Cognitive Functioning And Health Related Quality Of Life In Retinoblastoma Survivors: The Role Of Cancer Treatment And Repeated Anesthesia

Retinoblastoma (Rb) is the most common form of ocular cancer in children, with
high survival rates in developed countries (>90%). Rb can develop unilateral
(sometimes hereditary), or bilateral (always hereditary). Children are usually
diagnosed at a young age (< 5 years) and are subjected to an intensive
treatment and follow-up protocol immediately after. If Rb is diagnosed in early
disease stages, eye-saving treatment could be provided, such as laser, cryo-,
chemotherapy and/or radiotherapy -or a combination of these. When discovered in
a later disease stage, enucleation is often inevitable. Brothers and sisters or
offspring of heredity Rb survivors that are at risk to develop Rb themselves
(so called *Rb risk carriers*) will be screened according to the Dutch Rb
Screening Protocol. The medical treatment and follow-up of Rb patients and
screening of Rb risk carriers takes place under general anesthesia (GA) up to
four or five years of age. At this age the brain is still developing and
therefore extra vulnerable to iatrogenic damage, including neuropsychological
complications. Immediate effects of the oncological treatment, as well as
secondary effects due to multiple GA on cognitive development in Rb survivors
is still understudied. Rb survivors report disease-related limitations in daily
life and lower health related quality of life (HRQoL), which might be related
to impaired cognitive functioning. Apart from possible immediate or secondary
treatment effects, children with Rb are known to be experiencing psychosocial
struggles, including anxiety and depression, declined participation and/or
pediatric trauma, which may negatively affect HRQoL as well. Despite the impact
on general wellbeing and HRQoL, the cognitive and emotional aspects of Rb are
largely under addressed in pediatric care. It is important to gain insight in
the cognitive development and psychosocial functioning from childhood into
young adulthood of Rb survivors, as well psychosocial functioning of the
parents in order to provide timely interventions, minimizing possible long-term
consequences. It is hypothesized that extensive treatment and multiple GA is
negatively associated with cognitive functioning, psychosocial functioning and
HRQoL in Rb survivors and Rb risk carriers. Moreover, that psychological
struggles and/or trauma strengthen these associations.

The specific aim of the current study is to investigate the impact of
oncological treatment and multiple GA in Rb survivors and Rb risk carriers
(8-35 years) on cognitive functioning, psychosocial functioning and HRQoL.
Furthermore, psychological struggles of parents in terms of anxiety,
depression, parental distress and parental trauma of parents of young Rb
patients/survivors, and risk carriers (0-12 years), will be also taken into
account.

A cross-sectional observational cohort study will be conducted with three core
outcomes:
1. Cognitive functioning of Rb survivors and former Rb risk carriers (8-35
years old); using comprehensive and neuropsychological testing addressing
estimated intelligence, tempo and processing speed, memory, language, visual
motor integration, attention and executive functioning.
2. Psychosocial functioning of Rb survivors and former Rb risk carriers (8-35
years old); using online questionnaires addressing anxiety, depression,
adaptive functioning and activity and pediatric trauma.
3. Psychosocial functioning of parents (child 0-12 years old); using online
questionnaires addressing anxiety, depression, parental distress and parental
trauma.

Nationwide norm data will be used for both neuropsychological- as well as
questionnaire outcomes to assess clinical significance. Outcomes of Rb
patients/survivors and (former) Rb risk carriers will be compared to each other
as well.
Within the Rb survivors cohort different treatment groups will be discerned and
compared to each other: such as only enucleation (EN), versus only focal
therapy (FT), versus only selective intra-arterial chemotherapy (SIAC), versus
only radiotherapy (RT), versus combinations of those treatments, including
systemic chemotherapy.

The neuropsychological assessment regards one appointment and will be assessed
in combination with a regular out-patient visit to the ophthalmology
department, or at the survivors* or Rb risk carrier*s own home. Digital
questionnaires are completed at the participants home in their own time on
their personal computer. Physical or psychological discomfort is expected to be
low to moderate and aftercare is provided when necessary. Presentation of
retinoblastoma only occurs during childhood and therefore it is important to
now the (late) effects of treatment and follow-up on development during
childhood and adolescence. Furthermore, problems regarding cognitive
functioning, psychological functioning and HRQoL can differ with age.