Retinoblastoma is the most common intraocular cancer in children. While more than 90 percent of children in the U.S. with eye cancers are cured, the outcome is not as good if the cancer has spread outside the eye. For two decades, intravenous chemotherapy was the mainstay of therapy, but it led to immunosuppression, infection, transfusions and increased risk of subsequent cancers.
“In advanced intraocular retinoblastoma, intravenous chemotherapy success rates were under 35 percent and came with significant toxicities,” said Anthony Daniels, M.D., director of ocular oncology at the Vanderbilt Eye Institute. “We knew there must be a better way.”
“We knew there must be a better way.”
Sparing Children from the Effects of Chemotherapy
Vanderbilt’s multidisciplinary ocular oncology team was one of the first to adopt intra-arterial chemotherapy (IAC), where chemotherapy is delivered into the ophthalmic artery through an endovascular microcatheter. The team has also incorporated intravitreal chemotherapy, in which the drug is injected directly into the eye.
Vanderbilt is currently the only center in the Mid-South and one of a handful in the U.S. offering both IAC and intravitreal chemotherapy for ocular cancer. The success rate has been high.
“Targeting the [ocular] tumor spares the rest of the child’s body from the toxic effects of chemotherapy,” Daniels said. “The increased efficacy of IAC is especially evident for eyes with more advanced disease, such as difficult-to-treat group D retinoblastoma. Since we began using these advanced therapies, we’ve successfully eradicated 100 percent of tumors.”
Adult Ocular Cancers
Daniels also treats adults with ocular cancers. “Uveal melanoma is by far the most common eye cancer in adults,” he said. “While we have excellent success rates for treating the intraocular tumor using implanted, plaque-based radiotherapy – almost 100 percent here at Vanderbilt – many patients end up losing vision as a result of this treatment, and many still go on to develop metastatic disease.”
Historically, eyes with large melanomas required enucleation (eye removal). A recent pilot study led by Daniels demonstrated that a technique called fractionated stereotactic radiosurgery (fSRS) could cure large uveal melanomas without enucleation. At the primary study endpoint of one year, 100 percent of tumors were successfully eradicated and 100 percent of eyes were saved. Most patients retained good visual acuity years after treatment.
None of the fSRS-treated patients developed metastases during the first three years of follow-up. “SRS allows us to save many eyes that previously would have been deemed unsalvageable because of the massive size of the melanoma,” Daniels said.
“SRS allows us to save many eyes that previously would have been deemed unsalvageable because of the massive size of the melanoma.”
For the roughly 33 percent of ocular melanoma patients who develop metastases, traditional chemotherapies have historically been ineffective, with average survival of six months. Daniels recently led a multicenter phase II study of a newly available immune checkpoint inhibitor, pembrolizumab, in patients with metastatic uveal melanoma. The small study demonstrated that pembrolizumab can have profound and durable clinical benefit for individual patients, especially if metastases are found early.
Discovering Novel Agents
Daniels’ laboratory research focuses on developing new, molecularly targeted therapies for ocular cancers. His lab has developed the first small animal model of intra-arterial chemotherapy to test the safety and efficacy of new chemotherapy compounds. They have also identified several agents that are just as effective as currently used regimens, but without the associated ocular toxicities.
“The problems I study are those that I see with my patients in clinic and in the O.R.,” Daniels said. “My discoveries in the laboratory are geared toward directly helping these patients and others with the same diseases.”