Detecting infant eye cancer advancing in SoCal

When Kaleb was born in late 2014, his mother was thrilled that he didn’t have any tumors in his eyes.

The disease was — and remains — a real risk for the 4-month-old because his mom, Jessica Learned, and her two daughters have the hereditary eye cancer called retinoblastoma.

When Learned herself was 18 months old, doctors discovered a tumor. She had one eye removed. “It was pretty far gone,” she said. “It had overtaken the entire eye.” Learned also went through extensive radiation on her other eye.

Then her eldest daughter, Karley, now 7, was detected with an eye tumor while she was still in utero. The cancer was so far advanced that surgeons had to remove the infant’s eye shortly after she was born.

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Learned’s second child, KayLinn, developed eye tumors as an infant. Luckily, they were caught early enough so she hasn't lost an eye. But still, 4-year-old KayLinn suffers from bad vision.

“She has to have pretty thick lenses,” Learned said.

Recently at Children's Hospital Los Angeles, Learned watched as Kaleb was wheeled into the operating room for his second eye exam under anesthesia, and all she could do was wait.

Cancer that robs a patient's vision

Retinoblastoma occurs when one of the two copies of the RB1 gene is broken or mutated. If a parent has retinoblastoma, his or her children have a 50 percent chance of inheriting the mutated gene. This type of cancer develops in the first 24 months of life and is a common form of pediatric cancer.

The risk of retinoblastoma is greatest for children with a family history of the cancer, according to Dr. Pedro Sanchez, medical geneticist and director of Cytogenomics at Children’s Hospital Los Angeles.

“For all other children, the risk is one in 15,000,” he said. Pediatricians screen newborns and at every well visit by shining a light in a child’s eyes to find developing tumors.

Kaleb Learned, while clear of eye tumors at birth, falls into the high-risk category due to his mother's retinoblastoma. As a result, he must undergo frequent eye exams, performed under anesthesia, so doctors can get to any developing tumors as early as possible.

This is how many children with familial retinoblastoma are monitored and diagnosed nationwide.

But with medical advances, it is now possible to diagnose this pediatric cancer before tumors even appear, thanks to a diagnostic tool called gene sequencing.

“Early diagnosis equals earlier treatment which equals greater likelihood of saving vision,” Sanchez said. His team at Children’s Hospital is helping to chart advances in retinoblastoma diagnosis and treatment. Expert clinicians paired with new technology can sequence a child’s entire retinoblastoma gene and definitively establish a patient's chances of developing the eye cancer.

Last year, 280 children were diagnosed with retinoblastoma in the United States. Globally, about 8,000 children are diagnosed each year. In the U.S., nearly 95 percent of retinoblastoma patients are cured. That's significantly better than in developing countries, where 90 percent of retinoblastoma patients don't survive. It's also a big improvement from the 1960's ago when 18 percent of American children died. 

Delivering personalized medicine

What Children’s Hospital is doing falls under the umbrella of personalized medicine.

Through advanced genetic analysis, it is now possible to learn whether inherited mutations of certain genes point to a higher risk for disease. Through personalized medicine (also known as “precision medicine”), more individualized treatments or drugs can be administered.

“Part of the goal of personalized medicine is giving people counseling and a timeline of when they should be evaluated and how we could customize their medical treatment plan,” Sanchez said.

For infants like Kaleb Learned, that could mean the difference between greatly impaired vision — like his mother's and two older sisters' — or early treatment to keep his vision as close to normal as possible.  

The process of determining whether Kaleb’s RB1 gene is normal or has a mutation began with a blood draw, done as he was under anesthesia while being examined for tumors.

The blood sample was then taken from the Children’s Hospital's operating room to the building right next door that houses the high-tech machines, robots and clinical staff. There, staff using the advanced technology extracts DNA, sequences and tags individual strands of DNA, and analyzes the specimens.

It’s a complicated task, according Gigi Ostrow, manager of molecular diagnostics at Children’s Hospital, who runs the labs where the genetic sequencing takes place.

“What we’re looking at here with the entire RB1 gene is the equivalent of about 11 copies of 'War and Peace,'” she said. “This is a huge gene.”

The lab uses robots to carry out the DNA extraction. “It can take the blood or any other specimen, and, using tiny magnetic beads, pull out the DNA, [and] wash it so that it's clean and ready for analyzing,” Ostrow said.

“This is basically the face of the future practice of medicine,” said Dr. Timothy Triche, director and founder of the Personalized Medicine Center at Children’s Hospital.

“We’re going to be using very precise information, like we’ve never had before, and the long-term goal is to apply these tools not just to retinoblastoma, but to basically all the children that are seen at Children’s Hospital,” he said.

Outside the hospital operating room, Jessica Learned nervously waits to hear the results of Kaleb's eye exam under anesthesia. Finally, pediatric surgeon Dr. Jonathan Kim walks up with the news:

"So Kaleb is a week shy of being four months old and both eyes look completely normal today," he said. "So that's good news."

Learned is relieved, but she knows her son could still develop tumors. Results of the genetic sequencing, which will tell her for sure if Kaleb can live a life free of eye cancer, are due before the end of April.