Lawyer, entrepreneur and avid athlete Mark Clements participated in the 2005 St. George Marathon in Utah, but ongoing stomach pains made finishing the event a struggle.
“He was having some stomach pain,” recalled his sister Stacie Lindsey. “My dad had had ulcers, and so he thought that he had ulcers.”
After finishing the marathon, Clements, then 38, went straight in to see his doctor. Ultrasound and other tests confirmed that it wasn't ulcers -- Clements had cholangiocarcinoma, or cancer of the bile duct.
“They could clearly see that it had metastasized outside the liver,” Lindsey said. “It had spread quite prolifically.”
Bile duct cancer is a relatively rare cancer, with an estimated 8,000 to 20,000 new cases diagnosed each year, said Lindsey, who is CEO of the Cholangiocarcinoma Foundation.
Unfortunately, only a small number of bile duct cancers are found at an early, treatable stage, according to the American Cancer Society. That's because the bile ducts are located deep within the body, making small tumors virtually undetectable during routine physical exams. Right now, there are no screening tests that can identify bile duct cancers, Lindsey noted.
All of this means that the overall five-year survival rate for bile duct cancers is just 9% for those starting within the liver and 11% for those starting outside the liver, the ACS says.
“The average is about a one-year survival,” Lindsey said.
Clements died in January 2007, 15 months after his diagnosis.
There is some reason for hope, however: Thanks to the work of researchers, physicians and groups like the Cholangiocarcinoma Foundation, advances in potential new screening tools and treatments are occurring.
“There's a lot of hopeful, hopeful news here because we have more clinical trials available, more FDA approvals, new standards of care coming,” Lindsey explained. “This is really a very exciting and hopeful time for this community, whereas in the past, there were no options available. This is really an exploding area of science and research.”
The worst news
Days after he ran the marathon, Clements called his family together and told them that he'd been diagnosed with an inoperable, incurable cancer.
The pronouncement kicked off months of intense research and networking by Clements' family, as they searched for some way to save him, Lindsey said.
The bile ducts are a series of thin tubes that run from the liver to the small intestine. They deliver bile from the liver and gallbladder, which is used to help digest fats as they pass through the intestines.
Clements' late-stage diagnosis is far from unusual, said Dr. Arif Kamal, chief patient officer for the American Cancer Society (ACS).
“It's typically found pretty late when people are symptomatic, either through pain in the right part of the abdomen or, more often, jaundice,” Kamal said.
Cancer blocks the bile ducts, causing the greenish-yellowish liquid to back up into the bloodstream, Kamal said. When that happens, it causes people's skin and the whites of their eyes to take on a yellow hue.
“Because of the bile salts being deposited into the skin, it can also cause itching,” Kamal added. “Those symptoms are how we know there's something going on, and it's generally spread by the time those symptoms occur.”
Lindsey scoured the internet for information about bile duct cancer. The family created an online discussion board about the disease, which allowed them connect with other families and researchers.
At the time, Clements' only treatment option was chemotherapy, Lindsey said.
“There were no clinical trials available for him,” she said. “There was no standard of care at the time.”
It was her brother's illness that led to the creation of the Cholangiocarcinoma Foundation.
“As we were traveling home, he and I, from one of his last doctor's appointments, he asked me what I was going to do with all the information and connections that we'd made along the way,” Lindsey said. “I told him I didn't know, and he said, well, there will be a lot of people who will be diagnosed with this cancer who will not have the kind of support that he had. And he said, you know, we need to help them. I think we need to start a foundation.”
A couple of weeks after that conversation, the family filed the nonprofit paperwork that led to the founding of the Cholangiocarcinoma Foundation. The foundation supports research, raises awareness, and helps patients and families.
Hope on the horizon
Within the past three years, a number of advances have taken place regarding treatment of bile duct cancer, Lindsey said.
Since 2010, the standard of care for cholangiocarcinoma had been a combination of the chemo drugs gemcitabine and cisplatin, Lindsey said.
But last year, the field got a new standard of care, in which those chemo drugs are now combined with the immunotherapy drug durvalumab (Imfinzi), Lindsey said.
“It had long been thought that cholangiocarcinoma was a 'cold' tumor, meaning that it doesn't respond to immunotherapy treatments, so we're really grateful to have had that approval,” Lindsey said. “That opens up a lot of new options for patients.”
Newer targeted drug therapies also are available, the ACS says.
Drugs like pemigatinib (Pemazyre), infigratinib (Truseltiq), and futibatinib (Lytgobi) target fibroblast growth factor receptors (FGFR2) that cause bile duct cells to grow out of control and turn cancerous, according to the ACS.
Many more treatments are being investigated, Kamal and Lindsey noted.
“Right now, there are hundreds of clinical trials open to cholangiocarcinoma patients,” Lindsey said.
Researchers have also made some headway into figuring out the risk factors for bile duct cancer, so that better screening for the cancer can occur.
Age has typically been the leading risk factor for cholangiocarcinoma, with most people diagnosed in their 60s or 70s, Kamal said.
However, certain diseases of the liver or bile ducts are also known to increase risk, most prominently a condition called primary sclerosing cholangitis (PSC). In PSC, inflammation of the bile ducts leads to the formation of scar tissue.
Catching it early
“We have one promising project that we are supporting that is an early test for PSC patients,” Lindsey said. “About 20% of PSC patients turn into cholangiocarcinoma patients.”
Researchers also are investigating a blood test that could look for minute genetic traces of bile duct cancer in a person's bloodstream, also known as circulating tumor DNA, Lindsey said.
Other gastrointestinal diseases like inflammatory bowel disease also can increase risk of bile duct cancer, as well as exposure to certain toxins, Lindsey said. People who are obese or who have type 2 diabetes also have increased risk.
Genetics are yet another risk factor for bile duct cancer receiving more attention, Kamal said.
“For the average person, we don't screen for cholangiocarcinoma,” Kamal said. “But if we knew that there was a family history of it, then that might change our approach. We might do some CT scans, for example, to look if we saw someone had a remarkable family history.”
The problem is that people often don't know the exact type of cancer that a family member had, and that information is crucial when it comes to upper GI cancers, Kamal said.
“Oftentimes people say grandma had liver cancer, and what they mean is that she had a cancer in the right side of the abdomen, kind of near the liver, and we're going to call it liver cancer,” Kamal said.
Liver cancer isn't generally considered a cancer driven by genetics, Kamal said. Other factors like hepatitis or heavy drinking typically drive liver cancers.
“Cholangeo would be a different thing. If you knew that grandma had bile duct cancer and then this aunt had bile duct cancer, then that might change what we do for that person who's the grandkid of this grandparent,” Kamal explained.
“But if someone says grandma had liver cancer and the aunt had stomach cancer and both of them are actually bile duct cancer, then you miss the trend that's happening," he noted. "You miss it because you're wrong essentially on the specificity of the cancer type.”
Kamal agrees with Lindsey that progress is being made.
“I would say overall there's more excitement than ever before about new types of treatments,” Kamal said. ”But we're still at the early phases of understanding. There is optimism those things are coming. It just can take a little bit longer.”
The Cholangiocarcinoma Foundation has more for newly diagnosed bile duct cancer patients.
SOURCES: Stacie Lindsey, CEO, Cholangiocarcinoma Foundation; Arif Kamal, MD, chief patient officer, American Cancer Society.