Pain, Body Composition and Physical Activity in Childhood Cancer.
Condition: Childhood Cancer
Study type: Observational

Summary: 
      Comparing baseline assessments of children with cancer and their parents with baseline
      assessments of healthy children and their parents in a case-control study will allow the
      investigators to make the comparison in terms of pressure hyperalgesia, pain catastrophizing,
      energy-balance related behavior, attention control and attention bias between healthy
      children and cancer patients. This also enables the investigators to compare parents of
      healthy children with parents of cancer patients in the field of catastrophizing about the
      pain of their child and responses to child's pain experiences. Correlations can also be
      calculated between, for example, pain pressure thresholds and energy-balance related
      behavior.
    

Detailed description: 
      Participant recruitment

      Cancer patients will be recruited by the oncology department of the children's hospital of
      the University Hospital Brussels and Ghent. All children with cancer between 8-18y and their
      parents will be informed about the study and receive a consent form. The recruitment
      procedure will start in July 2019 and pursue until the calculated sample size is reached.
      Healthy controls will be recruited from several schools in the neighborhood and from family
      and acquaintances of the hospital personnel and researchers. In order to be able to compare
      their outcomes with the intervention group, they will be selected based on age and sex.
      Cancer patients with a portal catheter will also be included in a concurrent pilot randomized
      controlled trial, including the same baseline assessments. In this pilot randomized
      controlled trial, children will be distracted by a humanoid robot during painful medical
      procedures. Given the observation that children up to 12 years of age are more likely than
      children over 12 years to believe that a robot possesses human characteristics, only the
      children between the ages of 8 and 12 years also participate in this randomized controlled
      trial. The lower age limit is chosen because child self-report questionnaires have been
      validated from that age. Self-reports in children also require a variety of cognitive skills,
      which develop gradually and are only acquired at the age of 7 or 8 in most children. Children
      and their parents can only be included in the study if they meet the inclusion criteria and
      after written informed consent from the (co-participating) parent/guardian and child is
      obtained. All parents/guardians and children will receive verbal and written information on
      all aspects of the study prior to consent for participation.

      Sample size calculation was performed with G*Power 3.1.9.2 (Franz Faul, Kiel, Germany). The a
      priori sample size calculation for this study was based on the sample size calculation of a
      previous study on pain hypersensitivity in juvenile idiopathic arthritis compared with
      healthy children. Targeting a study power of 80% with an α error probability of 0.05 and
      allocation ratio (N1/N2) defined as 1, the calculation revealed sample sizes of 26
      participants for the cancer group and 26 participants for the healthy controls (total sample
      size n=52). Accounting for a 10% dropout and keeping in mind that every sample size
      calculation has its limitations, the investigators propose studying at least 30 participants
      per group. Hence, the total number of participants to be included will be equal to 60.
      Because of the low number of new cases of childhood cancer (<15 years of age) per year in
      Belgium, the monocentric nature of this trial and the limited time for data collection (1
      year 9 months) the calculated sample size remains as a target.

      Risk management: In case of slow patient recruitment or a dropout rate that exceeds 10%, the
      age range of the participants will be extended (1) and French speaking children and their
      parents will no longer be excluded (2).

      Assessments

      Using an online questionnaire battery (↑ study feasibility), a number of measures will be
      assessed in the participating children and their parent(s). Online questionnaires will set up
      with Lime Survey.

      Demographics and medical data:

      Demographics (e.g. age, sex, ethnicity, socioeconomic status) and medical information will be
      collected from the patient's clinical charts and will be further supplemented by child and
      parent report.

      Anthropometrics:

      Basic anthropometrics (body height, body weight, waist circumference) will be gathered from
      each participating child. In addition, the body composition (i.e., body mass index, fat mass,
      fat free mass, muscle mass, intra- and extra cellular water, etcetera) will be determined by
      1 body composition analyzer (and an additioinial one in the healthy control group).

      Pressure hyperalgesia: pressure pain threshold (PPT) - CHILD:

      Pressure hyperalgesia of all participating children will be assessed by evaluating pressure
      pain thresholds (PPTs) at the dominant tibialis anterior and trapezius muscle by means of a
      digital pressure algometer (FPX 50, Wagner Instruments, Greenwich, CT, USA). To familiarize
      the subject with PPT measurements, one familiarization session will be done at the dominant
      upper leg. This technique to evaluate PPTs is a well-known and well validated method in the
      exploration of pathophysiological mechanisms involved in pain. High reliability levels of
      this technique are apparent from various studies. Also, pressure algometry has proven to have
      an excellent intra-rater agreement, a satisfactory inter-rater agreement and is well
      tolerated even by very young children.

      Pain catastrophizing Scale for Children (PCS-C) - CHILD:

      Children's catastrophic thinking about pain will be assessed with the Dutch version of the
      Pain Catastrophizing Scale for Children (PCS-C). The PCS-C consists of 13 items describing
      thoughts and feelings which the child may experience when they are in pain, in independent
      but strongly related dimensions of rumination, magnification and helplessness. Children are
      asked to rate how frequently they experience these thoughts and feelings on a 5-point Likert
      scale (0 = 'not at all', 4 = 'extremely'). The PCS-C results in a total score (ranging from 0
      to 52). The PCS-C has been shown to be a reliable and valid tool for children of 9 to 15
      years old and a strong internal consistency for pain catastrophizing (α=.90) is already
      demonstrated in the pediatric population.

      Attentional Control Scale for Children (ACS-C) - CHILD:

      Attention control will be assessed using the Attentional Control Scale for Children (ACS-C),
      which is a 20 item self-rating scale that assesses abilities to focus and shift attention.
      Ten statements assess the focusing component of attention (''When I concentrate myself, I do
      not notice what is happening in the room around me'') and the other ten statements assess the
      shifting of attentional resources (''When I am doing something, I can easily stop and switch
      to some other task''). A higher score on this scale indicates a better capacity of
      attentional control. Several studies report good internal consistency of the ACS-C.

      Attention Bias Assessment (dot-probe task) - CHILD:

      All participating children will be asked to complete a dot-probe task, which is a
      well-investigated reaction time task designed to measure selective attention to threat. In
      this dot-probe task, a threatening (i.e., pain) and neutral stimulus are presented
      simultaneously (i.e., a painful child face paired with a neutral child face) at two different
      spatial locations on a screen for a short time. Because both stimuli are in different spatial
      locations, they compete for attention. After the appearance of these stimuli, a dot probe
      emerges at the location of the threatening/pain stimulus (congruent presentation) or at the
      location of the neutral stimulus (incongruent presentation). The assignment of attention is
      measured by the time needed to respond to the dot probe. It is reasoned that responding to
      the probe will be faster when the child's attention is already allocated to location where
      the probe appears. Most probe detection studies found indeed that anxious individuals respond
      faster to congruent trials than to incongruent trials (congruency effect). This task is
      implicit, does not require instruction, and subjects need no or minimal training to perform
      the test successfully.

      Energy balance-related behavior (ENERGY Cross Sectional Survey (CSS) child) - CHILD:

      A selection of questions regarding physical activity and sedentary behavior of the ENERGY
      Cross-Sectional Survey (ENERGY CSS child) used in the ENERGY-project will be assessed by the
      participating children. This ENERGY-child questionnaire was developed in order to assess
      energy balance-related behaviors of the child as well as personal, family and
      school-environmental determinants related to these behaviors. The questionnaire has been
      shown to have good test-retest reliability and moderate to good construct validity for the
      large majority of items.

      Pain Catastrophizing Scale for Parents (PCS-P) - PARENT:

      Parent's catastrophic thinking about their child's pain will be assessed with the Dutch
      version of the Pain Catastrophizing Scale for Parents (PCS-P). The PCS-P consists of 13 items
      describing different thoughts and feelings that parents may experience in relation to their
      child's pain, in independent but strongly related dimensions of rumination, magnification and
      helplessness. Parents are asked to rate how frequently they experience these thoughts and
      feelings on a 5-point Likert scale (0 = 'not at all', 4 = 'extremely'). The developers
      reported strong internal consistency (α=.93) and validity as demonstrated by associations
      with parent distress and child disability.

      Inventory of parent/caregiver responses to the children's pain experience (IRPEDNA) - PARENT:

      To measure the responses of the parent to their child's pain episodes at T0, a shortened of
      the inventory of parent/caregiver responses to the children's pain experience (IRPEDNA) will
      be used. The scale is a self-administered questionnaire with three subscales: (1)
      solicitousness, (2) discouragement, and (3) promotion of well-behaviors and coping. The
      shortened version of 10 items only includes solicitousness and promotion of well-behaviors.
      All items reflect actions and behaviors that the parents may enact after seeing the
      children's pain behaviors. A good internal consistency of the 3 subscales has been
      demonstrated (coefficient alphas of 0.87, 0.83 and 0.87 respectively) and the subscales also
      show good criterion-related validity.
    

Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Probability Sample
Study population: 
        Cancer patients will be recruited by the oncology department of the children's hospital of
        the University Hospital Brussels and Ghent. All eligibel children between 8-18y and their
        parents will be informed about the study and receive a consent form. Healthy controls will
        be recruited from several schools in the neighborhood and from family and acquaintances of
        the hospital personnel and researchers. In order to be able to compare their outcomes with
        the intervention group, they will be selected based on age and sex.
      
Keywords: children; cancer; pressure pain threshold; energy-balance related behavior; pain catastrophizing; body composition