Fit to Fight Childhood Cancer

Cancer-related fatigue measured by the Pediatric Quality of Life Inventory (PedsQL) 3.0 Multidimensional Fatigue Scale. The PedsQL Multidimensional Fatigue Scale is composed of 18 items comprising three dimensions. Scores are transformed on a scale from 0 to 100. Higher scores indicate lower fatigue.

Stress reactivity measured by the Mainz Resilience Score for childhood cancer (MRScc). The MRScc consists of 4 dimensions on mental health problems and 6 dimensions on stressor exposure. For both categories mental health problems and stressor exposure 4 - 400 points can be achieved. To calculate the resilience score, the category mental health problems is divided by the category stressor exposure. A score >0 means low resilience, a score < 0 means high resilience.

Resilience will be evaluated using the Brief Resilience Scale (BRS). BRS is a 6 item scale, the items are rated from 1 to 5. A total score is calculated by determining the sum of the individual items which result in a total score ranging from 6 to 30. A higher score means a higher resilience.

Resilience will be evaluated using the Child & Youth Resilience Measure-Revised (CYRM-R).

The items within the measures can be directly summed to gain a total score of an individual's resilience. For the unmodified 5-point measure (with responses going from 1-5), the minimum score is 17 and the maximum score is 85. For the overall measure and subscales, higher scores indicate characteristics associated with resilience.

General self-efficacy will be evaluated using the General self-efficacy scale (GSE). The total score is calculated by finding the sum of the 10 items. For the GSE, the total score ranges between 10 and 40, with a higher score indicating more self-efficacy.

Physical self-efficacy will be evaluated using the Physical exercise self-efficacy scale (PESE). The total score is calculated by finding the sum of the 10 items. For the GSE, the total score ranges between 5 and 20, with a higher score indicating more self-efficacy.

Risk will be evaluated using the Pediatric Pain Screen Tool (PPST). The questionnaire consists of nine items intended to identify a patient's risk status (high, medium, or low) of poor pain-related outcome using established psychosocial prognostic factors. The PPST is adapted from the Keele STarT Back Screening Tool (SBST) and validated for the pediatric population from 8 to 18 years. The PPST contains two subscales: physical and psychosocial items. Summing all items, PPST total scores range from 0 to 9. Psychosocial subscale scores range from 0 to 5 and 0 to 4 for the physical subscale. The low risk group was defined as a PPST total score of 0 to 2 (PPST total cutoff for disability minus the PPST psychosocial subscale cutoff for psychosocial distress). For the high-risk group, a score of 3 or greater for the PPST psychosocial subscale was defined as high-risk, and last, a total PPST score greater than or equal to 3 and psychosocial subscale 0 to 2 were defined as medium risk.

The subjective pain rating will be measured using the Face Pain Scale - Revised (FPS-R), that is a self-report measure of the actual, subjective pain intensity developed for children. The FPS-R was adapted from the Faces Pain Scale to make it possible to score the sensation of pain on the 0-to-10 metric in children and adolescents. The scale shows a close linear relationship with visual analog pain scales across the age range of 4-16 years and has already been used and validated with children and adolescents. In addition, a visual analog scale (0-10, VAS) is used to assess the current perception of pain in study participants aged 8 years and older.

In addition to the face pain scale - revised (FPS-R), a visual analog scale (0-10, VAS) is used to assess the current perception of pain in study participants aged 8 years and older.

Parent Fear of Pain will be measured using the Parent Fear of Pain Questionnaire (PFOPQ). The questionnaire intended to assess a parent's pain-related fears and avoidance behaviour. The total scale score reflects parents' own pain-related fear and avoidance in the context of their child's pain, and the four subscale scores reflect: Avoidance, Fear of Pain, Fear of School, and Fear of Movement. Higher scores indicate higher levels of fear. The PFOPQ will be used since Fear and avoidance have been consistently associated with poor pain-related outcomes in children.

Pain Vigilance and Awareness will be measured using the Pain Vigilance and Awareness Questionnaire - Child version (PVAQ-C) that consists of 14 items to assess multidimensional aspects of attention to pain sensations in children. Items are rated on a six-point scale, ranging from 0 (never) to 5 (always). Items are summed to create a total score. Attention to pain is thought to be a key mechanism influencing the experience and chronification of pain. Sustained attention to pain is thought to lead to poor outcomes in both adults and children with chronic pain.

Physical activity level will be evaluated using the Modifed Recent Physical Activity Questionnaire (mRPAQ).

The duration of listed physical activities were reported (recall time: over the past 7 days). Descriptive Statistics will be performed.

Physical activity level will be evaluated using Modified Youth Physical Activity Questionnaire (mYPAQ).

The duration of listed physical activities were reported (recall time: over the past 7 days). Descriptive Statistics will be performed.

Physical activity level will be evaluated using Modified Children's Physical Activity Questionnaire (mCPAQ).

The duration of listed physical activities were reported (recall time: over the past 7 days). Descriptive Statistics will be performed.

In a semi-structured interview on physical activity, qualitative data will be collected regarding activity behaviour, motivating factors and barriers to physical activity.

Current physical activity and sedentary behaviour will be objectively recorded using an accelerometer. This should be worn during the day for 7 days. Accelerometer readings with at least four valid readings (≥ 500 min/day) will be included in the analysis. The physical activity recorded by the accelerometer will be expressed in "activity counts" (counts per minute, cpm).

Cardiopulmonary Exercise Testing (CPET) will be performed during an endurance test to exhaustion to determine the peak oxygen uptake (VO2peak).

Measured via Six Minute Walk Test (6MWT). Functional capacity is evaluated by the walked distance.

Measured via assisted 6-minute cycling test (A6MCT). Endurance performance is evaluated by the cumulative revolutions after 6 minutes.

Motor function will be measured via the QUICK motor function test.

A goniometer is used to measure the range of motion (ROM) during ankle flexion and extension, as well as knee and hip flexion.

Hamstrings flexibility will be measured via the sit and reach test.

Functional strength will be evaluated using the sit to stand test.

Arm and leg strength will be evaluated using a handheld dynamometer.

Static balance will be determined with the static stand test. The test requires the test person to stand on one leg for one minute. The number of contacts with the ground is counted. The static stand test has shown to be valid and reliable with children and is feasible with childhood cancer populations.

To assess functionality in every day life the Berg Balance Scale will be used. The scale consists of 14 items that can be rated with 0 to 4 points, with 0 rating a strong impairment. A maximum of 56 points can be reached.

A multifrequency (5, 50, 100 kHz) bioelectrical impedance analysis is performed using a phase-sensitive impedance analyser (BIAcorpus RX4004M). For this purpose, a sinusoidal alternating current with a constant intensity is applied to the patient's wrists and ankles. The phase angle (PA, ° degree) is measured by the impedance analyser as the phase shift between current and voltage. The phase angle provides conclusions about nutritional status and body composition.

WHO (Five) Well-Being Index (1998 version) is used to measure Mental Health.The WHO-5 consists of five statements, which respondents rate according to the scale below:

All of the time = 5 Most of the time = 4 More than half of the time = 3 Less than half of the time = 2 Some of the time = 1 At no time = 0. The total raw score, ranging from 0 to 25, is multiplied by 4 to give the final score, with 0 representing the worst imaginable well-being and 100 representing the best imaginable well-being.

Warwick-Edinburgh Mental Well-being Scale (WEMWBS) is used to measure Mental Health. WEMWBS is a 14 item scale of mental well-being covering subjective well-being and psychological functioning, in which all items are worded positively and address aspects of positive mental health. The total score of the 14-item scale WEMWBS is obtained by summing the score for each of the 14 items. The scoring range for each item is from 1 - 5 and the total score is from 14-70.

Health-Related Quality of Life measured by the Measurement Model for the Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales questionnaire.

On the PedsQL Generic Core Scales, for ease of interpretability, items are reversed scored and linearly transformed to a 0-100 scale, so that higher scores indicate better HRQOL (Health-Related Quality of Life).

Health-Related Quality of Life measured by the Measurement Model for the Pediatric Quality of Life Inventory (PedsQL) 3.0 Cancer Module questionnaire.

Scores are transformed to a 0 to 100 scale. Higher scores indicate lower problems.

The subject's gait pattern is evaluated using a video- and sensor-based gait analysis system. The following variables will be recorded: velocity, cadence, step length, step width, single and double support and stance.

To assess patients functionality in everyday life the Gillette Functional Assessment Questionnaire - Walking Scale (FAQ) is used. The FAQ is a parent- or self-report walking scale on the patients' general ability to function in their social environment and consists of 10 items. A rating of 6 or lower indicates restricted walking abilities. A score of 10 points is considered as typical/normal.

To assess patients functionality in everyday life the Functional Gait Index (FGI) is used.

The FGI evaluates the dynamic balance while walking. The Index consists of 10 items. Each item can be rated with a score from 0 to 3, with 0 equaling a strong impairment. No impairment in functional gait can be observed if a patient reaches the maximum of 30 points.

To assess patients functionality in everyday life the Timed-up-and-go test (TUG) will be performed.

The TUG refers to the capacity of children and adolescents to do daily activities. The TUG measures the time in seconds required to rise from a sitting position in a standard chair, walk 3m, turn, walk back to the chair and sit down.

List of relevant comorbidities assessed by medical questionnaire and medical records. Descriptive Statistics will be performed.

Socioeconomic status will be assessed in order to perform a confounder analysis for the main outcome cancer-related fatigue.

The calculation of the socioeconomic status index is based on the dimensions "levels of education", "occupational status" and "income". Scores for each dimension ranged from 1 to a maximum of 7. Since the 3 subscales are included in the calculation with the same weight, the socioeconomic status index can assume values between 3.0 and 21.0. Higher scores mean higher socioeconomic status.