Retinoblastoma

What is retinoblastoma?

Retinoblastoma is a form of eye cancer that affects the cells of the retina. Diagnosis is relatively simple, but sometimes comes too late. The clinical signs, however, such as a white reflection in the pupil or a strabismus, are well known, and an ophthalmological exam of the optical fundus must be performed as soon as possible. Early diagnosis determines the use of treatments that will preserve vision.

Half of all retinoblastoma cases occur in individuals who are genetically predisposed to the disease. In these cases, the child carries a constitutional abnormality of the RB1 gene, meaning that there is a mutation in all of his or her cells. This abnormality puts the child at a very high risk (90%) of developing retinoblastoma.

If the inherited RB1 mutation is identified in a person with retinoblastoma, special consultations can take place to offer individual tests to any unaffected relatives (siblings, cousins, descendants) who may nevertheless carry the mutation. The aim of this is to carry out ophthalmological monitoring in a specialized environment to screen for possible occurrence of the disease at an early stage. Patients with a constitutional anomaly of the RB gene also have a significantly higher risk of developing secondary cancer than the general population (including sarcoma, pineoblastoma, melanoma, and glioma). Some of these secondary cancers may be caused by treatments of the retinoblastoma itself.

Treatment for this type of cancer at Institut Curie

Institut Curie is the leading treatment center for retinoblastoma in France and is one of the largest in the world. Multi-disciplinary care involves the following teams:

Ophthalmological Oncology
Pediatric Oncology
Anesthesia and ICU
Imaging
Anatomic Pathology (Biology of Tumors, Biopathology)
Genetic Oncology
Radiotherapy

Treatments are increasingly effective and differ according to the location and volume of the tumor, as well as the age of the child. The visual prognosis may be compromised, depending upon the location of the tumor and the impact of treatment on the retina.

Chemotherapy may sometimes be administered beforehand, to allow for possible conservative treatments (when the eye is spared). Several local treatments can then be offered:

Thermo-chemotherapy, which combines the action of a diode laser beam, which increases the temperature near the tumor, with that of chemotherapy.
Cryotherapy, which freezes the tumor several times by applying very low temperatures (-60° to -80°C).
Brachytherapy, which uses discs containing radioactive iodine grains to radiate the tumor locally.
New methods of administering localized chemotherapy are also possible nowadays, including intra-arterial chemotherapy into the ophthalmic artery (treatment given in partnership with the Rothschild foundation) and intraocular chemotherapy administered into the vitreous humor.
Conservative treatments that use external radiation (radiotherapy) are virtually never chosen these days due to the side effects, in particular the risk of secondary sarcoma in the radiated region.

The development of conservative treatments without external radiation significantly reduces the chances of surgical removal of the eye. However, enucleation often remains necessary for unilateral forms of the disease, and for one eye in bilateral forms of the disease.

Translational and basic clinical research on this type of cancer

In industrialized countries, the vast majority of patients suffering from retinoblastoma are cured. Efforts are therefore focused on reducing after-effects of the disease and treatments (preserving the child’s eyes and vision), better understanding of the mechanisms of tumor formation, and the discovery and improvement of existing treatments.

Clinical research is focusing both on implementing new conservative treatments and on post-operative treatments after surgical removal of the eye.

Rétino 2011 (conservative treatment)

RBSFCE2009 (non-conservative treatments)

Institut Curie is promoting two clinical trials (Rétino 2011 and RBSCFE 2009), with the statistic analyses conducted in the Biostatistics unit at Institut Curie. The children are all treated in close collaboration with the centers of the SFCE (French society to fight child and adolescent cancer).

In translational and basic research, Institut Curie has financed two incentive and cooperative research programs which have structured research into retinoblastoma.

The research projects are on the following topics:

Constitutional genetics - Claude Houdayer
The original cell of retinoblastoma - François Radvinyi
The development of new photo-dynamic treatments and their pre-clinical evaluation - Marie-Paule Teulade-Fichou
The development of new targeted treatments - Celio Pouponnot
Circulating biomarkers - Gudrun Schleiermacher

The Rétinostop association (French association to fight retinal cancer), founded in 1994, assists parents and children treated for retinoblastoma in childhood.

The team at Institut Curie is very much involved in the European Retinoblastoma Group (EURBG) in the fields of both care (European ERN certification) and research. This network also involves European parent associations.

In partnership with Retinostop and the AMCC, Institut Curie is also very involved in facilitating access to care for children with retinoblastoma in sub-Saharan Africa. Efforts are focusing on early diagnosis and treatments, if possible conservative ones, for these cancers.