EXERCISE AND THE IMMUNE RESPONSE IN LUNG CANCER

Lung cancer is the number one cause of cancer-related deaths worldwide. A few decades ago, the prognosis at lung cancer first diagnosis was generally poor with only a few months of median survival. New treatment regimens have markedly improved survival times - especially in certain histologic and molecular pathologic subtypes. The positive effect of exercise on the incidence of several cancer entities such as colorectal- or breast cancer, has been demonstrated previously. Physically active individuals are diagnosed with cancer significantly less often as compared to sedentary people. In oncologic follow-up care, a positive effect of exercise and training with an advantage in survival has also been proven, e.g. in breast cancer patients.

In addition, existing data shows a positive effect of exercise on the immune system: active individuals show a different pattern of proinflammatory markers in the blood serum, with every exercise session generating an immune-stimulatory effect which changes the immunologic serum profile also at rest. Thus, regular exercise has an anti-inflammatory long-term effect.

Hypothesis and Objectives: With this project the investigators seek to demonstrate distinct immunologic changes, assessing cytokine serum profiles and changes in peripheral blood mononuclear cell (PBMC) characteristics upon a medically guided training regimen. The investigators assume that the antitumor immune response is positively affected by the training therapy regimen.

Setting and Methods. To exactly define "exercise" in this setting, as a first step the investigators will test two exercise types in healthy individuals. According to the individual exercise capacity as determined by spiroergometry, healthy subjects will either perform moderate-intensity continuous exercise (MICE), or a high-intensity interval training (HIIT). By means of venous blood sampling before and after training the investigators determine the respective changes of serum immune markers through exercise. The same two training types will then be performed by lung cancer patients upon immunotherapy, with one patient group doing MICE-sessions, one group doing the HIIT and a third group who will receive general exercise recommendations but otherwise will not undergo supervised training. Inflammatory serum parameters and PBMC characteristics will be compared between the groups. Moreover, the overall aerobic capacity (and respective changes before and after the training intervention), as well as quality of life will be analysed.

Patients in the exercise groups will be advised to train once a week under medical supervision, and to walk briskly for 30 minutes every day of the week in addition. The investigators' hypothesis is, that exercise should be implemented as a complementary treatment strategy in the lung cancer treatment setting, possibly improving not only physical health and wellbeing but also treatment response. In addition to improving the patients' quality of life by a better physical capacity and fitness, helping the participants in everyday activities, the investigators propose that the implementation of exercise programs in various oncologic settings in future may improve the patients' outcome.

Scientific Novelty. Standardization of exercise regimens in oncologic scenarios in the existing literature is generally poor. The investigators carry out one of the few studies where the type, duration, timing and intensity of exercise in both exercise groups is clearly defined according to the F.I.T.T. (frequency, intensity, type, time)-principle, comparing two different training modalities to sedentary control patients, respectively. Exercise needs to be seen as a drug, and like in any drug the optimum dose must be clearly outlined.

• Cytokine analysis from peripheral blood sampling [Срок оценки: From enrollment to after the 12 week intervention, i.e. a period between 12-14 weeks]
• Number of participants with changes in mitochondrial function (Seahorse analysis) [Срок оценки: From enrollment to after completion of the exercise intervention, i.e. a period between 12-14 weeks]
• Mass spectrometry - Lipidomics [Срок оценки: From enrollment to after completion of the 12 week exercise intervention, i.e. a time period between 12 and 14 weeks]
• Aerobic capacity [Срок оценки: From enrollment to after completion of the 12 week training therapy intervention, i.e. a time period between 12 and 14 weeks]
• Quality of life - EORTC-QLQ C30 (German version) [Срок оценки: From enrollment to after completion of the 12 week training therapy intervention, i.e. a period between 12 and 14 weeks]
• Quality of life - FACT-L scale (German version) [Срок оценки: From enrollment to after 12 weeks, i.e. a period between 12 and 14 weeks]
• Bodycomposition / Bioimpedance measurement [Срок оценки: Enrollment to after 12 weeks, i.e. a period between 12 and 14 weeks]