Study targets accurate diagnose, treatment of rare childhood eye cancer

In 2006, Dr. David Abramson helped introduce a way to treat childhood retinoblastomas by precisely injecting a small amount of a high-concentration chemotherapy directly to the eye’s single blood vessel.

Retinoblastoma is an eye cancer that begins in the retina — the sensitive lining on the inside of the eye. A rare form of eye cancer, it most commonly affects young children at age one or two, and may occur in one or both eyes.

Thanks to the intra-arterial chemotherapy, today 99 percent of babies with retinoblastoma can be cured. Yet accurately diagnosing the presence of retinoblastoma remains a significant challenge, said Dr. Abramson, the Chief of the Ophthalmic Oncology Service at the Memorial Sloan Kettering (MSK) Cancer Center in New York.

Dr. Abramson believes another existing technology – called MSK-ACCESS – can precisely diagnose and better guide the treatment of retinoblastoma. He is using a Gerber Foundation grant to validate that MSK-ACCESS, which is already in use at Memorial Sloan Kettering, can help to avoid common retinoblastoma diagnostic errors.

It is the cancer’s rarity – just 275 cases of retinoblastoma occur in the United States each year, and about 8,000 case worldwide – that contribute to the trouble of diagnosing it.

“Retinoblastoma has few, if any, symptoms at first,” Dr. Abramson said. It may be noticed if a pupil appears white when light is shined into the eye, sometimes with flash photography. Eyes may appear to be looking in different directions. Most of the time, he said, it is the parent who first notices something amiss.

And because retinoblastoma is rare and hard to diagnose – its clinical appearance varies and few clinicians have the experience necessary to consistently diagnose it correctly -worldwide almost one in five eyes surgically removed for suspected retinoblastoma are found to not have cancer. Fortunately, that has never happened at MSK.

Tissue biopsy for retinoblastoma is never done in a living patient because it is felt that the biopsy procedure itself can allow the cancer to spread beyond the eye. MRI can help with diagnosis but requires anesthetizing a very young baby, which can be challenging—and many physicians worldwide do not have access to MRI. In addition, it isn’t always helpful, as false positives and negatives do occur.

This is where Dr. Abramson believes MSK-ACCESS, which stands for Analysis of Circulating cfDNA to Evaluate Somatic Status, can be the difference. The MSK-ACCESS assay is a comprehensive liquid biopsy test that offers non-invasive cancer genomic profiling and disease monitoring.

It involves the deep sequencing of 129 key cancer-associated genes selected from MSK’s solid tumor genomic-profiling assay, MSK-IMPACT. MSK-ACCESS is designed to detect genetic alterations in cfDNA (cell-free DNA) specimens, such as blood and other body fluids.

The test’s sensitivity, Dr. Abramson said, can be compared to “being able to find a single misspelling in Tolstoy’s War and Peace.” Test results are available in three weeks using current technology.

In people with cancer, cfDNA may contain circulating DNA shed from dying cancer cells, which can be detected by the highly sensitive sequencing. Using MSK-ACCESS, molecular diagnosticians analyze cfDNA through a simple blood draw, providing a noninvasive way to profile the genomic characteristics of the underlying tumor.

Dr. Abramson has already published proof of concept for diagnosing retinoblastoma with MSK-ACCESS. He and his team also has demonstrated that the technology may reliably detect residual cancer, or its absence, within an hour after removal of a cancerous eye. These initial findings, if validated by the Gerber Foundation-funded project, means that MSK-ACCESS “could be immensely useful in guiding retinoblastoma treatment and improving outcomes,” he said.

His validation study, with its genomic sequencing method, will test sample blood specimens from known and enrolled patients to compare cancer-associated DNA alterations against “normal” DNA.

Dr. Abramson’s team has access to 300 blood specimens from retinoblastoma and retinoblastoma “look-alike” patients collected over the past several years, most of whom they have followed clinically. In years one and two they are analyzing 200 of these samples from 75 patients. Blood from 50 new patients, recruited in year two, will also be studied.

Now nearing the end of the first year of the three-year study, Dr. Abramson says that many of its aims already show promise.

“We know that most retinoblastoma tumors in the eye leaks into the blood, and that we can detect it. It also is clear, following removal of the eye, that retinoblastoma goes away very quickly; 90 percent is gone with 40 minutes and quickly goes down to zero when the cancer is not spreading,” he said. In cases of cancer metastases, “any levels in the blood can be found,” he added.

Worldwide, by improving retinoblastoma diagnosis, Dr. Abramson believes his project will prevent the unnecessary removal of babies’ eyes, and predict which, and when, babies will develop metastatic disease, thus enabling earlier, appropriate treatment and customizing management of the cancer.

“This work is directly focused on an outcome – on helping children,” he added. “That is our whole goal, to directly help children.”

He also extended his gratitude to the Gerber Foundation for its support.

“The Gerber Foundation, I want to thank and congratulate them for their support. This cancer is rare – just 275 cases in the US each year – but the foundation found it important enough to fund this research.

“That support, to me and my patients, is so incredibly important. This may not look as big as other cancers, but the funding is the fuel in my engine and the hope of a normal life for my patients,” he said.

Project Information:


David Abramson, MD - Board-certified ophthalmologist


Memorial Sloan-Kettering Cancer Center

Funded Research:

Non-invasive liquid biopsy for retinoblastoma to improve diagnosis and customize care for children