Retinoblastoma: A Deeper Look

How do children with the eye cancer retinoblastoma fare as they grow into adulthood? St. Jude researchers uncover answers.

Terry Aldridge was 8 months old in 1964, when his mom’s sister noticed a problem with his eye.

“My aunt was visiting and holding me,” Aldridge says. “She told my mother, ‘Ruth, there’s something wrong…There’s a white dot in the brown of his eye.’

 
Terry Aldridge

Terry Aldridge, who lost an eye to cancer in 1964, took part in a study of long-term retinoblastoma survivors from St. Jude. Like Aldridge, most of the participants work full time, live independently and have achieved other important milestones.

 

“So they rushed me to the doctor. He looked at me and talked to another doctor. That doctor told my mother, ‘That eye is going to have to come out today, or he might lose his other eye.’”

Aldridge had retinoblastoma, a cancer of the retina, the part of the eye that senses light and sends images through the optic nerve to the brain. Fifty years ago, when Aldridge arrived at St. Jude Children’s Research Hospital, treatment consisted of eye removal, chemotherapy and external beam radiation.

“They removed my left eye,” Aldridge explains. “I got my first prosthesis when I was 8 months old.

“I don’t feel I have any limitations,” Aldridge continues. “I’m not going to lie: I wish it hadn’t happened. But this is what happened, and I’ve had to live with it. I know I’ve been turned down from jobs on account of it—but I also know that I’ve been blessed.”

Good news for survivors

As one of the hospital’s early patients, Aldridge is among the older members in the St. Jude Lifetime Cohort Study (also called St. Jude LIFE), which follows St. Jude cancer survivors through adulthood. Aldridge’s experience is typical of most of the 69 adult retinoblastoma survivors who were evaluated in a recent study. Results of that study, which appeared in the journal Cancer, showed that most of those survivors have normal cognitive function, with the vast majority working full time, living independently and achieving other important milestones.

 
Tara Brinkman, PhD

Tara Brinkman, PhD, of St. Jude Epidemiology and Cancer Control, talks with a St. Jude survivor. “We know the visual system develops rapidly,” Brinkman says. Her recent study highlights the importance of early intervention and rehabilitation for children with retinoblastoma.

Earlier studies compared patients who had cancer in one eye to those with cancer in both eyes. But the St. Jude study looked deeper, says clinical psychologist Tara Brinkman, PhD, of St. Jude Epidemiology and Cancer Control. The child’s age at diagnosis—rather than the extent of disease—emerged as a crucial factor.

“Survivors diagnosed before 1 year of age performed better on measures of verbal intelligence, verbal learning, and short- and long-term memory,” Brinkman explains. “Verbal processing seems to be enhanced in survivors who were diagnosed younger than that age.

“We know the visual system develops rapidly,” she continues. “The earlier the disease appears, the greater the opportunity for the brain to adapt and compensate for disruption to the system. This highlights the importance of early intervention and rehabilitation for these children.”

Welcome surprises

Brinkman and her colleagues discovered that most of the long-term survivors in the study were doing well. Seventy percent of study participants were living independently, 62 percent were married or living with a partner, 58 percent had completed college or postgraduate education and 75 percent were employed full time.

In the areas of verbal intelligence, attention and memory, retinoblastoma survivors performed within normal ranges. Fine motor skills showed a dip, but in nonverbal reasoning and the ability to learn new information over a series of trials, the survivors were above the norm.

“It was a little bit surprising, given the very young age at which they’re treated and the fact that they receive intensive therapies, including surgery, chemotherapy and, historically, radiation therapy,” Brinkman says. “We expected that they might be at risk for some cognitive deficits. Generally, cancer survivors treated at a young age are at risk for cognitive or social difficulties later on, whereas this retinoblastoma group seems to be doing particularly well.”

A disease of the very young

Retinoblastoma is a cancer of early childhood. The eye tumor can even affect developing fetuses. The disease usually is diagnosed when a child is 1 to 2 years old, with the first noticeable sign often being a cloudy white pupil—a white-eye in a photo, rather than the normal red-eye effect. Today, as compared to when Aldridge was treated as a baby, retinoblastoma treatment can be finely focused, including chemotherapy injections and novel therapies.

 
Rachel Brennan, MD

“We want those survivors to live the fullest lives they can. So the treatment team is looking long-term, at the very edge of the horizon,” says Rachel Brennan, MD.

 

Rachel Brennan, MD, of St. Jude Oncology, has a particular interest in retinoblastoma, its therapy and late effects. She has treated children as young as 3 weeks old and as old as 10 years.

“With better than 95 percent survival rate when retinoblastoma is confined to the eye, you have to be extremely careful with the therapy,” Brennan says.

“You’re curing 2-year-olds who have decades of life ahead of them. With high survival rates, you want to make sure therapies can be tailored to the patient—to provide enough therapy but not over-treat. It’s a very fine line. Long-term, retinoblastoma survivors do very well. But the question is: For those who do not do as well, where are the deficits?”

The horizon’s edge

Brennan recently worked with St. Jude Psychology chair Sean Phipps, PhD, and others on the first-known study to follow developmental function of extremely young retinoblastoma patients. The results, published in the Journal of Clinical Oncology, were unexpected. Develop-mental functioning among the children, tested at 6 months and 1, 2, 3 and 5 years, slowly declined until age 5. Many of the 5-year-olds scored significantly below average. The decline was most pronounced in children whose treatment consisted solely of surgical removal of the eye, with no additional therapy. The researchers suspect that children who did not receive additional treatments may have had a reduced exposure to rehabilitative services.

Phipps and his team will conduct further studies to examine whether the declines continue over time, level off or lead to subsequent recovery.

“We are going to bring these kids back when they hit age 10 and assess them again,” Phipps says. “At that age, we can assess them in a much more finely grained way and look at issues such as attention and working memory, processing speed and other neuropsychological factors.”

 
Sean Phipps, PhD

Psychology chair Sean Phipps, PhD, and his colleagues are examining the developmental function of extremely young retinoblastoma patients.

 

Why is it important to study these patients on a long-term basis?

“A cancer survivor is a survivor for life,” Brennan says. “We want those survivors to live the fullest lives they can. So the treatment team is looking long-term, at the very edge of the horizon.”

St. Jude is using functional imaging to examine brain development and to evaluate how the brain compensates in the wake of retinoblastoma.

“We’re really trying to move our survivor projects forward,” Brennan says. “The psychology team is bringing the survivors back five years out. It’s no small task, so we want to be asking the right questions. I love this group of patients; I love the cooperation at St. Jude.”

Encouraging other survivors

The phenomenal thing, Brennan adds, is that the children compensate well. “They’re incredible,” she says.

And their parents?

“I trust these parents,” Brennan says. “A parent’s job is to know when something is wrong with their children and to advocate.”

Terry Aldridge couldn’t agree more about the importance of parents. “I was blessed to have a mother like mine, a great mother,” says Aldridge, who is now a father and grandfather himself. “She sacrificed for me.

“So, now, if there’s anything I possibly can do to help a mother and her child, I want to do it. I want to help. I tell them: ‘Be encouraged. Don’t give up. Have hope.’”

Abridged from Promise, Winter 2015

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