New Strategies to Detect Cancers in Carriers of Mutations in RB1
Condition: Retinoblastoma; Secondary Primary Malignancies After Retinoblastoma
MeSH terms: Neoplasms; Retinoblastoma
Study type: Observational

Summary: 
      Rationale: Individuals with a cancer predisposition due to a mutation in the paradigm tumor
      suppressor gene RB1, have a high risk to develop the childhood cancer retinoblastoma (Rb).
      Biopsies are not possible in Rb, before treatment selection. Heritable Rb patients have also
      a high risk to develop other types of second primary, either childhood or adult, malignancies
      (SPMs), notably sarcomas and melanomas. Remarkably, SPMs are now the leading cause of death
      in heritable-Rb-survivors. Unfortunately, there are no well-developed regular surveillance
      protocols for SPMs in Rb survivors available right now. Recently, new non-invasive cancer
      test have been developed, based on either RNA-sequencing data from platelets (ThromboSeq), or
      on extracellular membrane vesicles (EVs) derived from tumor cells present in blood.

      Objective:

        -  Determine the non-cancerous baseline in adult RB1-mutation carriers
           (heritable-Rb-survivors).

        -  Contribute to the biobanking of blood and cancerous tissues from RB1-mutation carriers
           with SPMs.

        -  The development of blood-based tests, either platelet or EV-based, for the detection of
           (the type of) tumors in RB1-mutation carriers.

      Study design: Cross-sectional multicenter trial.

      Study population:

        -  40 Rb patients (children),

        -  40 controls (children),

        -  153 Rb survivors (adults),

        -  153 controls (adults),

        -  10 Rb survivors with SPM (children/adults).

      Main study parameters/endpoints:

        -  Determine the non-cancerous baseline in adult RB1-mutation carriers
           (heritable-Rb-survivors).

        -  Contribute to the biobanking of blood and cancerous tissues from RB1-mutation carriers
           with SPMs.

      Nature and extent of the burden and risks associated with participation, benefit and group
      relatedness:

      Two blood samples totalling 10ml blood will be collected for every participant. Additionally,
      a short questionnaire has to be filled in concerning their and their family's cancer history.
      Blood draws will be done, when participants are already present in the hospital for other
      appointments, and thus no extra visits are required. For all children, blood will be
      collected through an already present IV, and so no extra venepuncture is required. Children
      have to be included because Rb is a tumor only present in this patient group.
    


Intervention name(s): blood draw
Intervention type(s): Other
Intervention description(s): Control samples for the Rb survivor group (adult) are already available at the VUMC for the platelet study; unselected volunteers from an anti-cancer campaign. Control samples (adult) for the EV study will be collected in a blooddrive at the Essen site.
Pediatric patients. For the pediatric Rb patients, blood draw is part of standard care (3mth-4y). The control blood samples of healthy children (12) will be drawn from healthy children, where the blood draw is already part of otherwise planned care (e.g. patients which are completely healthy besides having an unrelated problem for which surgery is required). Controls will be age-matched as much as possible.
Observational model: Case-Control
Time perspective: Cross-Sectional
Sampling method: Non-Probability Sample
Study population: 
        Control samples for the Rb survivor group (adult) are already available at the VUMC for the
        platelet study; unselected volunteers from an anti-cancer campaign. Control samples (adult)
        for the EV study will be collected in a blooddrive at the Essen site.

        Pediatric patients. For the pediatric Rb patients, blood draw is part of standard care
        (3mth-4y). The control blood samples of healthy children (12) will be drawn from healthy
        children, where the blood draw is already part of otherwise planned care (e.g. patients
        which are completely healthy besides having an unrelated problem for which surgery is
        required). Controls will be age-matched as much as possible.
      
Biospecimen description: 
      Serum, white blood cells, platelets, tissue
    
Keywords: Retinoblastoma; blood test; liquid biopsy; RB1; cancer; Secondary primary malignancies; SPM