Analysis of histological risk factors and biomarkers in paediatric retinoblastoma

Prior treatment

• Study A: 3. Unilateral retinoblastoma with indication of primary chemotherapy before enucleation: • Large buphthalmos, aseptic orbital cellulitis and/or raised intraocular pressure depending on local practice • Extraocular extension • Radiological criteria suggesting retrolaminar extension associated with a risk of invasion of surgical margin • Radiological criteria suggesting extrascleral extension • Lymph node involvement confirmed by pathological or cytological analysis

Other illness

• Study B: 4. Uncontrolled medical conditions, psychological, familial, sociological or geographical conditions that could impede compliance with the protocol
• Study A: 6. Uncontrolled medical conditions, psychological, familial, sociological or geographical conditions that could impede compliance with the protocol
• Study B: 2. Metastatic extension at diagnosis: any lymph node extension, “distant” haematogenous locations (such as bone/ bone marrow, lung, liver…), any CNS extension outside pre chiasmatic optic nerve involvement (such as optic chiasm invasion, meningeal disease…)

Other

• Study A: 1. Bilateral and/or familial or trilateral retinoblastoma
• Study B: 3. Non-compliance with any of the inclusion criteria
• Study B: 5. Participation in any other interventional study within 1 year after the end of treatment in the present study (except in the event of early relapse of retinoblastoma)
• Study A: 2. Absence of diagnostic-quality orbital and CNS high-resolution MRI before enucleation
• Study A: 4. Unilateral retinoblastoma amenable to conservative treatment
• Study A: 5. Metastatic extension at diagnosis
• Study A: 7. Participation in any other interventional study within 1 year after the end of treatment in the present study (except in the event of early relapse of retinoblastoma)
• Study B: 1. Bilateral and/or familial or trilateral retinoblastoma

• Study A: 1. Written informed consent and assent (when age appropriate), obtained in accordance with institutional or national guidelines
• Study B: 2. Patients with unilateral retinoblastoma with buphthalmos (group E/stage cT3c), and/or raised intraocular pressure (stage cT3c), or aseptic orbital cellulitis (stage cT3e) (depending on local practice), OR Patients with unilateral retinoblastoma with radiological evidence of extraocular disease with obvious retrobulbar optic nerve involvement, thickening of optic nerve or orbital involvement, i.e. stage cT4a, or with extraocular tumor clinically evident with proptosis and/or orbital mass, i.e., cT4b.
• Study B: 3. No prior chemotherapy or radiotherapy for retinoblastoma or other tumor types
• Study B: 4. No medical contraindications to the treatment as planned
• Study B: 5. Patients must have adequate organ function: Adequate hematopoietic function: - Neutrophils > 1.0  109/L - Platelets > 100  109/L Adequate renal function: - Serum creatinine < 1.5  ULN for age with normal creatinine clearance estimated by Schwartz formula Score < Grade II on Brock ototoxicity grading scale Normal left ventricular function on echocardiography in patients who are to receive high-dose chemotherapy
• Study B: 6. Serum pregnancy test (for subjects of childbearing potential) negative within 72 hours prior to first dose of study administration.
• Study B: 7. Women of childbearing potential (WOCBP) must agree to use a highly effective method of contraception during the screening period, during the treatment of the study and at least 6 months after the last administration of study treatment. It is strongly recommended for the male partner of a female subject to also use male condom plus spermicide throughout this period.
• Study B: 8. Patients for whom long-term follow-up is possible
• Study B: 9. Patients covered by national health insurance, depending on country-specific regulations.
• Study A: 2. Patients with extensive non-familial unilateral intraocular retinoblastoma requiring primary enucleation
• Study A: 3. No prior chemotherapy or radiotherapy for retinoblastoma or other tumor types
• Study A: 4. No medical contraindications to post-operative chemotherapy
• Study A: 5. Patients must have adequate organ function: Adequate hematopoietic functions: - Neutrophils > 1.0 x 109/L, - Platelets > 100 x 109/L Adequate renal function: - Serum creatinine < 1.5 ULN for age with normal creatinine clearance estimated by Schwartz formula Score < Grade II on Brock ototoxicity grading scale. Normal left ventricular function on echocardiography < Grade 2 NCI CTC. Adequate liver function < Grade 2 NCI CTC: - Total bilirubin ≤ 1.5 times upper limit of normal (ULN) for age, unless the patient is known to have Gilbert’s syndrome - ALT, AST < 3 x ULN - ALP < 2.5 X ULN for age
• Study A: 6. Serum pregnancy test (for subjects of childbearing potential) negative within 72 hours prior to first dose of study administration.
• Study A: 7. Women of childbearing potential (WOCBP) must agree to use a highly effective method of contraception during the screening period, during the treatment of the study and at least 6 months after the last administration of study treatment. It is strongly recommended for the male partner of a female subject to also use male condom plus spermicide throughout this period.
• Study A: 8. Patients covered by national health insurance, depending on country-specific regulations.
• Study B: 1. Written informed consent and assent (when age appropriate), obtained in accordance with institutional or national guidelines