Chemotherapy in Retinoblastoma: Current Approaches

Abstract

Retinoblastoma (RB) is the most common childhood malignant intraocular tumor. Although enucleation and external beam radiotherapy have been historically used, today the most commonly used eye-sparing approach is chemotherapy. Chemotherapy can be used in both intraocular and extraocular RB cases. Chemotherapeutic agents may be applied in different ways, including systemic, subconjunctival, intra-arterial and intravitreal routes. The main purposes of application of systemic therapy are to reduce the tumor size for local treatment (chemoreduction), or to reduce the risk of metastasis after enucleation surgery (adjuvant therapy). Intra-arterial chemotherapy with the current name "super-selective intra-arterial infusion therapy" could be applied as primary therapy in tumors confined to the retina or as a secondary method in tumor recurrence. The most important advantage of intra-arterial therapy is the prevention of systemic chemotherapy complications. Intravitreal chemotherapy is administered in the presence of persistent or recurrent vitreous seeding. The term "extraocular RB" includes orbital invasion and metastatic disease. Current treatment for orbital invasion is neoadjuvant chemotherapy followed by surgical enucleation and adjuvant chemotherapy and radiotherapy after surgery. In metastatic disease, regional lymph node involvement, distant metastases, and/or central nervous system (CNS) involvement may occur. Among them, CNS involvement has the worst prognosis, remaining at almost 100% mortality. In metastatic disease, high-dose salvage chemotherapy and autologous hematopoietic stem cell rescue therapy are the possible treatment options; radiotherapy could also be added to the protocol according to the side of involvement.

Keywords: Retinoblastoma; chemoreduction; intra-arterial chemotherapy; intravitreal chemotherapy; subconjunctival chemotherapy.

Figure 1. Leukocoria in retinoblastoma

Figure 10. T1-weighted orbital magnetic resonance imaging of retinoblastoma-related buphthalmic bulbus oculi and orbital invasion

Figure 2. A long (~15 mm) optic nerve resection in enucleation. Due to retinoblastoma extension into the central nervous system through the optic nerve, a long resection can be life-saving

Figure 3. A) Macular retinoblastoma before chemoreduction. B) Tumor focus shows complete regression after 6 cycles of chemoreduction

Figure 4. Partial regression after chemoreduction and type IV chorioretinal scar due to cyrotherapy

Figure 5. Regressed calcific retinoblastoma focus (type I regression pattern) after chemoreduction

Figure 6. Anterior segment seeds found at initial presentation in a case with group E retinoblastoma according to the International Retinoblastoma Classification System

Figure 7. Subconjunctival carboplatin administration

Figure 8. Checking retinal staining (arrows) by the injection of radio-opaque material through a microcatheter placed in the ostium of the ophthalmic artery (*) prior to intra-arterial chemotherapy administration

Figure 9. Intravitreal melphalan injection. (A) The pars plana area was marked with a gauge (3 mm from the limbus in accordance with the patient’s age); (B) after intravitreal injection, freeze-empty cryotherapy was applied three times during withdrawal of the 30-G injector; (C) paracentesis was performed due to elevated intraocular pressure; (D) freeze-empty cryotherapy was applied three times to the limbus during withdrawal of the paracentesis injector