Multicenter Evaluation of Baseline MRI Screening With Extended Follow-up of Pineal Cysts for Early Detection of Pineoblastoma in Children With Retinoblastoma

1. INTRODUCTION AND RATIONALE Currently baseline brain MRI with extended follow-up of pineal cysts is systematically performed in all new retinoblastoma patients since children with hereditary retinoblastoma have an increased risk of primitive neuroectodermal tumors (PNET) that are histopathologically identical to the retinal tumors. This combination is also known as trilateral retinoblastoma (TRb). The prevalence of developing a PNET in combination with unilateral or bilateral hereditary retinoblastoma is 5-15%. The risk of developing TRb in Rb patients, is less than 0.5% for sporadic unilateral disease. The PNET usually arises in the pineal gland (PG) (77%) but can also be a parasellar or suprasellar tumor. A meta-analysis from 1999 including TRb patients from literature covering 1966 to 1998; they found that the interval between the ocular tumor and the intracranial tumor was 1 versus 22 months respectively in TRbs diagnosed in patients with screening versus patients who developed symptoms. Of TRb cases found at screening half were present when Rb was diagnosed and that 75% might be detected within one year after Rb diagnosis. Treatment is difficult and the prognosis is poor as only few survivors are reported. In a previous retrospective multicenter study from the ERIC-group small asymptomatic PNETs (<15 mm), that were present synchronously with the eye cancer (on baseline MRI) showed to have a better prognosis. Furthermore it was discovered that the majority of early stage pineoblastoma showed a cystic aspect, sometimes hardly distinguishable from benign pineal cysts (9,11,12). The prevalence of pineal cysts in hereditary Rb patients is 5.3%. In the general population at an age of 1 to 5 years 1.6% (1.1% in males and 2.2% in females) of all patients have pineal cysts. Current practice is based on evidence that early depiction of TRbs in retinoblastoma patients (during baseline MRI and follow-up of selected patients with pineal cysts) detects these aggressive tumors in a curable stage.
2. OBJECTIVES The main objective of this prospective multicenter study is to evaluate the current clinical strategy of baseline MRI screening of the brain in newly diagnosed retinoblastoma patients, with extended follow-up of selected patients with simple and complicated pineal cysts.

To investigate this objective the investigators will try to answer the following question: "What is the diagnostic accuracy (sensitivity and specificity) of the baseline MRI screening and extended follow-up of patients with pineal cysts for the diagnosis of TRb?" and: "How can the investigators optimize this screening strategy in order to minimise patient burden by keeping number of MRIs to a minimum and to maximise diagnostic accuracy?" The investigators will evaluate the classification (see section 3.7) of pineal cysts (probably benign versus suspicious) and pineoblastoma or supra- / parasellar PNET.

2.1 Secondary objectives

1. Evaluate epidemiological parameters:

2. incidence of TRb patients at baseline MRI (synchronous), follow-up (metachronous) MRI, and missed by MRI, compared to historical data;

3. survival of patients with positive TRb findings on MRI at baseline or follow-up compared to TRb patients missed by MRI and compared to historical data.

4. Evaluate prognostic parameters (age, tumor size, aspect, time of diagnosis relative to Rb diagnosis etc).

5. STUDY DESIGN The investigators propose a prospective multicenter cohort study (to investigate the diagnostic accuracy of baseline MRI screening of the pineal gland in new patients with retinoblastoma, with extended follow-up of selected patients with pineal cysts for early detection of pineoblastoma.