‘FREE FOR THE WORLD’
Pittsburgh pathologist prepares to launch a Wikipedia for cancer
In the early 1990s, Yuri E. Nikiforov was a young pathologist working in a hospital in Minsk, the capital of Belarus, when children began showing up at the doors with a rare and aggressive form of thyroid cancer.
The incidence of childhood thyroid cancer had been 1-in-2 million in the region, about the same as in Britain. By 1994, the rate had jumped to 1-in-10,000 — a 200-fold increase — as the number of children diagnosed with cancer eventually ballooned to 5,000.
Through research, Dr. Nikiforov, now vice chair of pathology at the University of Pittsburgh, helped connect the spike in childhood cancer in Belarus to the 1986 explosion and fire at the Chernobyl nuclear power plant 270 miles away. While some authorities were dismissing the idea as impossible, Dr. Nikiforov took the idea a step further, linking specific genetic mutations that led to the disease at a time when genetic medicine was still new.
He will need all that grit and more now in creating an international cancer registry, a medical education resource thathe wants to base in Pittsburgh.
The World Tumor Registry Inc., a nonprofit that will be free to doctors and patients, officially launches Monday at the annual convention of the United States and Canadian Academy of Pathology in Baltimore, where some 6,000 attendees are anticipated.
The purpose of the registry — a cancer Wikipedia — is to minimize diagnostic errors by giving doctors a searchable online database of cancers that have been collected and categorized with cellular images collected from around the world. Although there are many cancer registries, the World Tumor Registry will be unique in its ease of use and international breadth, supporters say.
Today, pathologists searching to identify a thyroid tumor flip through thick textbooks that are updated every three years or so, which are filled with
cancer cell photographs, mostly drawn from North American and European patients. Dr. Nikiforov’s online registry will be updated continuously with curated images of tumor cells, which can be greatly enlarged at a click of a mouse, that are collected and categorized from patients worldwide.
“Such people like Yuri make our world better, not only by generating ideas, but by bringing them to life,” said Alyaksandr Nikitski, research assistant professor at Pitt, who has worked with Dr. Nikiforov since 2016. “This is the cool thing about Dr. Nikiforov. The idea is to bring together all world knowledge.”
Dr. Nikiforov, 61, a gangling, all arms and legs 6-foot-2 man, arrived in the U.S. in 1993 with physician wife Marina, 62, and two small children. He soon went to work in a research lab at Cedars-Sinai Medical Center in Los Angeles under endocrinologist James A. Fagin, who became his mentor. Dr. Fagin has since become chief of medicine at Memorial Sloan Kettering Cancer Center in New York.
The cost of living was high in southern California, and Dr. Nikiforov’s pay was paltry; he remembers his wife knitting clothes for their children and bringing home a found TV because they couldn’t afford to buy one.
“On a training salary, I’m sure it was a struggle for him in Los Angeles,” Dr. Fagin said. “But once he’s on a path, he’s careful and rigorous. He believes in what he’s doing and puts all his soul into it. And that’s what it takes to be successful. I would do anything for Yuri.”
Medicine has a troubling history of slow catch-ups between research breakthroughs in the lab and changes in how doctors treat patients. Some studies indicate that it can be 17 years before a new evidence-based intervention makes its way into clinical practice.
Dr. Nikiforov knows the resistance well.
A more accurate test
In 2000, he began thinking about a new, more accurate genetic test for thyroid cancer. Some colleagues laughedat the idea, he said.
Why bother, they said. Only about 2,100 people in the U.S. die each year from thyroid cancer and the five-year survival rate after diagnosis and treatment is very high — 98%.
“Take a piece of the thyroid — who cares,” he remembers doctors saying. Surgical complications are rare.
But ease of surgery wasn’t the only thing to think about, Dr. Nikiforov said.
A 2013 study of 200,000 people with cancer found that having thyroid cancer carried a higher risk of bankruptcy than lung, uterine, leukemia, colorectal, breast and other cancers. Worse, the youngest age groups were up to 10 times more likely to face bankruptcy than older age groups, probably owing to higher debt-to-income ratios in the younger group, according to the study.
In 2007, Marina Nikiforova, wife of Dr. Nikiforov and director of the Molecular Anatomic Pathology Laboratory at UPMC, developed the first ever molecular thyroid cancer test for use by doctors who treat patients. They called the test ThyroSeq.
ThyroSeq was a seven-gene panel at first, but improvements soon followed: a 13-gene panel version of the test was released in 2013, then a 56-gene panel was launched in 2014 and finally a version that analyzes 112 genes and identifies more than 12,000 mutation hotspots was marketed by 2019.
Between 20% and 40% of test results for cancer of the thyroid, a butterfly-shaped organ at the front of the throat, could not confirm a malignancy. Patients were often left anxious, or worse, choosing diagnostic surgery and with its unnecessary risks.
Research has shown ThyroSeq’s accuracy rate in finding cancer is 97%.
Over 100,000 ThyroSeq tests have been administered since 2007, making it the second most popular test doctors use in diagnosing thyroid cancer, according to marketing data.
Another challenge awaited Dr. Nikiforov in 2016 when he began urging the World Health Organization to accept research that he’d coordinated among two dozen pathologists from seven countries. Their findings concluded that something then classified by WHO as thyroid cancer was actually not cancer at all.
Worldwide, some 45,000 people were diagnosed annually with the tumor that WHO eventually reclassified as noncancerous in 2017. It had routinely been treated with surgical removal of the thyroid and a radioactive isotope, things Dr. Nikiforov and his colleagues said were unnecessary.
Pitt’s Dr. Nikitski is not surprised by the resistance his colleague has faced in this career. Academic medicine can be a tough place, he said, and challenges are routine.
“You cannot avoid it,” Dr. Nikitski said. “Any progress in our world is met with some fight. Anything new is always met with skepticism. Only after many years, people admit, yes, he was right.”
Dr. Nikiforov thinks he is right about the value of the new tumor registry, an educational resource that he describes as “from the world, but free for the world.”
A grateful couple
The difficult early years at the lab in Los Angeles are far behind the Pitt research pathology couple, who Dr. Nikiforov says wake up every day grateful for the opportunities the U.S. has afforded them. Dr. Nikiforov is now recognized as an international thyroid cancer expert and by the end of the year, the new World Tumor Registry is expected to be open with an exhaustive collection of annotated thyroid tumors while organizers continue to solicit funds for ongoing operations.
If all goes as planned, breast, prostate, lung and other cancers will be added to Dr. Nikiforov’s cancer registry by 2027.
Dr. Nikiforov dismisses the idea of monetizing the registry, of turning it into a for-profit venture.
“Money has never been a driving force for me,” Dr. Nikiforov said. “We’ve always been driven by other things. More money doesn’t give more happiness.
“I want to do something to change medicine,” he said.