SPT Screening in Irradiated Hereditary Retinoblastoma Survivors

Multicenter Implementation of MR Imaging Studies in Irradiated Hereditary Retinoblastoma Survivors for Assessment of the Value of Craniofacial MRI Screening for Early Detection of Second Craniofacial Primary Tumors and to Enhance Survival

Rationale: Hereditary retinoblastoma survivors have an increased risk to develop second primary tumors (SPT) at a later age (with the highest risk in their teens), especially when they have been irradiated for retinoblastoma. The investigators hypothesize that regular screening with magnetic resonance imaging (MRI) could lead to early detection of SPTs leading to improved survival.

Objective: To evaluate the potential benefit of craniofacial MRI screening for early detection subclinical secondary cancers in patients previously irradiated for hereditary retinoblastoma.

Study design: Prospective multicenter non-invasive screening study. The total study duration will be four years of screening plus five years of follow-up.

Study population: Irradiated hereditary retinoblastoma patients 8-18 years old Main study parameters/endpoints: To evaluate the ability of craniofacial MRI for early detection of SPTs, the investigators will determine the sensitivity and specificity of MRI at detecting SPTs in irradiated hereditary retinoblastoma patients.

Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Included patients will undergo yearly craniofacial MRI for a period of 4 years. They will also be asked to fill out a psychological burden assessment form each visit. A potential risk of screening might be associated anticipatory anxiety, but screening also could be reassuring for patients and their parents; the investigators are not sure which will outweigh. False-positive results from MRI screening could lead to unnecessary further diagnostics leading to possible added anxiety and diagnostics (e.g., biopsies). However, this group of patients have a high risk of developing SPTs, with poor 5-year survival statistics. Early detection and therefore treatment of earlier stage (smaller) tumors, might therefore increase survival of this patient group.

Study Overview

• Status: Recruiting
• Conditions: Retinoblastoma
• Intervention / Treatment: Device: Magnetic resonance imaging

• Study Type: Observational
• Enrollment (Anticipated): 400

Contacts and Locations

• Study Contact: Name: Marcus C de Jong, MD, MSc; Phone Number: +31204440814; Email: mc.dejong@vumc.nl

Study Locations

• Netherlands
  • Noord-Holland
    • Amsterdam, Noord-Holland, Netherlands, 1081 HV
      • Recruiting
      • VU University Medical Center
      • Contact: Marcus C de Jong, MC, MSc; Phone Number: +31204440814; Email: mc.dejong@vumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

The potential study population will be irradiated hereditary retinoblastoma survivors in the Netherlands and joining centers from other countries. Currently, there is no screening program for these high-risk patients. The age of patients at highest risk of developing craniofacial SPTs is 8-18 years.

Description

Inclusion Criteria:

• Patients with a history of hereditary retinoblastoma
• Patients that have been treated with external beam radiotherapy for retinoblastoma
• Age of patients at the first MR scan: 8 years or older (≥8 years old), but only as soon as the MR scan can be performed without sedation or general anesthesia, and until and including 18 years of age (≤18 years old).

Exclusion Criteria:

• MRI related exclusion criteria:

  • Claustrophobia
  • Foreign non MR compatible metal objects in the body
  • Foreign incompatible metal objects in or close to the head
  • Exclusion criterium for additional contrast sequences: Allergic reaction to contrast administration in the past

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diagnostic accuracy of MRI for the detection of second primary tumors in hereditary irradiated retinoblastoma	The primary objective of the study is to evaluate the benefit of early detection of craniofacial second primary tumors with MRI in previously irradiated hereditary retinoblastoma survivors. The main outcome measure for assessing the benefit of screening will be the diagnostic accuracy of MRI for detecting craniofacial SPTs: sensitivity (true-positive and false-negative results) and specificity (true-negative and false-positive results).	4 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
5-year survival	A secondary objective is to assess the 5-year survival of second primary tumors (SPT) found by screening, SPTs missed by screening, and the non-SPT patients	9 years
Descriptive statistics	Recording and monitoring location and characteristics (clinical, radiological, histological, treatment) of patients with SPTs: total number of patients included, median follow-up time + range, number of asymptomatic SPTs detected by screening, number of symptomatic SPTs missed by screening, number of SPTs developed after the end of screening, number of SPTs that were totally resected, location of tumor, type of tumor, size of tumor	4 years
Feasability assessment	Assessment of the feasibility of such this screening program: (a) percentage of patients (or family) willing to participate; (b) compliance of patients and their families to the screening program	4 years
Assessing the psychosocial burden or benefit	Once a year during the visits, the patient will be asked to fill out the Hospital Anxiety and Depression Scale (HADS).	4 years

Collaborators and Investigators

• Sponsor: Amsterdam UMC, location VUmc
• Collaborators: ODAS
• Investigators: Study Chair: Jonas A Castelijns, PhD, Amsterdam UMC, location VUmc

Study record dates

Study Major Dates

• Study Start: October 1, 2014
• Primary Completion (Anticipated): October 1, 2018
• Study Completion (Anticipated): October 1, 2023

Study Registration Dates

• First Submitted: December 18, 2014
• First Submitted That Met QC Criteria: December 29, 2014
• First Posted (Estimate): December 31, 2014

Study Record Updates

• Last Update Posted (Estimate): December 31, 2014
• Last Update Submitted That Met QC Criteria: December 29, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Magnetic resonance imaging; Screening; Retinoblastoma; Second primary tumor
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Eye Diseases; Retinal Diseases; Neoplasms, Neuroepithelial; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms, Nerve Tissue; Eye Diseases, Hereditary; Eye Neoplasms; Retinal Neoplasms; Retinoblastoma
• Other Study ID Numbers: Rb-SPT-SCR