Identification of Changes in Cancer-related Fatigue and Physical Activity and Their Association in Patients With Inoperable Lung Cancer: a Longitudinal Observational Study

Cancer-related fatigue (CRF) will be measured using the FACIT-F and EMA. The Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) is a 13-item questionnaire with each item answered on a 5-point rating scale, which has been validated and frequently used in cancer populations. The questionnaire is based on a 7-day recall period. Scores range between 0 and 52, where higher scores represent lower fatigue levels. The minimum important difference for the FACIT-F is between 3 to 4 points.

Regarding EMA, patients will install the m-path application on their smartphone. Patients will be asked to fill in 3 prompts per day for 15 (M1 and M2) or 8 (M3 and M4) consecutive days, answering questions about fatigue ("I feel fatigued right now" from 1 (not at all) to 7 (very)). The 3 prompts will be sent at a random time within 3 blocks per day (between 8h and 10h, between 12h and 14h, and between 18h and 20h). Prompts will be available for 30 minutes and a reminder will be sent after 15 minutes. Daily symptom rating will be calculated by taking the average of the 3 prompts and will be used for further analyses.

Physical activity (PA) will be measured during one or two week(s) (depending on the treatment phase) using an Actigraph GT3X and Dynaport Movemonitor+, both validated accelerometers. Following recommendations on wear location, participants will be asked to wear the devices at the waist (on the same belt) during daytime and switch the Actigraph GT3X to the non-dominant wrist during the night (to measure sleep duration). Valid PA data is considered when a patient has at least 8 hours wear time during waking hours. The average daily step count (based on Dynaport Movemonitor+) and minutes of MVPA (based on Actigraph GTX3) per day of all valid days are the PA outcomes.

Symptoms of dyspnea occurring during daily life activities will be assessed through the Chronic Respiratory Disease Questionnaire Self-Administered Standardized (CRQ-SAS).

The European organization for the Research and Treatment of Cancer Questionnaire (EORTC QLQ-C30) is a clinically valid and useful tool for assessing quality of life in lung cancer patients.

The European organization for the Research and Treatment of Cancer Questionnaire - lung cancer module (EORTC QLQ-LC13) is a clinically valid and useful tool for assessing quality of life, specifically for lung cancer patients.

The Depression Anxiety Stress Scales-21 (DASS-21) has been developed as a single screening tool to measure comorbid depression, anxiety, and stress disorders in healthy individuals and represent a psychometrically viable option for health systems and clinicians when assessing distress in cancer patients.

The Pittsburgh Sleep Quality Index (PSQI) is a valid and reliable tool to assess sleep quality across diverse populations. Total scores range from 0 - 20, with a score of 5 or more indicating a poor sleep quality.

A hand-held dynamometer (Microfet, Biometrics, NL) will be used to assess right isometric quadriceps strength. Patients will be tested while sitting in an upright position. The make test, as described by the ERS/ATS guidelines, will be performed. The best of at least three reproducible measurements (<10% variability) will be used for analyses.

Functional exercise capacity will be measured by a 1-min sit-to-stand (1MSTS) test and is a reliable and valid test for measuring functional exercise capacity in COPD patients. Each participant will perform the test twice, with the highest value used for subsequent analyses. Before and after the test, dyspnoea and fatigue will be monitored using the BORG-scale. The heart rate and SpO2 will be monitored continuously throughout the test.

Frailty will be assessed according to the criteria of Fried et al. The frailty phenotype is identified by the presence of three or more of the following components. Unintentional weight loss, exhaustion, low activity, slowness and weakness. Cut-off values for slowness and weakness were defined according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) recommendations.

Patients will be asked to wear a wearable (Garmin Vivosmart 5) throughout the whole study period as a measure of total volume of PA. Whereas wearables will not provide a valid outcome to be used as primary outcome, the data are valid to provide an overall measure of physical activity.

The DMOs, more specifically, gait pace, gait rhythm and gait bout-to-bout variability will be measured using the Dynaport Movemonitor +. This outcome measure is part of the PA measurement and therefore requires no additional measurement.

Sleep time will be measured using the Actigraph GT3X, worn on the non-dominant wrist during the night.

The occurrence of (re)hospitalization, all-cause mortality and cancer-related mortality in the year after the start of the study will be reported.