Cognitive Functioning and Health Related Quality of Life in Retinoblastoma Survivors

NCT06227962 | Enrolling By Invitation DMC

• 3 other identifiers: NL82126.029.22SKOCA 2009020Uitzicht 2021-13-Moll
• Study Type: observational
• Target: 240
• Locations: 1 country
• Sites: 1

Brief Summary

A retrospective crosssectional observational study of the effects of oncological treatment and frequent general anesthesia on neuropsychological development, psychosocial functioning (in terms of anxiety, depression, peer relations, perceived cognitive functioning and potential trauma) and health related quality of life in children and young adults who were treated or screened for retinoblastoma.

Conditions

Retinoblastoma; Neurocognitive Dysfunction; Health-Related Behavior

Keywords

Retinoblastoma; Cognition; Psychosocial functioning; HRQoL

Outcome Measures

Primary Outcomes (15)

• Estimated intellectual functioning (Neurocognition)

  Is assessed using 2 or 4 subtasks of the Dutch translation of the Wechsler Intelligence Scale for Children-Fifth edition (WISC-V-NL \[8-16 years\]) or the Wechsler Adult Intelligence Scale-Fourth Edition (WAIS-IV-NL \[16-35 years\]), depending on the visual ability of the participant. The 'Verbal Comprehension Index' (VCI) is assessed in all participants using the verbal subtests 'Similarities' and 'Vocabulary'. The 'Perceptual Reasoning Index' (PRI) is assessed in all sighted participants using the subtests 'Matrix Reasoning' and 'Block Design'. Index scores are calculated (range 55-145; M=100, SD=10) and outcomes between 90-110 are considered average, \<89 below average to borderline and \>110 above average to highly gifted. Subscale outcomes (range 0-20; M=10, SD=2) between 8-12 are considered average, \<8 below average, and \>12 above average.

  This concerns a cross-sectional study meaning that a neuropsychological assessment is carried out only once on all participants during the course of the study until study completion, approximately in 2027.

• Processing speed (Neurocognition)

  Vienna S2 'Auditory Reaction Time' is only assessed in all participants. Additionally, Vienna S1 'Visual Reaction Time' and S3 'Combined \[visual-auditory\] Reaction Time', and subtasks 'Digital Symbol Coding' and 'Symbol Search' of the WISC-V-NL or WAIS-IV-NL will be assessed in sighted participants as well. Outcomes of the VTS will be calculated in T-Scores (range 20-80; M=50, SD=10), where a T-score between 40 and 60 is considered average, \<40 below average and \>60 above average. A WISC-V-NL or WAIS-IV-NL Index score will be calculated (range 55-145; M=100, SD=10) and is considered average between 90-110, \<89 as below average to borderline, and \>110 as above average to highly gifted. Subscale outcomes (range 0-20) between 8-12 are considered average, \<8 below average and \>12 above average.

  This concerns a cross-sectional study and data will be collected until April 2027. The neuropsychological assessment is carried out only once on all participants during the course of the study until study completion.

• Memory (Neurocognition)

  In all participants, encoding and retrieval of verbal information will be assessed using the Rey- Auditory Verbal Learning Test (RAVLT). Working memory will be assessed using the subtests 'Digit Span' of the WISC-V-NL (8-16 years) or WAIS-IV-NL (17-35 years) resulting in the 'Working Memory Index' (WMI). RAVLT outcomes will be calculated in T-Scores (range 20-80), where a T-score between 40 and 60 is considered average, \<40 below average and \>60 above average. WISC-V-NL or WAIS-IV-NL Index scores will be calculated (range 55-145; M=100, SD=10) and outcomes between 90-110 are considered average, \<89 below average to borderline and \>110 above average to highly gifted. Subscale outcomes (range 0-20; M=10, SD=2) between 8-12 are considered average, \<8 below average, and \>12 above average.

  This concerns a cross-sectional study and data will be collected until April 2027. The neuropsychological assessment is carried out only once on all participants during the course of the study until study completion.

• Verbal fluency (Neurocognition)

  Verbal fluency will be assessed in all participants using the Semantic condition of the Dutch translation of the subtask Word Production of the Developmental Neuropsychological Assessment (NEPSY-III-NL \[age 8-12 years\]) or the Word Fluency Test (WFT \[13-35 years\]), a Dutch translation of the Controlled Oral Word Association Test (COWAT)). NEPSY-III-NL outcomes will be calculated in norm scores (range 0-20; M=10, SD=2), where outcomes between 8-12 are considered average, \<8 below average and \>12 above average. Outcomes of the WFT will be calculated in T-Scores (range 20-80; M=50, SD=10), were a T-score between 40 and 60 is considered average, \<40 below average, and \>60 above average.

  This concerns a cross-sectional study and data will be collected until April 2027. The neuropsychological assessment is carried out only once on all participants during the course of the study until study completion.

• Visual Motor Integration (Neurocognition)

  Visual Motor Integration will be assessed in sighted participants only, using the Visual-Motor Integration (VMI), Visual Perception (VP) and Motor Coordination (MC) of the Beery-Buktenica Developmental Test of Visual-Motor Integration, 6th Edition, Beery-VMI. Standard scores (range 48-155; Mean=100, SD=15) will be calculated, as well as T-scores (range 55-145; M=50, SD=10). Standard scores between 85-115 are considered average, \<85 below average to borderline, and \>115 above average to highly gifted. T-scores between 40 and 60 are considered average, \<40 below average, and \>60 above average.

  This concerns a cross-sectional study and data will be collected until April 2027. The neuropsychological assessment is carried out only once on all participants during the course of the study until study completion.

• Sustained Auditory Attention (Neurocognition)

  Sustained auditory attention will be assessed in all participants using the subtask Score! of the Test of Everyday Attention for Children (TEA-Ch \[6-16 years\]; Publication date 2004) or the Elevator task of the Test of Everyday Attention (TEA \[17-35 years\]; Publication date 1994). Regarding the TEA-Ch, norm scores (range 1-19; M=10, SD=2) will be calculated, whereas outcomes between 8-12 are considered average, \<8 below average, and \>12 above average. The Elevator task of the TEA has 7 subsets, the participants receives one point per correct subset (max=7). An outcome of 7 is considered 'Normal', 6 is considered 'Subclinical Abnormal', and \<5 is considered 'Clinical Abnormal'.

  This concerns a cross-sectional study and data will be collected until April 2027. The neuropsychological assessment is carried out only once on all participants during the course of the study until study completion.

• Executive functioning (Neurocognition)

  The Executive functioning (EF) tasks will be assessed in sighted participants only. The Stroop Color Word Test of the Delis-Kaplan Executive Function System (D-KEFS; Publication date 2007) measures selective visual attention, cognitive flexibility, inhibition and processing speed. The Trail Making Test (TMT) of the D-KEFS (publication data 2007) assesses attention, visual screening and cognitive flexibility. Scale scores will be calculated (range 0-20; M-10, SD=2) and scores between 8-12 are considered average, scores \<8 are considered below average, and scores \>12 above average.

  This concerns a cross-sectional study and data will be collected until April 2027. The neuropsychological assessment is carried out only once on all participants during the course of the study until study completion

• Anxiety (Psychosocial functioning)

  Anxiety (proxy 5-16 years and self-report 8-35 years) is assessed using a digital Patient Reported Outcomes Measurement Information System (PROMIS), computer adaptive testing (CAT) questionnaire (using the Dutch KLIK portal \[in Dutch Kwaliteit van Leven in Kaart/Mapping Quality of Life\]). A standard Total Scale score (range 0-100) of 0-59 indicate no anxiety symptoms, between 60-69 subclinical anxiety symptoms, and \>70 clinical anxiety symptoms.

  This concerns a cross-sectional study. Digital questionnaires will be assessed (if applicable) within two weeks of the neuropsychological assessment, only once on all participants during the course of the study until study completion (expected 2027).

• Depression

  Depression (proxy 5-16 years and self-report 8-35 years) is assessed using a digital PROMIS-CAT questionnaire (using the Dutch KLIK portal). A Standard Total Scale score (range 0-100) of 0-59 indicate no depression symptoms, between 60-69 subclinical depression symptoms, and \>70 clinical depression symptoms.

  This concerns a cross-sectional study. Digital questionnaires will be assessed (if applicable) within two weeks of the neuropsychological assessment, only once on all participants during the course of the study until study completion (expected 2027).

• Peer interaction (Psychosocial functioning))

  Peer interaction (self-report 9-17 years) is assessed using a digital PROMIS-CAT questionnaire (using the Dutch KLIK portal). A Standard Scale score (range 0-100) is calculated and outcomes. A norm score of \<29 is considered having poor peer relations, between 29 and 39 suboptimal peer relations, and \>39 having no peer relation problems.

  This concerns a cross-sectional study. Digital questionnaires will be assessed (if applicable) within two weeks of the neuropsychological assessment, only once on all participants during the course of the study until study completion (expected 2027).

• Perceived neurocognitive functioning (Psychosocial functioning)

  Perceived neuropsychological functioning (self-report 8-35 years) is assessed using a digital PROMIS-CAT questionnaire (using the Dutch KLIK portal). The questionnaire consists of 7 questions related to perceived problems regarding attention, focus, memory and reading comprehension. Questions are answered on a 4-point Likert scale (1=never, 2=sometimes, 3=often, 4=most of the time). Due to absence of standard data, standardized outcomes cannot be calculated. Outcomes of participants will be compared to each other, with a low score indicating good perceived cognitive functioning and a high score indicating declined perceived cognitive functioning

  This concerns a cross-sectional study. Digital questionnaires will be assessed (if applicable) within two weeks of the neuropsychological assessment, only once on all participants during the course of the study until study completion (expected 2027).

• Participation and Activity (Psychosocial functioning)

  Participation and activity (proxy 0-16 years and self-report 8-35 years) is assessed using the digital questionnaire Participation and Activity Inventory for Children and Youth (PAY-CY, publication date 2019, \[using the Dutch KLIK portal\]). Due to absence of standard data, outcomes (range 0-100) of participants will be compared to each other, with a high score indicating the absence of or fewer obstacles to activity and participation in daily life and a low score indicates much perceived obstacles. Outcomes relate to 'Activity and participation'. Additionally, 'Sensory functioning' and 'Parental component' is also assessed in the proxy questionnaires.

  This concerns a cross-sectional study. Digital questionnaires will be assessed (if applicable) within two weeks of the neuropsychological assessment, only once on all participants during the course of the study until study completion (expected 2027).

• Trauma (psychosocial functioning)

  Post-traumatic stress disorder (PTSD; proxy 3-16 years/ self-report 8-35 years) is assessed using the Dutch translation of the Child and Adolescent Trauma Screener (KJTS, in Dutch: Kind en Jeugd Trauma Screener \[3-18 years\]) or the PTSD Checklist for the DSM-5 (PCL-5 \[18-35 years\] using the Dutch KLIK portal)). Standard outcomes of the KJTS (range 0-60) regards 'Total Score', whereas \<15 is considered within normal limits, 15-19 subclinical development of PTSD and \>20 clinical development of PTSD. Regarding PCL-5, participants report a traumatic event ('Criteria A'). Standard outcomes are calculated in a 'Total Score' and sub scores corresponding to the DSM-5 criteria: 'Criteria B' (intrusive symptoms), 'Criteria C' (persistent avoidance), 'Criteria D' (negative alterations), and 'Criteria E' (arousal and reactivity). A Total Score (range 0-80) between 0-27 indicates no PTSD symptoms, between 28-32 subclinical PTSD development, and a total score of \>33 development of clinical PTSD.

  This concerns a cross-sectional study. Digital questionnaires will be assessed (if applicable) within two weeks of the neuropsychological assessment, only once on all participants during the course of the study until study completion (expected 2027).

• Health related quality of life (Psychosocial functioning)

  Health Related Quality of Life (HRQoL; proxy 0-16 years and self-report 8-35 years) is assessed using the digital questionnaires Preschool Children's Quality of Life questionnaire (TAPQOL \[0-2 years\]) or Pediatric Quality of Life Inventory (PedsQL \[3-35 years\] using the Dutch KLIK portal)). All outcomes (range 0-100) will be compared to Dutch norm reference data (bases on age and gender) and cut off scores differ among age. High scores indicate good functioning. A deviation of 10 points below the national average score of same-sex peers is clinically relevant. Subscales of the TAPQOL relates to 'Stomachache', 'Skin Problems', 'Respiratory Problems', 'Sleeping Problems', 'Apatite', 'Positive mood', 'Anxiety', 'Livelihood' and 'Problem behavior'. Subscales of the PedsQL relate to the domains 'Physical Functioning' , 'Emotional Functioning', 'Social Functioning' and 'School functioning'.

  This concerns a cross-sectional study. Digital questionnaires will be assessed (if applicable) within two weeks of the neuropsychological assessment, only once on all participants during the course of the study until study completion (expected 2027).

• Study specific outcomes

  Four questions were asked to all participants: 1. Satisfaction with physical appearance, measured on a scale of 0-10 where 0 indicates completely dissatisfied and 10 indicates very satisfied. 2. Whether the participant has been under anesthesia for conditions other than retinoblastoma and if so, how often. (open end) 3. Whether the participant has been diagnosed with a psychiatric (DSM-5) disorder. (open end) 4. An open end question whether the participant would like to add or mention anything the participant considers worth mentioning.

  This concerns a cross-sectional study. Digital questionnaires will be assessed (if applicable) within two weeks of the neuropsychological assessment, only once on all participants during the course of the study until study completion (expected 2027).

Secondary Outcomes (4)

• Parental anxiety

  This concerns a cross-sectional study. The digital questionnaires will be assessed only once on all parents of participants (age 0-12) during the course of the study until study completion, expected in 2027.

• Parental depression

  This concerns a cross-sectional study. The digital questionnaires will be assessed only once on all parents of participants (age 0-12) during the course of the study until study completion, expected in 2027.

• Parental symptoms of distress

  This concerns a cross-sectional study. The digital questionnaires will be assessed only once on all parents of participants (age 0-12) during the course of the study until study completion, expected in 2027.

• Parental trauma

  This concerns a cross-sectional study. The digital questionnaires will be assessed only once on all parents of participants (age 0-12) during the course of the study until study completion, expected in 2027.

Study Arms (3)

Retinoblastoma Survivors

Children and adults who survived retinoblastoma (8-35 years of age)

Diagnostic Test: Neuropsychological assesment; Diagnostic Test: Psychosocial functioning and quality of life (questionnaires)

Retinoblastoma Risk Carriers

Children and adults who (might) carry a genetic risk to develop retinoblastoma (8-35 years of age)

Diagnostic Test: Neuropsychological assesment; Diagnostic Test: Psychosocial functioning and quality of life (questionnaires)

Parents

Parents of Rb patients, Rb survivors, or Rb risk carriers (6 months-12 years of age)

Diagnostic Test: Parental psychosocial functioning (questionnaires)

Interventions

Parental psychosocial functioning (questionnaires) DIAGNOSTIC_TEST

Anxiety (PROMIS); Depression (PROMIS); Distress Thermometer-Parents (DT-P); Trauma (PCL-5)

Parents

Neuropsychological assesment DIAGNOSTIC_TEST

Estimated intelligence (subtasks of Wechsler Intelligence Scale for Children - Fifth edition -Dutch version \[WISC-V-NL\] or Wechsler Adult Intelligence Scale - Forth edition - Dutch version \[WAIS-IV-NL\]); Vienna reaction time; Rey auditory verbal learning test; Word fluency; Beery-Buktenica Developmental Test of Visual-Motor Integration, 6th Edition; Test of Everyday Attention for Children (TEA-Ch), subtask Score!/ or Test of Everyday Attention (TEA), subtask Elevator task; Trail making test; Word-color interference test

Retinoblastoma Risk Carriers; Retinoblastoma Survivors

Psychosocial functioning and quality of life (questionnaires) DIAGNOSTIC_TEST

Anxiety (PROMIS); Depression (PROMIS); Peer-interaction (PROMIS); Perceived neurocognitive functioning (PROMIS); Participation and activity (PAY-CY); Trauma (KJTS/PCL-5); Health related quality of life (PEDSQL)

Retinoblastoma Risk Carriers; Retinoblastoma Survivors

Eligibility Criteria

• Age: 6 Months - 35 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Approximately 350 Rb survivors and 310 Rb risk carriers (\<35 years) that have been treated or screened at the Dutch Retinoblastoma Expertise Center of the Amsterdam University Medical Center

You may qualify if:

• Rb diagnosis, (main) treatment and follow-up of Rb patients and -survivors, or Rb screening took place at the Dutch Retinoblastoma Expertise Center of the Amsterdam University Medical Center,
• Rb survivor or former Rb risk carriers is between 8 and 35 years old,
• Average understanding of the Dutch language.
• Being a caregiver of a Rb survivor or Rb risk carrier that have been diagnosed and receive(d) (main) treatment and follow-up or screening at the Dutch Retinoblastoma Expertise Center of the Amsterdam University Medical Center,
• The related Rb survivor or Rb risk carrier is \< 12 years old,
• Average understanding of the Dutch language.

You may not qualify if:

• Pre-existing documented developmental delay and/or severe cognitive impairments (IQ \<70),
• Having an active, uncontrolled psychiatric illness,

Sponsors & Collaborators

• Amsterdam University Medical Center: lead

Study Sites (1)

Amsterdam University Medical Center

Amsterdam, North Holland, 1081 HZ, Netherlands

Location

MeSH Terms

Conditions

Retinoblastoma; Cognition Disorders; Health Behavior

Condition Hierarchy (Ancestors)

Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue; Retinal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases, Hereditary; Eye Diseases; Retinal Diseases; Neurocognitive Disorders; Mental Disorders; Behavior

Study Officials

• Annette C. Moll, MD PhD

  Amsterdam University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., PhD, Clinical professor

Study Record Dates

• First Submitted: December 20, 2023
• First Posted: January 29, 2024
• Study Start: October 26, 2023
• Primary Completion (Estimated): October 30, 2026
• Study Completion (Estimated): March 31, 2028
• Last Updated: December 4, 2025

Record last verified: 2025-11

Locations

NL (1)