It started with scattered reports of a mysterious symptom afflicting cancer survivors, with some of them in severe pain.
“We kept hearing about people waking up in the middle of the night with charley horses beyond anything you can imagine,” said Dr. Karen Syrjala, co-director of the Fred Hutchinson Cancer Research Center Survivorship Program.
“People would say ‘the pain is so bad that if I want to get somewhere, the only thing I can do is crawl across the floor.’”
Dr. Karen Syrjala
Only about 16 percent of the patients were obese based on their height-to-weight ratio. But a majority were obese according to the ratio of their body fat to lean tissue.
“For some reason, they were exchanging a lot of their muscle mass for fat cells,” Syrjala said.
Syrjala’s team is now in the fourth year of an ambitious project to unravel the mechanisms behind this problem. The ultimate goal is to develop treatments that could alleviate survivors’ musculoskeletal issues and potentially apply to a range of other ailments that have impacts on muscle such as diabetes and heart problems.
The research places Syrjala at the cutting edge of an unsung, but increasingly important, effort to improve cancer survivors’ quality of life. There are now roughly 14 million cancer survivors in the United States alone, up from about seven million in 1990, and a little more than 2 million when President Nixon declared a war on cancer in 1971. By 2020, the number of survivors in the U.S. is expected to reach 20 million.
Syrjala marvels at these numbers and the progress they represent. “When I started in this field, only 50 percent of cancer patients would survive five years or longer,” she says. “Now we’ve increased that to two-thirds.”
She’s also quick to point out that, while each survivor is a success story, treatment doesn’t stop when a patient is declared cancer-free. Cancer and its treatment have clear long-term effects, both psychological and physiological. Survivors can suffer from early osteoporosis, premature menopause, sexual dysfunction, anxiety, cancer recurrence and a host of other health issues.
The story of Syrjala’s effort to understand one of these problems illustrates the opportunity to help millions of survivors lead healthier, happier lives. It also encapsulates the challenges that come with working in a complex new field.
“Scientists like to follow a thread, not have a ball of yarn and try to disentangle it,” she said with a laugh. “But I guess we were stuck with the ball of yarn.”
Dr. Julia Rowland has spent the past 11 years as director of the National Cancer Institute’s Office of Cancer Survivorship, a position that’s given her a unique opportunity to watch survivor-related research evolve.
This evolution was sparked not by the medical community, but by a loose network of cancer survivors who worked to draw attention to their unique problems. The creation of the survivorship office legitimized their concerns and demonstrated a rising awareness that doctors’ obligations extend beyond
“If you’re going to cure someone of this disease, you want to be sure they have a life worth living,” Rowland said. Over the past decade, researchers have mainly focused on chronicling survivors’ health problems. According to Rowland, this made a critical contribution to survivorship research by detailing which maladies survivors face and how those maladies manifest themselves.
“We’ve done a good job mapping out the terrain,” Rowland said. “Now I’d love to see more attention going toward how we’re going to take care of the problems.”
The Hutchinson Center has been at the forefront in survivorship research. Since its inception, the Center has followed former bone marrow and stem cell transplant patients through its Long-Term Follow-Up Program.
“The Hutchinson Center has dedicated enormous resources for lifelong health surveillance of patients who are surviving after their treatment, some for more than 35 years,” said Dr. Paul Martin, the program’s director. “The welfare of our patients is very important. We have insight that other centers can’t match. Often, they look to us and learn from our data.”
The same kinds of contributions are coming from the much newer Survivorship Program, which seeks to improve the lives of cancer survivors. It’s within this context that Syrjala is conducting her research.
Syrjala is among a growing number of researchers pushing the survivorship field into new directions. But she acknowledges that it’s not easy. As her work shows, it takes years of painstaking—and expensive—research to get to the point where you can even start thinking about actual treatments.
Syrjala’s journey began with a difficult challenge: trying to systematically define survivors’ musculoskeletal symptoms.
Data on this issue was scant because survivors often didn’t report the problem to the doctors. The reason? Because musculoskeletal pain can be vague and complex and has many potential causes, survivors often don’t suspect it is related to cancer or its treatment.
“People will attribute [the symptoms] to anything from a cold to lack of sleep to the simple fact that they’re getting older,” Syrjala said.
Once researchers started asking survivors about these symptoms, they found that, whether it’s one year or 15 years after their treatment, many survivors report significant muscle aches and pains, muscle weakness, joint aches and pains, and cramps. In fact, fully two-thirds of bone marrow transplant recipients report some sort of musculoskeletal problem. Syrjala said similar rates are reported among breast cancer survivors.
The next challenge was identifying potential causes. A possible link came when Syrjala realized that the same type of chemotherapy used to treat breast cancer is used in the bone marrow transplant process. While it’s too early to say definitively that chemotherapy is what leads to the musculoskeletal problems, “we believe it’s at least one of the culprits,” Syrjala said.
Her team also found that in addition to experiencing muscle loss, the patients also have poor aerobic capacity. Imaging tests on survivors’ muscles suggested that these problems are probably related to dysfunction within the muscle cells.
Now, Syrjala and her colleagues are trying to isolate this dysfunction, which may lie in the cells’ mitochondria, or energy factories. To zero in on this, they have to take another difficult step: creating a lab model for testing.
Her team is working on the model now. Once these models mimic the musculoskeletal problems, the researchers can try to identify the biological and genomic changes behind these problems. Then they can start testing therapies that could reverse the musculoskeletal damage.
It’s a long road—Syrjala believes it will take another five years for her team to have concrete treatments in hand. The upside is that her work’s implications could extend far beyond musculoskeletal problems. Survivors vulnerable to musculoskeletal problems are also vulnerable to diabetes, cardiovascular disease and other maladies. Syrjala hopes research will reveal mechanisms that help unravel these other issues as well.
“What’s so exciting about this is that we think there’s a lot of overlap between these long-term problems after cancer treatment,” she said.
While Syrjala’s work could lead to important breakthroughs, it focuses on only one of the health problems survivors face. As a field, survivorship research “is still in the foundation-building phase,” she said.
With the number of survivors in the U.S. projected to reach 20 million by 2020, that research is going to become increasingly important. However, the NCI’s Rowland worries that a lack of funding poses a significant barrier to progress.
Rowland said it can be hard for survivorship issues to get attention from a philanthropic community that’s understandably focused on pursuing a cure.
“There’s always a dynamic tension between investing in a cure and investing in survivor care,” Rowland said, “and I don’t think that’s ever going to go away.”