Lung cancer is the leading cause of cancer death worldwide and associated with high disease burden, symptoms and poor health-related quality of life (HRQoL). Lung cancer is the most commonly diagnosed type of cancer in China (with rates rising due to the smoking incidence) and is the leading cause of cancer-related death. The burden is on patients, families, the healthcare system and society, and will continue to rise into the future. The full impact of this in China has not yet occurred. New strategies are urgently required to improve survivorship. This multi-site, assessor blinded, two-arm superiority randomized controlled trial, conducted at two hospitals in China, aims to test the effect of exercise rehabilitation, compared to usual care (no exercise rehabilitation) on HRQoL and outcomes including physical function in 150 patients treated for lung cancer. The primary hypothesis is that exercise rehabilitation will be superior to usual care, in improving HRQoL at 12-weeks (post program). Secondary aims include include measuring the effectiveness of exercise rehabilitation, compared to usual care on function, physical activity, symptoms, mood, sleep and program costs.

One hundred and fifty patients with stage I-IIIA non-small cell lung cancer (NSCLC) 4-12 weeks following completion of treatment (including surgery with or without adjuvant therapy) and life expectancy greater than 6 months will be recruited from the affiliated hospital of Nantong University and the first affiliated hospital of Nanjing Medical University. At recruitment participants provide written informed consent, complete baseline assessment and to ensure concealment of allocation participants will be randomly allocated off-site to one of two arms (1:1 ratio). The intervention programs start following randomization and will continue for 12 weeks duration. Trained physiotherapists will provide the intervention. Patients in both arms will receive usual medical, physiotherapy and nursing care according to usual protocols. This does not involve exercise rehabilitation or advice. Additionally patients in intervention group (exercise rehabilitation) will receive a multimodal program which includes a 90 minute program at the hospital gymnasium in a supervised environment a minimum of once but up to twice per week. Rehabilitation will include aerobic (brisk walking) and resistance training and 30 minutes of 8 style Tai Chi). Participants will be advised to walk on days of non-attendance - this will be individualized with the aim to have participants increase to 30 minutes walking per day. Assessments will be conducted at baseline and then by blinded assessors at 12 weeks and 6 months post-baseline. Survival will be followed-up and censored at 1 year. This important study brings together a strong collaborative research team spanning China and Australia, involving medical doctors, physiotherapists and academics. The topic is important, novel and will generate clinically meaningful research for an international audience, aiming to improve the survivorship quality of patients with lung cancer.

The gut microbiome is a source of potentially disease-modifying bioactive metabolites and has recently been suggested to contribute to the pathogenesis of a variety of disorders. Therefore, we will study the gut microbiota and metabolites of the participants in order to identify potential the biomarkers for the clinical outcomes. Fresh faecal samples will be collected from all individuals before group assignment and after the completion of the program. The written informed consent will be provided by the participants.

Specifically, faecal samples (500mg) will be collected from participants who are free from gastrointestinal conditions, with no antibiotic exposure in the 28 days prior to sample collection. 'Snap' frozen samples will be stored at -80°C until the time of DNA extractions, 16S rDNA sequencing, and mass spectrometry analysis of the faecal metabolites. The distribution of gut microbiota before and after exercise will be compared and analyzed to obtain the species of bacterial flora that changed significantly after exercise. Moreover, the gut metabolites that changed significantly before and after exercise will be used to explore the biomarkers for the curative effect of rehabilitation exercise, as well as their relationships with the differentially distributed gut microbiota.