When Peggy Gronsdahl boarded a plane in Saskatchewan seven years ago, all she could do was hope. A doctor had told her three times that a strange reflection in her infant son’s eyes was nothing to worry about. Now, the eye had swollen to the size of a golf ball and he was being rushed to the Hospital for Sick Children in Toronto.

When they arrived in Toronto, Gronsdahl and her husband met Dr. Brenda Gallie and Dr. Helen Chan, an ophthalmologist and oncologist respectively, who specialize in retinoblastoma, a form of eye cancer that affects children shortly before or after birth. After conducting a number of tests, the doctors were afraid the cancer could spread, first to the optic nerve, then to the brain.

“Of course, I knew that something was wrong with my son’s eye. Not in my wildest dreams would I have imagined cancer,” Gronsdahl says. The doctors decided to remove Connor’s left eye. They met with the Gronsdahls, explained what the procedure would involve and started it shortly after. Halfway through, Dr. Chan emerged from the operating room to report that the cancer had not spread. But it wasn’t time to breathe relief quite yet.

As with all cancers, the success of treatment for retinoblastoma largely depends on the stage at which tumours are detected. Since retinoblastoma can be hereditary, the siblings and children of people who have had the disease require regular  surveillance so doctors can catch tumours if they start to develop. This meant Connor’s sister would have to undergo invasive  examinations under anaesthetic – less than ideal conditions for a procedure that must be performed on young children twice a year from the time they are born to age three or five. Children at risk for developing retinoblastoma may undergo as many as seven examinations under anesthetic in the first three years of life.

Connor’s ophthalmologist, Gallie, knew this was a problem. Luckily for the siblings and children of retinoblastoma patients around the world, she is in a position to do something about it: she is also a highly respected scientist.

In the 1980s, Gallie and other researchers at the Hospital for Sick Children conducted research on the gene that causes retinoblastoma, called RB1. The “retinoblastoma gene, RB1” a bit of a misnomer since its function is to suppress tumours – retinoblastoma occurs when RB1 is deactivated by a genetic mutation

Each retinoblastoma family has a different RB1 mutation, but the mutation is always the same within families with a history of retinoblastoma. This made it possible for Gallie to translate her research on RB1 into a test that predict before birth, which children will get tumors, which can then be destroyed by laser before they have a chance to grow.

The RB1 test can also rule out a patient’s chances of getting retinoblastoma. An economic study has shown that genetic testing would save money over the current surgery-based surveillance system. For the Gronsdahls, the discovery of the genetic mutation that caused Connor’s retinoblastoma had a tremendous impact. After drawing a single blood sample, doctors determined that Connor’s sister was not at risk of developing retinoblastoma, and she no longer needed to undergo invasive surveillance tests.

While most retinoblastoma children have significant visual impairment, the survival rate in Canada is high. There are, however, many challenges for affected families to access retinoblastoma care.  Most of these challenges relate to geography. Because first-line treatment for retinoblastoma is only available in Halifax, Montreal, Toronto and Vancouver, patients in the north and the Prairie Provinces travel a long way each month for specialized care.

There are fewer than 25 new cases of retinoblastoma each year, meaning few doctors have ever seen a case. Gallie notes that the level and quality of information-sharing throughout the country is uneven. Doctors have reported feeling excluded from the care of their patient once the child is admitted to hospital, and are not given the tools to deal with their patients when they return home. Sometimes, this means follow-up care that could be conducted at a doctor’s office is instead conducted in hospital, at greater expense and with greater disruption of the child’s life.

Gallie has joined forces with the Canadian Retinoblastoma Society, of which Gronsdahl is President, to draft the National Retinoblastoma Strategy to deal with regional disparities and other issues for retinoblastoma families. The Strategy addresses improvements that could be made along the cancer continuum, from detection, to genetic testing, to co-ordination of post-operative care.

Unlike other patient advocacy groups that seek to raise awareness among the general public, the Canadian Retinoblastoma Society’s first priority is targeted within the health care system.

“Public awareness is non-existent, but I don’t think that’s a huge problem, considering that we’re talking about a very rare disease,” says Emma Plant, 31, who was treated successfully by Gallie for retinoblastoma in infancy. She is now the Canadian Retinoblastoma Society’s treasurer. “Our concern is that the disease is so rare that in many cases, even physicians need more knowledge to be able to detect tumours in their early stages.”

Characteristically, Gallie has transformed this challenge into a goal. “We want to empower physicians with the knowledge they need to recognize the retinoblastoma so we can immediately get the referral and confirm the diagnosis while the cancer is in its earliest stages,” she explains.

“And just as important, once the diagnosis is made we want to keep them involved. Too often the case is simply handed off to the specialists. On our end, we need to keep the family physician informed during every stage of treatment so they are prepared to provide optimal care after surgery and chemotherapy.”

Since each case of retinoblastoma is unique, it is vital that family physicians receive information that is specific to the individual patient. Both Gallie and Chan try to keep in regular telephone contact with family physicians and specialists near the child’s home, sharing images and other information that will help them understand the status of the child. The Strategy seeks to use novel Internet medical conferences to facilitate this type of collaboration as a standard feature of retinoblastoma care in Canada, regardless of where the child resides.

 “Right now, there is some unevenness stemming from who the doctor is and where he or she is located,” explains Plant. “Specialists do what they can while the child is in hospital, but the follow-up care at the local level is a fundamental part of ensuring the child goes on to lead a normal, healthy life.”

Physicians aren’t the only group that Gallie wants to involve in the treatment of retinoblastoma. She says an important part of the national strategy is a greater role of parents, not just as passive caregivers but as decision-makers. She looks to the United Kingdom, which has special procedures for dealing with very rare diseases, as a model.

“In the special UK national program that sets resources for retinoblastoma, a parent representative is always at the table when they make decisions about retinoblastoma. In Canada we need to make that a normal part of the process, to see parental involvement as natural.”

An international force

As she works with the Retinoblastoma Society to harmonize treatment and resource standards across Canada, Gallie is also helping to tackle a much wider disparity. In Canada, retinoblastoma is essentially a curable disease: well over 95 per cent of patients survive to adulthood. In the less developed parts of the world, the opposite is true.

In less developed countries, there are very few specialists who deal with very rare diseases like retinoblastoma. Because there are generally fewer physicians per capita, they focus their efforts broadly and see more patients per day than the average Canadian doctor.

“Dr. Gallie is constantly sharing information with doctors in the developing world to help them treat patients,” explains OICR’s Deputy Director Dr. Bob Phillips, who worked with Gallie at the Hospital for Sick Children in the 1980s. “However, sometimes the only way she can save a child’s life is to treat them at the world-class facilities at the Hospital for Sick Children.”

To find a way to help retinoblastoma children outside Toronto, Gallie and Abby White, a retinoblastoma survivor in Oxford, UK, established Daisy’s Eye Cancer Fund, named for Daisy, a little girl in England who lost both eyes but whose family put up the first funds to help a child from Botswana. Daisy’s Eye Cancer Fund has ambitious goals. The current projects are a Global Registry of children with retinoblastoma worldwide and a multicentre clinical trial to evaluate the Toronto Protocol, a chemotherapy modification Chan and Gallie have devised that has proven successful at preserving many eyes affected by retinoblastoma.

A worldwide database has potential to benefit not just current patients, but also those of the future. Conventional clinical trials require hundreds, and often thousands, of patients to produce valid results; it is impossible to get scientifically significant results in a country where only 25 people get the disease each year. By keeping uniform data on each case in the world, scientists such as Gallie will be able to study and advance care for retinoblastoma in novel ways.

One of the rewards for splitting her time between surgery, one-on-one interaction with patients’ families, research, charity and leadership, is that work often comes around full-circle. This is what happened when Emma Plant had children. When Gallie invented the genetic test for retinoblastoma, there was a delay in getting it fully funded in Ontario. Confident that such details would sort themselves out based on strong scientific evidence, Gallie’s not-for-profit company, RB Solutions, performed the test anyway, at their own expense. The results showed that Plant’s daughter was not at risk.  

As for Connor Gronsdahl, he’s growing up happily in rural Saskatchewan. People who do not know him can’t even tell he has a prosthetic eye and he has good vision in the eye that was not removed. There is now one specialist in Saskatchewan familiar enough with retinoblastoma to conduct Connor’s semi-annual examinations: a pediatric ophthalmologist in Saskatchewan who was a fellow under Gallie several years ago. She would not, however, be able to treat retinoblastoma, and would not monitor children who are in active treatment.  

“I was oddly comforted by those trips to Toronto. Knowing that Connor was being examined by world leading specialists, and at the same time knowing these specialists would take time to talk one-on-one and even call me themselves if something needs to be brought to my attention, is truly the best of both worlds,” says Gronsdahl.