New treatment strategy aims to stop rare liver cancer
Jerry Widawski knew the statistics were not in his favor. At 68, he was diagnosed with a rare and difficult-to-treat cancer called intrahepatic cholangiocarcinoma, which was destroying his liver.
“I don’t know what percentage of people survive what I have; probably not a lot,” Widawski says. “They gave me less than a year.”
Because of the rarity of the disease, “we didn’t really have a prescribed treatment,” says his wife, Susan.
The course they chose to take led them to OHSU Knight Cancer Institute, where a surgeon specializing in the treatment of advanced liver tumors came up with a complex and demanding plan. This would require a series of operations over several months, including the surgical implantation of a device to infuse chemotherapy drugs directly into the liver, called a hepatic arterial infusion. No one could predict the chances of success.
“I don’t even know if I can voice my concerns because I was worried about everything,” Susan said.
Today, more than two years after his last chemotherapy infusion, Widawski is cancer free. And his surgical oncologist, Skye Mayo, MD, MPH, is leading a clinical trial at OHSU to determine if the treatment strategy can be scaled up to save the lives of more people with cholangiocarcinoma.
“I think we have a lot to learn from Dr. Widawski,” says Mayo, an associate professor of surgery at OHSU’s School of Medicine.
Cholangiocarcinoma of the liver is diagnosed in approximately 5,000 people each year in the United States – and the incidence is increasing. Surgery to remove these cancers is rarely curative, especially if it has spread to the liver. The cancers come back in 60 to 70 percent of cases within five years, Mayo says, and surgery is only feasible in about 10 to 20 percent of people with liver cholangiocarcinoma.
In Widawski’s case, surgery seemed out of the question. The cancer had taken too much space in his liver. “It’s kind of surreal when you get that kind of diagnosis,” Widawski says. He had been active and in excellent health, playing volleyball competitively for many years and practicing law in Astoria. His only symptoms had been weight loss and fatigue.
After the diagnosis, “I prepared for the worst,” he says. “It was going to be what it was going to be. I am pragmatic. I don’t worry about things I can’t control.
Working with OHSU’s hepatic arterial perfusion team, Mayo’s multi-step plan was to first shrink the tumor with high-dose chemotherapy. This required the surgical implantation of an automated pump to infuse anti-cancer drugs directly into the liver via the hepatic artery. This allows exposing the cancer to doses 400 times greater than if the drugs were given intravenously into the general circulation and exposing non-target organs, Mayo says.
Widawski spent a year with the pump implanted delivering chemotherapy drugs to his liver at a fixed rate, overseen by a team that included an OHSU oncologist. Adel Kardosh, MD, Ph.D., gastrointestinal cancer specialist. For several months, drugs delivered by hepatic arterial infusion caused the tumor to shrink enough to allow an attempt to surgically remove the cancer.
But first, Mayo had to stimulate the growth of healthy liver tissue to support the work of the parts of the organ that would need to be removed along with the tumor. Mayo accomplished this with a procedure called portal vein embolization, which blocked blood flow to all cancerous segments of the liver.
“The cancer-free side of the liver will grow big enough that you can remove all of the large portion of the cancer-containing liver and not go into liver failure,” Mayo says.
It took only four weeks after the embolization procedure for the clear fraction of the liver to expand sufficiently. Two weeks later, Widawski underwent surgery to remove the cancerous segments of the liver, leaving behind a healthy, cancer-free liver. The amount of cancer remaining in the removed sections was minimal, but the dense scarring, called fibrosis, was extensive. All of her lymph nodes tested negative for cancer. “So an incredible response,” Mayo says.
Inspired by the results, Mayo developed and initiated a Phase 2 clinical trial (the HELIX-ICC study), enrolling people with liver cholangiocarcinoma that was considered inoperable. Selection criteria exclude people with cancers that have spread beyond the liver and those previously treated with radiation therapy, among other exclusions.
“We want to be sure, before exposing you to an intensive sequence of treatment, that we are really doing it for the right reasons,” says Mayo. “We want to be sure that we have done everything we can to identify patients who have disease outside of the liver or who will not benefit from it.”
The study digs much deeper than a typical clinical trial, with co-investigators from many disciplines gleaning insights. Collaborating scientists are studying multiple aspects of tumor response to treatment, including gene activity and interactions with the immune system. The complex trial was launched at the height of the COVID-19 pandemic.
“We allow the patient and the research team to come together to adapt and see, based on all the evidence, what we should do for your cancer,” Mayo says. “And it’s not the same treatment for everyone. Once patients have completed the clinical trial protocol, we tailor and personalize the approach to the specific aspects of their unique cancer.
Patients’ quality of life is assessed at baseline, at four points during treatment, and at an additional two points after the end of the six-month treatment protocol. This unique quality of life research is conducted by Lissi Hansen, Ph.D., RN, professor at the OHSU School of Nursing.
“So many people, when they are diagnosed with this disease, feel like they have six to nine months to live,” Mayo says. “After surviving more than six to nine months, what is your life like now? What does survival mean? That’s what Dr. Hansen’s quality of life research really highlights for our patients in the trial.
Susan Widawski says one of her biggest concerns was that the demanding treatment might hurt more than it helped. “Since it’s unclear what the outcome might be, I think I was more worried that he would go through all the treatment and not have a good quality of life,” she says. “It hasn’t been an easy ride, but that wasn’t Jerry’s mindset. I think he believed that if he could help advance a new science or he could help other people, he would move forward.
Her husband says the hardest part was some of the aftereffects of the repeated surgeries. “I lost a lot of weight. I can’t get it back. Other than that, I’m fine,” he says. “Persistence is what I learned. I didn’t have much luck. For me, it’s the doctors – they’re the ones who gave me a chance to make this thing work for me.
Widawski continues to practice law, although he says he is heading into semi-retirement. The couple recently bought an RV and are planning some summer adventures.
“The future, he says, looks bright.