Randomized Controlled Trial of the Effects of Combined Resistance and AerobiC Exercise on Health-related Quality of Life in Patients Undergoing First-line Chemotherapy for Metastatic Colorectal Cancer (REACH)

The difference in means of the average global health-related quality of life score in intervention versus control, regardless of intervention compliance; disease progression; cancer treatment discontinuation or dose-modifications; changes in initially scheduled cancer treatment; and engagement in alternative cancer care, in physical activity, structured exercise training, or municipality-based cancer rehabilitation. Health-related quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Scores range from 0 to 100, with higher scores indicating better health-related quality of life.

The difference in means of the average health-related quality of life score (global score and score for each subcomponent) in intervention versus control, regardless of intervention compliance; disease progression; cancer treatment discontinuation or dose-modifications; changes in initially scheduled cancer treatment; and engagement in alternative cancer care, in physical activity, structured exercise training, or municipality-based cancer rehabilitation. Health-related quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30. Scores range from 0 to 100.

The difference in means of the average colorectal cancer-specific symptoms inter-vention versus control, regardless of intervention compliance; disease pro-gression; cancer treatment discontinuation or dose-modifications; changes in initially scheduled cancer treatment; and engagement in alternative can-cer care, in physical activity, structured exercise training, or municipality-based cancer rehabilitation. Health-related quality of life will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire CR 29. Scores range from 0 to 100.

Between-group difference in changes in cancer related fatigue from randomization to 6, 12, 18, 36, 52, 104, and 156 weeks after randomization. Cancer related fatigue will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core FA12. Scores range from 0 to 100.

Patient-reported symptomatic adverse events will be assessed, using the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE). A total of 42 symptomatic adverse events have been preselected based on high expected prevalence in patients with colorectal cancer.

Serious adverse events.

Unscheduled hospitalizations.

A chemotherapy dose delay is a delay of the planned administation of chemotherapy.

A chemotherapy dose reduction is a decrease of the planned dose of chemotherapy.

Discontinuation of chemotherapy is a premature discontinuation of the planned chemotherapy.

Between-group difference in changes from randomization to 18 weeks after randomization. Maximal oxygen uptake (mL/kg/min) will be estimated from ratings of perceived exertion obtained during submaximal exercise.

Between-group difference in changes from randomization to 18 weeks after randomization. Maximal oxygen uptake (L/min) will be estimated from ratings of perceived exertion obtained during submaximal exercise.

Between-group difference in changes from randomization to 18 weeks after randomization. Handgrip strength (kg) of the dominant hand will be measured using a dynamometer

Between-group difference in changes from randomizationto 18 weeks after randomization. Standing balance will be assessed using side-by-side stands, semi-tandem stands, and tandem stands. The time until the participants move their feet or grasp for support will be measured. The test is terminated after 10 seconds. Balance will be scored in accordance with the standardized scoring guidelines of the Short Physical Performance Battery (SPPB).

Between-group difference in changes from randomization to 18 weeks after randomization. Habitual 4 m gait speed will be measured on a 4 m straight, flat walking course and scored in accordance with the standardized scoring guidelines of the Short Physical Performance Battery (SPPB).

Between-group difference in changes from randomizationto 18 weeks after randomization. Chair rising capacity will be assessed using a sit-to-stand test. The time taken to perform five stands will be measured and scored in accordance with the standardized scoring guidelines of the Short Physical Performance Battery (SPPB).

Between-group difference in changes from randomization to 18 weeks after randomization. The Short Physical Performance Battery (SPPB) total score will be calculatedin accordance with the standardized scoring guidelines of the SPPB.

Between-group difference in changes from randomization to 18 weeks after randomization. Whole-body lean mass (kg) will be measured using bioelectrical impedance analysis.

Between-group difference in changes from randomization to 18 weeks after randomization. Whole-body fat mass (kg) will be measured using bioelectrical impedance analysis.

Between-group difference in changes from randomizationto 18 weeks after randomization. Body mass (kg) will be measured using an electronic scale.

Between-group difference in changes from randomizationto 18 weeks after randomization.

Between-group difference in changes from randomization to 18 weeks after randomization. Reported as beats/min.

Between-group difference in changes from randomizationto 18 weeks after randomization. Reported as mmHg.

Between-group difference in changes from randomizationto 18 weeks after randomization. Reported as mmHg.

Overall survival, defined as the time from randomization to death.

5-year progression-free survival, defined as the time from randomization to disease progression or death.

Time to progression, defined as the time from randomization to disease progression

Time to treatment failure, defined as the time from initiation of treatment to early discontinuation.

Proportion of participants undergoing intended curative surgery.