Chemotherapy for retinoblastoma - A current topic

Retinoblastoma is the most common primary intraocular tumour in children. w ith an incidence of 1 in 15 000 live births. Treatment strategies for retin oblastoma have gradually evolved over the past few decades. There has been a trend away from enucleation (removal of the eye) and external beam radiat ion therapy toward focal 'conservative' treatments. Every effort has been m ade to save the child's life with preservation of eye and sight, if possibl e. Primary enucleation continues to be the commonly used method of treatment f or retinoblastoma. It is employed in situations where eyes contain large tu mours, long standing retinal detachments, neovascular glaucoma and suspicio n of optic nerve invasion or extrascleral extension. Most of these eyes eit her have or are expected to have no useful vision. Radiation therapy contin ues to be an effective treatment option for retinoblastoma. However, extern al beam radiotherapy has unfortunately been associated with secondary non-o cular cancers in the field of radiation (primarily in children carrying the RB-1 germline mutation). Ophthalmic plaque brachytherapy has a more focal and shielded radiation field, and may carry less risk. Unfortunately, its a pplicability is limited to small to medium-sized retinoblastomas in accessi ble locations. Cryotherapy and transpupillary thermotherapy (TTT) have been used to provide control of selected small tumours. TTT is an advanced lase r system adapted to the indirect ophthalmoscope which provides flexible non surgical treatment for small retinoblastomas. Recent research in the treatment of retinoblastoma has concentrated on meth ods of combining chemotherapy with other local treatment modalities (TTT, r adiotherapy, cryotherapy). This approach combines the principle of chemothe rapeutic debulking in paediatric oncology with conservative focal therapies in ophthalmology. Termed chemoreduction, intravenous or subconjunctival ch emotherapy is used to debulk the initial tumour volume and allow for focal treatment with TTT, cryotherapy and plaque radiotherapy. Cyclosporin has be en added to the chemotherapy regimen in several centres. Other clinical settings where chemotherapy is considered are situations whe n the histopathology suggests a high risk for metastatic disease and where there is extraocular extension. There is no consensus that chemotherapy is needed when choroidal invasion is observed on histopathology. However, in p atients where the retinoblastoma is noted beyond the cut end of the optic n erve or if there is disruption of the sclera with microscopic invasion of t he orbital tissue, treatment has been helpful. Systemic and intrathecal che motherapy with local and cranial radiotherapy has improved the survival of these patients. Most recently, the use of new chemotherapy modalities with haematopoietic stem cell rescue or local radiotherapy has increased the sur vival of patients with distant metastasis, Nevertheless, the prognosis of p atients with central nervous system involvement is still poor.