Retinoblastoma: Intravenous Chemotherapy

The last three decades have witnessed a dramatic evolution in the management of retinoblastoma, including classification schemes, treatment modalities, genetic testing, and screening. The current treatment model for retinoblastoma is to save lives, preserve the globe, and retain as much vision as possible. With the advent of intravenous chemotherapy, the use of external beam radiation therapy (EBRT) has been largely abandoned. The rationale for neoadjuvant intravenous chemotherapy is a reduction in intraocular tumor volume (chemoreduction) to allow better tumor cell killing with focal therapy (laser photocoagulation, cryotherapy, or brachytherapy). Eyes with Group A tumors are generally treated with focal therapy alone. Eyes with Group B tumors treated with three- to six-cycles of carboplatin, etoposide, and vincristine (CEV) in combination with focal therapy have resulted in ocular salvage rates of nearly 100%. Eyes with Group C or D tumors are treated with six-cycles of CEV chemotherapy in combination with focal therapy, with or without intravitreal chemotherapy. The recommended treatment for unilateral advanced tumors (particularly with extensive seeding) with no reasonable expectation for any useful vision (advanced Group D or Group E) is enucleation. The management of patients with high-risk histopathologic features on enucleated specimens has varied from close observation to, more commonly, adjuvant chemoprophylaxis with six-cycles of the low-dose CEV. Treatment options for extraocular retinoblastoma with overt orbital disease preauricular or cervical lymph node extension include intravenous chemotherapy and EBRT. The prognosis of patients with metastatic retinoblastoma without central nervous system (CNS) involvement is poor with conventional intravenous chemotherapy and radiation therapy alone; however, consolidation with high-dose chemotherapy with autologous stem cell transplant (ASCT) has improved survival outcomes. Lastly, metastatic retinoblastoma with CNS involvement (e.g., prechiasmatic lesion, CNS mass, and/or leptomeningeal dissemination) and trilateral retinoblastoma portends a poor prognosis despite aggressive multi-modality treatment, including intensive induction chemotherapy followed by consolidation with high-dose chemotherapy and ASCT. The contribution of EBRT is unclear in metastatic retinoblastoma with CNS involvement.