improve physical functioning and quality of life. We and others have shown in mouse tumor models, that exercise leads to an adrenalin-mediated increased influx of T and NK cells into the tumor, altering the tumor microenvironment (TME) and leading to reduced tumor growth. These data suggest that exercise could improve immune responses against cancer cells by increase immune cell infiltration to the tumor and potentially having an impact on disease progression. Additionally, there are data to suggest that infiltration of T and NK cells into the TME is correlates with response to immune checkpoint inhibitors in patients. We have therefore initiated the clinical trial HI AIM, to investigate if high intensity exercise can mobilize and increase infiltration of immune cells in the TME in patients with lung cancer. METHODS: HI AIM (NCT04263467) is a randomized controlled trial (70 patients, 1:1) for patients with non-small cell lung cancer. Patients in the treatment arm, receive an exercise-intervention consisting of supervised and group-based exercise training, comprising primarily intermediate to high intensity interval training three times per week over 6 weeks. All patients will also receive standard oncological treatments; checkpoint inhibitors, checkpoint inhibitors combined with chemotherapy or oncological surveillance. Blood samples and biopsies (ultrasound guided), harvested before, during and after the 6-week training program, will form basis for immunological measurements of an array of immune cells and markers. Primary outcome is circulating NK cells. Secondary outcome is other circulating immune cells, infiltration of immune cells in tumor, inflammatory markers, aerobic capacity measured by VO2 max test, physical activity levels and quality of life measured by questionnaires, and clinical outcomes. DISCUSSION: To our knowledge, HI AIM is the first project to combine supervised and monitored exercise in patients with lung cancer, with rigorous analyses of immune and cancer cell markers over the course of the trial. Data from the trial can potentially support exercise as a tool to mobilize cells of the immune system, which in turn could potentiate the effect of immunotherapy. TRIAL REGISTRATION: The study was prospectively registered at ClinicalTrials.gov on February 10th 2020, ID: NCT04263467. https://clinicaltrials.gov/ct2/show/NCT04263467.

The effect of geriatric intervention in frail older patients receiving chemotherapy for colorectal cancer: a randomised trial (GERICO).

BACKGROUND: Older patients with colorectal cancer (CRC) experience chemotherapy dose reductions or discontinuation. Comprehensive geriatric assessment (CGA) predicts survival and chemotherapy completion in patients with cancer, but the benefit of geriatric interventions remains unexplored. METHODS: The GERICO study is a randomised Phase 3 trial including patients ≥70 years receiving adjuvant or first-line palliative chemotherapy for CRC. Vulnerable patients (G8 questionnaire ≤14 points) were randomised 1:1 to CGA-based interventions or standard care, along with guideline-based chemotherapy. The primary outcome was chemotherapy completion without dose reductions or delays. Secondary outcomes were toxicity, survival and quality of life (QoL). RESULTS: Of 142 patients, 58% received adjuvant and 42% received first-line palliative chemotherapy. Interventions included medication changes (62%), nutritional therapy (51%) and physiotherapy (39%). More interventional patients completed scheduled chemotherapy compared with controls (45% vs. 28%, P = 0.0366). Severe toxicity occurred in 39% of controls and 28% of interventional patients (P = 0.156). QoL improved in interventional patients compared with controls with the decreased burden of illness (P = 0.048) and improved mobility (P = 0.008). CONCLUSION: Geriatric interventions compared with standard care increased the number of older, vulnerable patients with CRC completing adjuvant chemotherapy, and may improve the burden of illness and mobility. TRIAL REGISTRATION: ClinicalTrials.gov ID: NCT02748811.

Physical exercise program to older frail patients receiving chemotherapy for colorectal cancer - feasibility and experiences from the GERICO study.

INTRODUCTION: Older and frail patients with cancer are at high risk of physical and functional decline during chemotherapy. Exercise interventions can often counteract chemotherapy related toxicity and may help patients to improve or retain physical function and quality of life. Studies evaluating feasibility and the effect of exercise in older patients are lacking. The aim of this study was to investigate the feasibility and effect of an exercise intervention in older frail patients during chemotherapy for colorectal cancer (CRC). MATERIALS AND METHODS: This is a secondary analysis from the GERICO study investigating the effect of geriatric interventions in frail patients ≥70 years receiving chemotherapy for CRC. All patients in the present analysis were patients randomized to geriatric interventions and who were found physically frail (low handgrip strength or slow 10 m gait speed) and therefore offered referral to the exercise program for twelve weeks. We evaluated reasons for dropping out and feasibility of an individually tailored exercise program twice a week for twelve weeks. Each 60 min session comprised warm-up followed by progressive resistance training and cool-down followed by an oral protein supplement. Baseline characteristics and the effect of exercise for patients with high and low adherence (attendance of <50% of exercise sessions) were compared. RESULTS: Of 71 patients in the intervention group, 47 (66%) were found physically frail and were offered referral to the exercise program. Seven patients were referred to municipal physiotherapy before study start. In the remaining population (N = 40) 19 had exercise adherence >50% and 21 had no or low exercise adherence. Baseline characteristics were similar between patients with high and low/no adherence, except for sex (68% and 33% were men in high and low/ no adherence group, respectively). Patients with >50% attendance had significant improvements in physical tests after twelve weeks of exercise. DISCUSSION: Low adherence to the exercise program was seen due to lack of energy and/or treatment related adverse events. Patients with high adherence benefitted from exercise during chemotherapy but did not differ from patients with low adherence at baseline. Consequently, exercise should be offered to all older frail patients receiving chemotherapy for CRC.