Conservative treatments of retinoblastoma (RETINO 2011)

1. -Multicentric non randomised, phase II study for the patients treated by chemoreduction (VP16, carboplatin) followed by chemothermotherapy without laser treatment at day 8
2. -Multicentric non randomised, phase II study for the patients with bilateral very asymmetric dis-ease (Group D eye on one of the eye) or unilateral presentation groups B/C/D according to the age and vitreous seeding
3. - Multicentric non randomised, phase II study for the patients treated by 6 cycles of three drugs regimen and local treatments for bilateral group D eyes or on the only eye.

Inclusion Criteria:

Study 1 inclusion criteria:

• Patients affected by unilateral retinoblastoma groups A, B (according to the age), group C (according to the age and vitreous seeding),or bilateral retinoblastoma groups A, B, C (excluding the eyes with macular threat and bilateral group D eyes or on the only remaining eye) amenable to a conservative treatment (at least on one eye in bilateral disease) but needing initial chemotherapy because of the location, the size of the lesion (more than 4 mm of diameter), a vision threat or risks of intravitreal relapse making those patients not amenable to chemothermotherapy first line.
• Patients less than six months of age with unilateral retinoblastoma groups B, C, D, or bilateral very asymmetric with one eye group D and the other amenable to local treatments without chemotherapy.
• Children from 0 to 6 years old.

Study 2 inclusion criteria:

• Patients affected by unilateral or bilateral retinoblastoma group B (according to the age), group C (according to the age and vitreous seeding), or group D.
• Patients affected by bilateral retinoblastoma very asymmetric with a group D eye that can be treated by intraarterial chemotherapy by Melphalan and the other amenable to local treatments without chemotherapy.
• Children from 6 months to 6 years old.

Study 3 inclusion criteria:

• Children affected of bilateral group D retinoblastoma or on the only eye amenable to conservative treatment.
• Children from 0 to 6 years old.

Common inclusion criteria:

• Patients not previously treated by chemotherapy or radiotherapy for this tumour or another cancer.
• No contra-indications to the study treatments
• Possible long term follow-up.
• Written informed consent of the parents or the legal representative.
• Patients having social security cover.

Exclusion Criteria:

Study 1 exclusion criteria:

• Patients for whom a local treatment is possible without initial chemotherapy (tumour smaller than 4 mm and located far from optic nerve head or macula).
• Patients with an unilateral group D with massive tumour or group E eyes needing enucleation first line or after initial chemotherapy (in case of buphthalmia or suspected optic nerve invasion or extrascleral extension).
• Patients affected by bilateral retinoblastoma very asymmetric with a group D eye that can be treated by intraarterial chemotherapy by Melphalan and the other amenable to local treatments without chemotherapy.
• Patients with bilateral retinoblastoma and bilateral group D eyes or on the only remaining eye or presenting a bilateral macular threat requiring conservative treatment by a 6 cycles, three drugs regimen.

Study 2 exclusion criteria:

• Patients with a unilateral group D (extensive) or B or C but covering the optic nerve head or group E eyes for which enucleation is warranted first line or after chemotherapy (in case of buphthalmia or suspected optic nerve invasion or extrascleral extension).
• Patients with unilateral group D eye with tumour volume of more than 50% of eye volume, for whom a massive choroidal invasion could be associated (on clinical or imaging criteria) and for which enucleation is warranted.

Study 3 exclusion criteria:

• Patients for whom a local treatment is possible without chemoreduction (tumour smaller than 4 mm, distant from macula and from optic nerve head).
• Patients affected by bilateral retinoblastoma very asymmetric with a group D eye that can be treated by intraarterial chemotherapy by Melphalan and the other amenable to local treatments without chemotherapy.
• Patients with bilateral retinoblastoma without macular threat or groups A, B, C than can be treated with chemoreduction by VP16 and Carboplatin then chemothermotherapy without laser at day 8.

Common exclusion criteria:

• Patients older than 6 years old.
• Patients with extraocular retinoblastoma.
• Patients with a disease being a contra-indication to chemotherapy.
• Patients anteriorly treated by chemotherapy.
• Patients anteriorly treated by external beam irradiation.
• Patients anteriorly treated for another cancer.
• Follow-up not possible due to geographic distance from the center or for social or psychological reasons.
• Parents not having accepted the therapeutic strategy after explanations by the investigator.
• Contra-indication to the use of one of the drugs used in the study.

Sponsor will share de-identified data sets. Documents generated under the project will be disseminated in accordance with Institut Curie policies.

Data requests can be submitted starting 9 months after last article publication and will be made accessible for up to 12 months.

Access to trial individual participant data can be requested by qualified researchers engaging in independent scientific research, and will be provided following review and approval of a research proposal and Statistical Analysis Plan (SAP) and execution of a data sharing agreement (DSA).