Around 2016, Mary Witkop noticed a lump on the inside of her right knee. Concerned, she consulted several doctors and all agreed that the mass was probably harmless.
“I probably saw five or six doctors who all told me it was a lipoma, which looks like fatty tissue,” Witkop, 64, of Beulah, Michigan, told TODAY. com. “A doctor told me that if it bothered me, appearance-wise, she would send me to a surgeon.”
After meeting with a surgeon in the summer of 2018, Witkop decided to delay his removal. When she returned to meet with the surgeon months later, he noticed that the lump had changed and sent Witkop for scans of the mass. In February 2019, Witkop learned why the lump had grown so large in a short period of time: it was an aggressive type of soft tissue cancer.
“He had just been misdiagnosed because no one had done any imaging,” Witkop says. “They were just diagnosing me based on my appearance.”
Knee bump leads to diagnosis
When Witkop visited the surgeon in 2018, he told her she would have to keep her knee dry for two weeks if she had surgery. That meant Witkop and her husband had to skip days on the nearby river during the hot summer months. So she chose to wait and returned to the doctor at the end of 2018.
“He told me it was a little different,” she said. “He wanted me to do some tests.”
That surgeon sent him for an X-ray and then an MRI, and in February 2019, he was diagnosed with stage 3 undifferentiated pleomorphic sarcoma, an aggressive type of soft tissue cancer, according to the National Library of Medicine.
“I was very lucky that I didn’t have surgery in the summer of 2018, because he didn’t know he had sarcoma and probably wouldn’t have removed it properly,” says Witkop. “There’s a good chance my sarcoma has spread.”
Sarcomas are rare, according to the American Cancer Society, which estimates that 13,590 people will be diagnosed with them in 2024. They are so rare that Witkop has had difficulty finding a doctor to treat them.
“I couldn’t see any local doctors or hospitals to treat the sarcoma,” she says.
Witkop traveled four hours to the University of Michigan in Ann Arbor to meet with doctors. His treatment plan included five days of radiation therapy for five weeks, then surgery to remove the mass. Doctors asked her if she would be interested in participating in a clinical trial to determine whether the immunotherapy pembrolizumab, also known as Keytruda, could improve outcomes for people with sarcoma.
“I was still in shock. I was just told I have cancer,” she said. “I didn’t understand what they were saying.”
After the shock wore off, Witkop thought about what participating in the clinical trial might mean for others and agreed to participate.
“I thought, ‘Well, I hope this helps me, but if it doesn’t help me, it might help someone else,'” she explains. As part of the clinical trial, Witkop received an infusion of the drug before starting radiation therapy and then another afterward. After recovering from the radiation, she underwent surgery and received an immunotherapy infusion after surgery.
“They took a piece off the left side of my knee,” she said. “They were about the size of a grapefruit that they took out and then they had to take my calf muscle and put it in the hole to fill that gap. And then they took a skin graft from my thigh to cover the muscle.
Afterward, the surgeon revealed that she didn’t get as clean a margin as she would have liked because it was too close to Witkop’s bone. Doctors consider a margin to be clean if there is no evidence of cancer around the edges of the tissue, indicating that everything has been removed. To recover all the tissue, the surgeon would have to amputate Witkop’s leg, but his surgeon decided not to do it. But that increased Witkop’s chances of the cancer coming back.
“The risk of recurrence was twice as high if you didn’t get a (clean) margin,” Witkop says. “I started crying, sobbing on the spot.
Doctors considered adding more radiation to reduce the risk of recurrence, but Witkop had a bad reaction and couldn’t take any more. Although she felt nervous about the cancer returning, Witkop was optimistic that participating in the clinical trial would be enough.
“I had a lot of hope,” she says. “I really believed that if there was still cancer there and it was going to come back, this Keytruda was going to save me.”
Recovery after surgery was difficult. After an 11-day hospital stay, Witkop went to inpatient rehabilitation closer to home for about three weeks so she could learn to walk again.
“It was extremely painful,” she said. “The nurses told me it was one of the most painful surgeries.”
Sarcomas, a rare class of cancers
Sarcomas are “cancers that occur in muscle, fat, blood vessels and other connective tissues,” said Dr. David Kirsch, head of the radiation therapy program at the Princess Margaret Cancer Center at the University Health Network in Toronto, who did not treat Witkop. tells TODAY.com.
Sarcomas may occur more often in people with genetic mutations that predispose them to cancer, such as Li-Fraumeni syndrome, an inherited condition that makes people more likely to develop cancer, Kirsch says. Patients who have previously undergone radiation therapy for other cancers have a higher risk of developing sarcoma, he adds.
“The majority of sarcomas do not result from prior exposure to cancer treatment or genetic predisposition,” he says. Like other cancers, they develop spontaneously.
Signs of sarcoma can include a fast-growing, painless mass, “greater than five centimeters” located deep in the body, Kirsch says. But it can be difficult to detect masses, especially if people don’t have other symptoms.
“These are difficult tumors to diagnose,” says Kirsch. “They can be very difficult to treat because they are so rare.”
The Sarcoma Trial
“(Sarcomas) account for about 1 percent of all adult cancers and 15 percent of pediatric or young adult cancers,” says Kirsch, who led the Stand Up 2 Cancer Catalyst research team, which studied the use of immunotherapy in the treatment of sarcomas.
Their rarity and complexity (there are more than 100 different types of sarcomas) make them difficult to study, he notes.
“This makes it difficult to make progress in treating sarcomas, because we don’t have the numbers of patients that we have for more common cancers,” Kirsch says.
This means that sarcoma treatment has not advanced in the past 25 years. Treatment usually includes surgery and radiation, he says. However, Kirsch and colleagues decided to look at an existing immunotherapy treatment, pembrolizumab or Keytruda, which the same Witkop underwent.
They looked at two of the most common adult sarcomas: undifferentiated pleomorphic sarcoma and dedifferentiated pleomorphic liposarcoma. He says a previous study showed that people with metastatic forms of these cancers had a response to pembrolizumab, and investigators hoped that by introducing it earlier, patients would benefit.
“We thought that if we moved (with immunotherapy) earlier in the course of the disease, before the cancer spread, that might improve outcomes,” he explains.
The team recruited 127 patients from the United States, Canada, Italy and Australia into one of two groups. One group received radiation therapy and surgery and the second group received pembrolizumab in addition to traditional treatments. People in the second group received immunotherapy infusions before, during and after radiation therapy and after surgery.
Researchers found that people who received immunotherapy along with standard treatment were 43% less likely to experience a relapse two years after treatment. The researchers recently presented their results at the American Society of Clinical Oncology.
“Our hypothesis was that if we added the immunotherapy, pembrolizumab, both before surgery, while we are giving radiotherapy and also after surgery, it would reduce the risk of the cancer coming back after two years,” says Kirsch. “That’s exactly what we saw.”
This discovery means that some sarcoma patients have new treatment options.
“This is a real breakthrough and a step forward for patients with these rare tumors,” he says. “This is an example of how we can make progress in these types of (rare) diseases.”
“These studies are simply incredible”
Since completing treatment, Witkop has been cancer-free. She was able to return to work as an attorney with the Little River Band of Ottawa Indians in Manistee County, Michigan, where she provides legal advice and assistance to tribal members. Her husband and family are members of the tribe.
“It’s a fabulous job,” she says. “I can help people without charging them a fee. It’s just a wonderful feeling.
While his physical health has improved, Witkop struggles with depression after his cancer experience.
“I don’t think I managed my emotions enough,” she says. “I took an antidepressant which helped immensely.”
She hopes her story will encourage others to consider participating in clinical trials.
“If people are offered a clinical study (I hope), they agree to participate because it gives them hope,” she says. “Even if it doesn’t help this particular person, it might help someone in the future.”
As for his participation in the research, Witkop has no regrets.
“I truly believe that this study…saved my life since my doctor was not able to get (clear) margins,” Witkop says. “These studies are simply incredible.”