비소세포폐암에서 면역요법 반응을 개선하기 위한 도구로서의 운동 (ImmuEX)

실험적: 지속적인 운동

이 그룹의 환자들은 주 2회 감독 하에 이루어지는 중강도 지속 운동(MICE)과 주 5회 30분간의 가정 기반 걷기 운동을 추가로 포함하는 12주간의 훈련 치료 요법을 받게 됩니다.

행동: 운동

12주 동안 각각 지속형 운동을 하는 1개 연구군과 고강도 인터벌 운동을 하는 1개 연구군을 비교합니다. 두 군 모두 비활동적인 대조군 환자와 비교됩니다.

다른 이름들:

• 홈베이스 걷기 운동

실험적: 고강도 간헐적 운동

이 그룹의 환자는 추가적으로 주 2회 감독 하 고강도 간격 운동과 주 5회 30분간 가정 기반 걷기 운동으로 구성된 12주간 훈련 치료 요법을 받게 됩니다.

행동: 운동

12주 동안 각각 지속형 운동을 하는 1개 연구군과 고강도 인터벌 운동을 하는 1개 연구군을 비교합니다. 두 군 모두 비활동적인 대조군 환자와 비교됩니다.

다른 이름들:

• 홈베이스 걷기 운동

활성 비교기: 컨트롤

이 그룹의 환자들은 활동적인 생활 방식에 관한 일반적인 권장 사항을 받지만, 감독 훈련 세션에 참여하지 않으며 가정 기반 운동도 하도록 요청받지 않습니다.

다른: 대조군

대조군 환자의 경우 일반적인 운동 권장사항(예: 모든 성인 개인에게 적합한 CDC 권장사항)이 제공되지만, 훈련 치료 중재는 수행되지 않으며 가정 기반 걷기 운동도 필요하지 않습니다.

FACS analysis of PBMCs

The FACS panel comprises:

CD4pos Helper T Cells, CD8pos Cytotoxic T Cells, Regulatory T Cells, Effector Memory T Cells, Naive/Memory Subsets, Activated/Exhausted T Cells, gamma-delta T Cells, Naive B Cells, Memory B Cells, Transitional B Cells, Classical Monocytes, Intermediate Monocytes, Non Classical Monocytes, NK CD16pos, NK CD16neg, Neutrophils, Basophils, Mast Cells, Viable vs. Dead Cells, Immune Checkpoint Subsets, Activation/Proliferation Markers.

The total numbers and percentages of cells positive for the above listed markers are the primary outcome measures.

The surface marker profile of PBMCs as a whole will define the outcome, showing differences between exercising and sedentary patients, e.g.: "In patients from the exercise group, XX% of naive B cells were found, and XX% of CD4pos Helper T Cells, and XX% CD8pos Cytotoxic T Cells were found. In patients from the control group, the proportion of naive B cells was XX...".

Cytokine analysis from peripheral blood sampling

IFN gamma, IL-13, GM-CSF, IL-1β, IL-5, sCD25 (IL-2Ra), IL-4, VEGF, IL-17A, IL-18, CCL4 (MIP-1β), IL-15, IL-12p70. The count of the above listed cytokines in pg/ml will be recorded in venous blood samples, with higher values after exercise indicating a more pronounced inflammatory response.

Blood plasma samples from the patients will be collected at the beginning and after the 12 weeks exercise intervention for cytokine testing. Additionally, cytokine profiling will be done before and after one exercise bout to illustrate acute changes. Multiplex detecton kits (Legendplex) will be used for cytokine profiling.

For every cytokine, differences will be recorded in one patient at enrollment and after completion of the 12 week training therapy. Differences between the exercising and non-exercising patients will be recorded as well. E.g. "IFNgamma levels were on average XX pg/ml before the intervention. After the intervention period of 12 weeks, IFNgamma levels were on average XX pg/ml."

Number of participants with changes in mitochondrial function (Seahorse analysis)

Mitochondrial function parameters are combined to assess how well mitochondria work in a given patient.

Oxygen Consumption Rate (OCR), Extracellular Acidification Rate (ECAR), Glycolytic Rate, Glycolytic Capacity, Basal Oxygen Consumption Rate, Maximal Respiration, and Spare Respiratory Rapacity are assessed by means of a Seahorse assay using a Seahorse XF Analyzer from Agilent, that measures the real-time metabolic activity of live cells by simultaneously assessing mitochondrial respiration and glycolysis. The number of patients with changes in oxygen consumption rate (OCR), which indicates mitochondrial respiration, and the extracellular acidification rate (ECAR), which is linked to glycolysis, is analysed. Aberrations in mitochondrial function as well as changes from before to after the intervention in % of patients / total number of patients is assessed.

Mass spectrometry - Lipidomics

Marker Name (or m/z value), Retention Time and Intensity/Abundance of a given metabolite will be analysed in plasma samples. Markers comprise H4CH, H4A1, H4A2, TPA1, HDA1, IDPL, H4PL, Glutamine, L5CH, H3CH, TPA2, HDA2, L5PL, HDCH, H3A2, TPCH, L5PN, L5AB, V1FC, H3FC, L5FC, SPC, IDTG, V5FC, Glutamic acid, H4FC, Alanine, HDPL, V2PL, Glucose, LDCH, L4CH, H3A1, L4FC, V2TG. Lipidomics is used to describe the complete lipid profile within the patients' immune cells. It is a subset of the "metabolome". As opposed to classic analysis of carbohydrate metabolism, lipids are more stable, allowing for an analysis of frozen PBMCs. Our hypothesis is that upon the exercise program, lipidomics of the immune cells significantly change, allowing for a more favorable antitumor immune response. Total counts of each above-listed metabolite in the blood will be determined, e.g. in milligrams per deciliter and for every metabolite, changes between exercising and sedentary patients are recorded.

Aerobic capacity

With spiroergometry testing at the beginning of the exercise program and after completion of the program at 12 weeks, the investigators will assess potential changes in the patients' aerobic capacity.

The normal range for womens' VO2max starts at 30 ml/kg/min and for men at 35 ml/kg/min with lower ranges expected in the usually elderly tumor patients. Improvements over the 12 week intervention period will be recorded.

Quality of life - EORTC-QLQ C30 (German version)

The patient's quality of life will be assessed by two questionnaires, one for quality of life in cancer patients in general and one questionnaire specifically for lung cancer.

The EORTC-QLQ C30 (German version) has a range from 0-100 with higher values representing a better quality of life. Minimal Important Difference (MID): A change of 5 to 10 points is generally considered clinically meaningful.

Differences of 10 points are often used to indicate clinical relevance.

Quality of life - FACT-L scale (German version)

The FACT-L (Functional Assessment of Cancer Therapy-Lung) questionnaire has a maximum possible total score of 0 to 136, which includes the 27-item FACT-G (general) and the 9-item Lung Cancer Subscale (LCS). Higher scores indicate better quality of life.

Bodycomposition / Bioimpedance measurement

Bioimpedance measurement will be used to determine body composition (and possible increments in muscle mass). The measures are given in % of total body mass. Higher values of muscle mass are generally considered better and indicate a good response to training, whist declines in muscle mass are often observed in inactive cancer patients.