Conservative Treatments of Retinoblastoma

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.