A 45-year-old man with hereditary retinoblastoma (RB1 mutation carrier) develops bilateral retinoblastoma. Which agent is the preferred first-line systemic therapy to preserve vision while treating the intraocular disease?

Explanation

## Management of Bilateral Retinoblastoma **Key Point:** Intra-arterial chemotherapy (IAC) with melphalan is the preferred globe-salvaging approach for bilateral retinoblastoma, allowing preservation of vision while treating intraocular disease. ### Evolution of Treatment Strategy Historically, bilateral retinoblastoma was managed with enucleation (removal of both eyes) or external beam radiotherapy, resulting in blindness or secondary malignancies. Modern globe-salvaging approaches prioritize vision preservation. ### Intra-Arterial Chemotherapy (IAC) **High-Yield:** IAC delivers high-dose chemotherapy directly to the eye via the ophthalmic artery, maximizing tumor exposure while minimizing systemic toxicity. #### Mechanism and Agents - **Primary agent:** Melphalan (alkylating agent) - **Adjunctive agents:** Carboplatin, topotecan (often used in combination) - **Delivery:** Catheterization of the ophthalmic artery under anesthesia - **Efficacy:** Globe salvage rate >90% in many series for Group A–C eyes ### Comparison of Treatment Modalities | Modality | Mechanism | Vision Outcome | Complications | Role | |----------|-----------|----------------|---------------|-----------| | **IAC (Melphalan)** | Direct intra-arterial chemotherapy | Preserved in most | Retinal toxicity, cataract | First-line for bilateral | | **Systemic chemotherapy** | IV vincristine, doxorubicin, etoposide | Variable; requires adjunctive local therapy | Systemic toxicity, bone marrow suppression | Neoadjuvant or advanced disease | | **External beam RT** | High-energy photons | Blindness risk; secondary malignancy | Cataracts, retinopathy, orbital hypoplasia | Avoided in hereditary cases | | **Enucleation** | Surgical removal | Blindness (if bilateral) | Loss of eye; psychological impact | Reserved for salvage | ### Clinical Algorithm ```mermaid flowchart TD A[Bilateral Retinoblastoma] --> B{Intraocular<br/>extent?} B -->|Early/Intermediate<br/>Group A-C| C[Intra-arterial<br/>Chemotherapy] B -->|Advanced<br/>Group D-E| D{Salvageable?} D -->|Yes| E[IAC + Systemic<br/>Chemotherapy] D -->|No| F[Enucleation] C --> G{Response?} G -->|Good| H[Continue IAC<br/>± Systemic Chemo] G -->|Poor| I[Escalate to<br/>Systemic Therapy] ``` **Clinical Pearl:** Systemic chemotherapy (vincristine, doxorubicin, etoposide) is used as neoadjuvant therapy to shrink tumors before IAC or as adjunctive treatment in advanced cases, not as first-line monotherapy for intraocular disease. **Warning:** External beam radiotherapy is generally avoided in hereditary retinoblastoma (RB1 mutation carriers) due to the high risk of secondary malignancies (osteosarcoma, soft-tissue sarcoma) in the radiation field.