When the cramps suddenly started to grip him, Laurent Tessier thought he had swallowed too much ice cream. “But my stomach was swelling, swelling, swelling more and more every day,” says the adolescent from Baie-d’Urfé.
“On Friday I was a normal 9 year old boy. On Sunday, I couldn’t go skating. X-rays showed that a liver tumor was crushing all of my organs. ”
For two and a half years, there would not be much “normal” for Laurent. Especially not his Christmases – lived two years in a row in a hospital room at CHU Sainte-Justine.
The first time, the doctors had transplanted a new liver to her. The second, her chemotherapy treatments were causing unrelenting pain that even morphine was not enough to alleviate.
“He was in too much pain to stay with us for an hour for supper. We had to bring him back to Sainte-Justine, ”recalls his mother, Hélène Tessier.
From 9 to 12 years old, Laurent went through a procession of hardships that grips the heart. Seven surgeries. Several stays in intensive care. Severe internal bleeding. Dozens of chemotherapy treatments …
The big boy with the black eyes therefore suffered the worst. But if he speaks to us five years later, it is because he survived it. Because Laurent is the first and one of the most brilliant successes of a genomic investigation program (of all genes), launched to offer young people personalized treatments – more targeted and effective.
In its infancy at CHU Sainte-Justine, in 2012, the pediatric oncology precision medicine research program (called TRICEPS) was unique in the world, says molecular geneticist Daniel Sinnett, who co-directs it.
TRICEPS now covers all of Quebec and was copied across Canada in 2017.
Without genomic profiling, about 20% of children and adolescents with cancer die. “We are talking about young people at the end of the course, for whom we have tried everything,” says Daniel Sinnett.
In Quebec, 40 children lost their lives each year.
Examining all their genes – to identify anomalies – now allows about one in three to escape, revealing at the last minute unsuspected treatment options.
PHOTO FROM THE CIUSSS DU NORD-DE-L’ÎLE-DE-MONTRÉAL SITE
Daniel Sinnett, molecular geneticist, co-director of the TRICEPS program
When we found a molecule for Laurent, he only had a few weeks to live. We saved several like him, by discovering a therapeutic option that we did not even know before.
Daniel Sinnett, molecular geneticist, co-director of the TRICEPS program
Solve a mystery
Like typos – which can distort the meaning of words in text – genetic abnormalities cause the body to not receive the right instructions. This is often the reason why a patient does not respond to treatment as expected.
Each individual has specific alterations; billions of combinations are possible. Currently, dozens of molecules can correct certain mutations in children. Others will eventually be discovered.
Laurent suffered from liver cancer. But it was a brain cancer drug that ultimately saved him. “Pills targeted exactly his mutation, but since no liver cancer had been treated like that in the world, the oncologist had to develop a recipe,” explains Professor Sinnett.
“In nine months, all the metastases were gone! rejoices the geneticist. Laurent was starting to play hockey and soccer again and he was spending Halloween. ”
In other cases, genomic profiling instead reveals that the patient’s cancer was not the one believed to be or was more serious.
15 years ago, reading a patient’s genome was not an option. The exercise, called sequencing, still cost a fortune and took an insane amount of time.
Thanks to blazingly fast high-speed sequencers, this can be done in 24 hours today, for around $ 1,500.
Caregivers are increasingly relying on information obtained in this way, says Daniel Sinnett. “At first, our reports were Chinese to them, so they were more cautious. Now they decide to take action more often. ”
Laurent Tessier discovered with fascination the Sainte-Justine genomics laboratory: “I love science! I would like to become an engineer or an inventor because I want to do a lot of things. ”
For example, he envies the team that designed the puncture-proof tires for the Rover mobile robot, sent to Mars. “I love challenges, rack my brains”, sums up the teenager.
Racking his brains out is exactly what Daniel Sinnett and his colleagues did to save his life … and make him a little bit puncture-proof, too.
Available to all children
All children and adolescents in Quebec now have their genome analyzed as soon as they are diagnosed with cancer – without waiting for a possible failure of traditional treatments or a relapse.
Around 180 patients have benefited from this major innovation since the SIGNATURE research program was launched in November 2019.
Derived from the TRICEPS program, it made it possible to discover personalized treatments (or to refine the diagnosis) of two young people out of three – that is to say 118 of them. “They will be less damaged by the treatment if they receive the right treatments at the start”, rejoices the geneticist in charge of the program, Daniel Sinnett.
Chemotherapy, for example, attacked the kidneys of Laurent Tessier. “If he had been diagnosed today, he could have gotten the right medication on day 1 instead of going through three or four unnecessary rounds of chemotherapy. ”
“However, it is much easier to try an unconventional treatment when a patient relapses and has nothing left in front of him – as was the case with Laurent – than to do it at the start”, observes the researcher.
To choose targeted therapy from the start, he says, caregivers have to completely change the way they think.
“If it takes too long, we have lost the patient”
Seven weeks. This is the time required to discover an unexplored treatment in extremis – or to refine a diagnosis – when a young person is on the verge of death from cancer. Here are the four stages of this race against time.
1. Obtain patient agreement
The patient or his parents must consent to the genetic investigation. “Even if we can’t find anything, it at least makes their mourning easier,” says molecular geneticist Daniel Sinnett. They know that we have tried everything by analyzing the three billion letters of the genome and looking at all the drugs available around the world. ”
Result Almost 99% of the 291 patients (or families) approached from April 14, 2014 to September 15, 2021 agreed to have the investigation carried out.
2. Collect and analyze cells
To obtain the complete genetic portrait of a patient, we must operate or do a biopsy to remove bone marrow or tissue, then analyze everything. This sometimes turns out to be impossible, which almost happened to Laurent. “His lung metastases were very difficult to reach,” explains Daniel Sinnett. We had to scratch the material because we had very little of it. We worked with fine lace. ”
Result A sample could be analyzed successfully in 83% of the young people.
3. Find “actionable” mutations
The biological material is fed into a device called a high-throughput sequencer, which analyzes DNA and its three billion letters in record time. Bioinformaticians use powerful computers to identify all the “typos” in the genome. These abnormalities can be counted in the thousands in each patient. “After eliminating all those for which there is no treatment, we end up with two to five actionable mutations,” says Daniel Sinnett.
Result Genetic mutations opening up new therapeutic avenues were identified in 84% of young people whose cells could be analyzed.
4. Present the results at the weekly clinical oncology meeting.
Experts in molecular profiling present their findings to caregivers at the four pediatric oncology centers in Quebec. They analyze this new information together. About one in three times they convince them that the patient’s therapy needs to be changed quickly. “It is the attending physician who has the last word, because he knows whether the patient is able to tolerate the treatment or not,” underlines Professor Sinnett.
Results
In a third of cases, the doctor prefers to keep the alternative approach as plan B, if the patient’s condition worsens further. In other cases, this avenue must be abandoned because it is already too late for the patient or the medication he would need remains inaccessible.
In numbers
1/400
One in 400 children learns they have cancer before the age of 14
80%
Survival rate of children with cancer in the West since the mid-1990s, compared to 15% in the 1960s