Chemotherapy is now the foundation of any globe-sparing regimen, either as a systemic intravenous treatment or as a selective intra-arterial modality.
Systemic intravenous chemotherapy typically includes 3–6 cycles of carboplatin, vincristine, and etoposide. This approach is highly successful in curing eyes classified as group A, B, or C when combined with local therapies, but it has only a 50% success rate in group D eyes. With chemotherapy, tumor regression occurs initially (chemoreduction), but adjunctive treatment with laser therapy, cryotherapy, and/or brachytherapy is necessary to completely treat the tumors; intravitreal injection of chemotherapy may also be needed to manage vitreous seeding (Fig 19-16). In addition, systemic chemotherapy often is given to patients with bilateral disease with at least IIRC group B or TNM group cT1b in the less affected eye. Although this treatment generally is well tolerated, even in very young children, complications can occur; these include cytopenia, ototoxicity, and potentially secondary acute myelogenous leukemia. Systemic chemotherapy without serial ophthalmoscopic examinations and without the use of adjunctive local therapies is not sufficient for treatment of intraocular retinoblastoma and may lead to extraocular spread and metastases.
Figure 19-16 Retinoblastoma. A, Appearance before systemic chemotherapy. B, Reduced tumor volume after 2 cycles of systemic chemotherapy alone.
Figure 19-17 Angiogram of an eye with retinoblastoma under fluoroscopy during treatment with intra-arterial chemotherapy. Arrow demonstrates the location of the microcatheter injection into the ophthalmic vasculature.
(Courtesy of Dan S. Gombos, MD.)
Due to the moderate success in treating more advanced eyes and systemic toxicities, local intra-arterial chemotherapy has gained popularity in the last 2 decades. Intra-arterial chemotherapy involves the selective infusion of chemotherapy into the ophthalmic artery via direct cannulation of the femoral artery (Fig 19-17). This modality usually involves administration of melphalan, topotecan, and/or carboplatin in 3 cycles. The effectiveness of intra-arterial chemotherapy is technique dependent and requires the expertise of an experienced interventional neuroradiologist. When this modality is used as primary therapy, cure rates of more than 90% have been reported for advanced-stage group D eyes. When it is used after previous treatment failure and tumor recurrence, the cure rate is approximately 50%. Intra-arterial chemotherapy typically is reserved for patients older than 3 months of age (>6 months in many centers) and/or at least 6 kg in weight. At some centers, intra-arterial therapy is reserved for children with unilateral disease; at others, tandem therapy is given to patients with bilateral disease.
Complications of intra-arterial chemotherapy include periorbital edema and erythema, nasal eyelash loss, a 3% per-infusion risk of ophthalmic vascular events (retinal nonperfusion, vitreous hemorrhage, subretinal hemorrhage, branch retinal vein occlusion, choroidal ischemia), and stroke. There is extensive debate about whether the risk for metastatic disease is increased in children with advanced retinoblastoma because of a lack of systemic chemotherapy. Most centers recommend adjuvant systemic chemotherapy after enucleation for children when pathologic evaluation of the globe reveals high-risk features for metastasis, such as massive choroidal invasion or tumor infiltration into the retrolaminar optic nerve. A recent COG study found that the highest risk for metastatic disease is the presence of concomitant peripapillary choroidal invasion of greater than 3 mm and postlaminar optic nerve invasion of 1.5 mm or greater, thus supporting adjuvant chemotherapy in this cohort. It should be noted that when eyes with advanced disease (which are more likely to have high-risk pathologic features) are salvaged, histologic information is not available to the medical team to prognosticate risk of systemic disease. For more information on the pathology of retinoblastoma, see Chapter 11.
Berry JL, Jubran R, Kim JW, et al. Long-term outcomes of group D eyes in bilateral retinoblastoma patients treated with chemoreduction and low-dose IMRT salvage. Pediatr BloodCancer. 2013;60(4):688–693.
Chévez-Barrios P, Eagle RC Jr, Krailo M, et al. Study of unilateral retinoblastoma with and without histopathologic high-risk features and the role of adjuvant chemotherapy: a Children’s Oncology Group study. J Clin Oncol. 2019;37(31):2883–2891.
Dalvin LA, et al. Ophthalmic vascular events after primary unilateral intra-arterial chemotherapy for retinoblastoma in early and recent eras. Ophthalmology. 2018;125(11):1803–1811.
Francis JH, Levin AM, Zabor EC, Gobin YP, Abramson DH. Ten-year experience with ophthalmic artery chemosurgery: ocular and recurrence-free survival. PLoS One. 2018;13(5):e0197081.
Excerpted from BCSC 2020-2021 series: Section 4 - Ophthalmic Pathology and Intraocular Tumors. For more information and to purchase the entire series, please visit https://www.aao.org/bcsc.