Genetic based tests help doctors tailor treatment for kids with brain tumours

Research had shown that pediatric gliomas with this genetic signature often respond well to a drug used to treat adults with malignant melanoma, a potentially deadly form of skin cancer. (Pixabay photo, CC0 Creative Commons)

TORONTO—At eight years old, Julia Van Damme was like most other kids her age — going to school, playing sports and goofing around with her younger sister and older brother. But a routine eye exam turned up a baffling and unexpected finding — she was virtually blind in one eye.

An MRI showed Julia had a golf ball-sized tumour in her brain, and the pressure it was exerting on her optic nerve was destroying the sight in her left eye.

“I didn’t notice I was losing vision at all, because I was young,” said Julia, now 12. “I didn’t know what a brain tumour was. I didn’t know what cancer was then, so it was pretty hard for me to understand.”

A biopsy of her tumour at Toronto’s Hospital for Sick Children determined Julia had what’s known as a low-grade glioma, a pediatric brain cancer that affects about 25,000 to 30,000 children worldwide.

Because of its location in the centre of her brain, above the pituitary gland, the tumour couldn’t be removed surgically, and radiation in the area carried too high a risk of long-term effects. So Julia was started on standard chemotherapy, a gruelling 18-month course of weekly intravenous infusions, which in the end was ineffective in shrinking her tumour.

But doctors at Sick Kids had another trick up their proverbial sleeves: tests they had developed to analyze the molecular makeup of individual brain tumours showed Julia’s cancer was being driven by a single genetic mutation called a BRAF (pronounced bee-raf) V600E.

Research had shown that pediatric gliomas with this genetic signature often respond well to a drug used to treat adults with malignant melanoma, a potentially deadly form of skin cancer.

For almost two years, Julia has been able to keep her tumour from progressing by taking two pills in the morning and two at night — an oral regimen that was unheard of just a few years ago.

“In the past, we used to treat kids with brain tumours just based on looking at the tumour, by how the cells looked (under a microscope) and by looking at the imaging,” said Dr. Uri Tabori, a neuro-oncologist at Sick Kids. “We did all tumour types sort of the same.”

But in the last decade, researchers began to be able to delineate tumours into subtypes based on their genetic profile, allowing them to predict how each subtype was likely to behave given a specific treatment.

“Then we realized that using these molecular tools, we can actually tailor treatment to some patients that’s different than others,” said Tabori, who treated Julia.

“We can say for your tumour, it’s going to be very, very low-grade, slow-growing, and we should refrain from any toxic therapy. And for the other ones, we need to be more aggressive.

“And the last part of that, which is amazing, is that some tumours will actually have pills that target the mutation. So instead of giving chemotherapy, radiation and aggressive surgery, you can just give the pill and the tumour will respond and the patient will get better.”

Dr. Cynthia Hawkins, a neuropathologist at the hospital, has been at the forefront of developing the molecular tests to help doctors better diagnose and treat specific subtypes of childhood brain cancers, among them glioma and medulloblastoma, a fast-growing malignancy that accounts for about 20 per cent of all childhood brain tumours.

“One of the issues that we run into with pediatric brain tumours, in particular, is that although some commercial entities have developed tests for adult brain tumours, most of them don’t do it for pediatrics because the numbers just aren’t big enough to make it financially viable,” Hawkins explained.

“And most of these tests we had to develop from the ground up at Sick Kids,” she said, adding that hospitals across Canada, as well as from the U.S. and countries around the world now send tumour samples to the Toronto hospital for molecular analysis.

While Julia is doing well — the oral medication Dabrafenib initially shrank her tumour by about 15 per cent and its size has since stabilized — her diagnosis sent the Mississauga, Ont., family on a journey they never expected to take.

“We were shocked,” said her father, Dan Van Damme, especially since Julia had never indicated she was having trouble seeing, had an A average at school and had continued to play soccer and hockey, even sometimes taking a turn as a goalie.

Even through her weekly rounds of chemo, Julia maintained an upbeat demeanour, said her mother Maureen. “She’s a trooper, she’s a tough kid and she never complained about ‘Why her, why do I have to do this?’

“She was always smiling. We’d skip down the hallways to go get chemo,” she recalled. “She just has such a strong spirit and a great attitude.”

Before Julia went into the hospital to have a biopsy of her tumour, her brother Dylan, now 14, and sister Clara, 9, went up to their rooms and each brought her a stuffed animal to take with her.

“The bond the three of them made and the five of us made during this journey is ‘We’re in it together,”’ said Maureen, a stay-at-home mom. “That was from Day 1 our motto: we’re in this together, you’re not alone.”

“I think you realize when something like this happens to you what’s most important in life,” added Dan, who’s a salesman for LinkedIn. “We have a different outlook. Our family is this stronger unit, and we really focus on activities that we can do together as a family all the time.”

As for their daughter, she has her sights set firmly on the future.

“There’s always something to look forward to,” said Julia, who seems mature beyond her years. “When I’m going through something tough, I think about what’s going to happen in the future. And once I finish this (treatment), it’s done.

“So it’s better for me to think about what’s going to happen later on after I do that,” she said, stressing that her long-term goal is to become an actress.

Her advice to other kids going through cancer treatment?

“What I try to do is stay positive. Be strong and just know that you can get through it … just have a positive mindset with what you’re going through, even though it’s really tough.

“Think about what you can do in the future.”