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    Selective techniques revolutionize treatment for retinoblastoma

    Intravitreal melphalan, intra-arterial chemotherapy provide high salvage rates

    Advances in treatment for retinoblastoma offer better safety than systemic chemotherapy and radiation and result in higher globe salvage rates without compromising patient survival, said Jonathan W. Kim, MD.

    “Intra-arterial chemotherapy is now rivaling systemic chemoreduction as a primary treatment modality for retinoblastoma, and intravitreal chemotherapy has replaced external beam radiation as a salvage therapy for vitreous seeding,” said Dr. Kim, director, Retinoblastoma Service, Children’s Hospital Los Angeles. “Treatment of extraocular retinoblastoma is also much different now as it is based on high-dose multiagent chemotherapy with stem cell rescue rather than deforming orbital surgery and radiation.”

    Intra-arterial chemotherapy

    Dr. Kim credited David Abramson, MD, of Memorial Sloan Kettering Cancer Center (MSKCC), New York, as a leader in developing the modern technique of direct ophthalmic artery infusion of melphalan. He worked with Dr. Abramson to salvage 7 of the first 9 treated eyes at MSKCC. Two eyes were removed due to persistent subretinal fluid, Dr. Kim said.

    Ocular oncologists at MSKCC have the largest experience with intra-arterial chemotherapy. In a series including almost 500 patients treated from 2011 to 2015, patients received a median of three infusions given at monthly intervals with a dose averaging 4 mg.

    “Their group reported a 29% incidence of Grade 3 neutropenia, and that speaks to the fact that melphalan is a very powerful drug and that some of it does get out into the systemic circulation,” Dr. Kim said.

    Figure 1. Retcam fundus photograph of the left eye of a 10-month-old child with unilateral Group D retinoblastoma. Courtesy of Jonathan W. Kim, MD

    In the series, 79% of patients avoided enucleation or radiation. Carol L. Shields, MD, of Wills Eye Hospital, Philadelphia, reported a 91% salvage rate in a series of unilateral Group D disease.

    “These outcomes compare favorably to the approximately 50% salvage rate associated with systemic chemotherapy alone,” Dr. Kim said.

    A paper by Yousef et al. that reviewed 12 published series of intra-arterial chemotherapy reported salvage rates of 66% overall and 57% in Group D/E eyes. This may be because most papers included in the review were older series whereas more recently, salvage rates are higher, Dr. Kim said.

    Intra-arterial chemotherapy complications include periorbital edema and erythema along with lash loss, all of which are transient. Rare, serious events include avascular retinopathy, sectorial choroidal vascular occlusion, and stroke.

    Data indicate the metastatic disease rate with intra-arterial chemotherapy is about 4%. “This rate is comparable to that reported for patients who have undergone enucleation even though intra-arterial chemotherapy is salvaging eyes with more advanced disease,” Dr. Kim said.

    Intravitreal chemotherapy

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