A Shared Vision

Three-year-old Hannah Williams likes to play doctor with her doll, Sweetie. But unlike other girls her age, Hannah knows what her doll is feeling when she administers shots, takes her temperature and gives her “sleep medicine.” She is always gentle with Sweetie, reassuring her that “it will be okay; it won’t hurt,” especially when she has to do something to Sweetie’s eyes.

When Hannah was 13 months old, a swinging door accidentally hit her head. In one day, her parents went from thinking their daughter had a lazy eye to torn retinas to bilateral retinoblastoma, a fast-growing cancer of the retina that can be fatal.

“In all my 38 years, I never could have fathomed what I felt the minute we were told our baby had cancer,” Missy Williams says. “All the breath in my body just fell away.”

Hannah’s family had noticed a strange, white reflection that appeared in one of her eyes in photographs. “Everyone’s eyes would be red from the flash except for that one eye, or there would be a white speck on her eye that we thought was just dust on the lens,” Missy explains. But the healthy, happy little ball of fire seemed to have no vision problems, so her parents had not mentioned the spot to Hannah’s pediatrician.

Unanswered questions

Unilateral retinoblastoma is a malignant tumor that occurs in one eye. The treatment for children with unilateral disease is simple: the eye with the tumor is removed and if the cancer has not spread, the child does not need follow-up treatment.

Bilateral retinoblastoma can occur in one or both eyes and can involve one or dozens of tumors. In this kind of retinoblastoma, tumors may break away from the main mass like seeds blown from a dandelion and remain suspended in the fluid of the eye called the vitreous. These tiny tumors, or “vitreous seeds,” can be difficult to treat; in the gel-like vitreous they move and spread the way mercury spilled from an old thermometer divides into countless balls of silver.

Twenty-five percent of children diagnosed with bilateral retinoblastoma inherit the mutated gene from their parents. The other 75 percent develop it before birth. Although treatments for the disease have improved tenfold in the last several decades, many unanswered questions remain.

Hannah Williams did not inherit bilateral retinoblastoma from her parents; she developed it in utero. If she has children, they will have a 50 percent chance of developing the disease. Sadly, children with bilateral retinoblastoma have a 40 percent chance of developing other primary cancers.

“Retinoblastoma is the most clear-cut hereditary cancer in the human body,” explains Barrett Haik, MD, director of the St. Jude Eye Clinic. “Some may ask: Why worry about a disease that only affects 200-300 kids a year? Well, it’s the only tumor where you have such a clear genetic predisposition. It was one of the first cancer genes cloned, and if there is ever going to be gene therapy, retinoblastoma is going to be the disease that’s going to be well suited for it."

Seeking answers

Carlos Rodriguez-Galindo, MD, of Hematology-Oncology is leading a multidisciplinary team that is developing a retinoblastoma protocol slated to begin this summer. The study is designed to determine the best treatment for children with the disease, to further study the biology of the disease, to discover why some children develop the disease in utero and to determine how children with retinoblastoma think and learn.

For decades, retinoblastoma was treated primarily with enucleation (eye removal) or radiation. The new protocol will test the chemotherapy drugs topotecan and vincristine, which are often used in conjunction with lasers, freezing techniques and implantation of radioactive seeds, especially for cases of more advanced disease. The goal is to prevent enucleation and to avoid or delay radiation therapy, which has many negative side effects for children who are growing and developing. 

“Right now, we are saving some 70-80 percent of the eyes, but we still have to irradiate maybe 30-40 percent of them,” says Rodriguez-Galindo. “We want to take that number way down.” Currently, enucleation and radiation are the only ways to treat vitreous seed tumors. 

The protocol will also explore the cognitive development of children with retinoblastoma. “There is a lore about kids with retinoblastoma that they are above average in intelligence,” says Sean Phipps, PhD, Behavioral Medicine. “This is curious when you consider that some will have impairments or have faced invasive therapies at a very young age. To date, this is just a clinical impression and has not been rigorously tested. This study gives us a unique opportunity to examine the neuropsychologic development of children with retinoblastoma, and to explore possible factors associated with their high level of functioning.”

Many St. Jude patients are also involved in a protocol led by a team at Children’s Hospital in Philadelphia. The multi-institutional study involves blood tests and questionnaires filled out by parents of affected children.

“We are interested in finding out why 75 percent of these children develop the mutation in utero,” says Rodriguez-Galindo. “Are there environmental factors? Are welders or smokers, for example, more apt to have children with retinoblastoma? There have been a few documented reports, a few patterns, but nothing consistent. We know there are some ethnic differences: people of native-American ancestry, those in Central America, and those of more native backgrounds along the North and South America continents have higher incidences of retinoblastoma. Socioeconomic conditions also seem to play a role. But the questions remain, and we hope to find more solid, consistent answers.” 

Rodriguez-Galindo attributes much of the program’s current success and knowledge to the late Charles Pratt, MD, a senior pediatric oncologist at St. Jude, who treated patients for more than 30 years and was the primary designer of the hospital’s current protocols.

“Sometimes things come out of studies that you don’t expect,” says Stephen Skapek, MD, Hematology-Oncology, who is also involved in the Philadelphia protocol. “Sometimes you learn through secondary markers, not through the ‘ah-ha’ answers. It’s an important study. Sometimes it is hard to put all the pieces together to get answers, but you have to try.”

With a disease like bilateral retinoblastoma come the difficult genetic questions. If a child has this cancer, do the parents want to be tested? What will they do with this information? Will they share genetic details when their children are older?

“We are concerned about the lack of communication when it comes to retinoblastoma,” says Rodriguez-Galindo. “For example, we recently had two new babies here with retinoblastoma. Both had affected parents. None of them was aware that they would pass it on to their children.

“Maybe people block out this information, or the parents or grandparents die so the later generation never knows about the genetic history. Or maybe parents don’t want to tell their kids, and 20 years later they have forgotten or they think it’s better to forget. These kids need to know their genetic history. They also need to know that they have a 40 percent chance of developing another cancer. Retinoblastoma is the genetic syndrome with the highest risk of cancer.”

Looking ahead

A spunky little preschooler, Hannah Williams looks no different from any other girl her age. Even her hazel-green eyes don’t give her away—one real, the other created just for her. Because Hannah’s disease was advanced at the time of diagnosis, she lost her right eye. She endured two rounds of chemotherapy, and the tumors in her left eye were also treated.

Missy Williams says she will have some serious talks with her daughter when she is older. She will tell Hannah that she has a high chance of developing another cancer or passing the mutation to her own children. 

For now, Missy and her husband are concentrating on the present. “Nothing gets in Hannah’s way,” says Missy. “And we try never to hinder her. We always encourage our little angel baby to try anything—to accomplish whatever is in her head and heart.”

Reprinted from Promise magazine, spring 2004

 

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