When children and young adults are diagnosed with rare diseases, they and their families often aren’t sure where to turn for answers. The treatments that could be helpful might not come until years later, making a diagnosis in the here and now even more grim.
For years, patients diagnosed with fibrolamellar cancer faced a long road of searching — hoping the next treatment would be the one to save them. In 2017, Rush wasn’t treating any patients with this kind of cancer. Today, they are breaking ground on pioneering new treatments, giving patients and their families a newfound — and justified — sense of hope.
A rare liver cancer
Fibrolamellar carcinoma, or FLC, also called fibrolamellar hepatocellular carcinoma, is a rare kind of liver cancer that primarily affects adolescents and young adults (15 to 40 years old) who do not have underlying liver disease, as opposed to other kinds of liver cancer that are commonly associated with alcoholism, infection or hepatitis.
According to the National Cancer Institute, or NCI, there are so few cases of FLC that there isn’t enough data to know conclusively how many people have it. But it is estimated that there are about 50-200 new diagnoses in the U.S. every year. The NCI estimates that FLC makes up about 0.8% of all liver cancers, and the median age of a typical patient is 22.
Because it is such a rare form of cancer with few doctors having the experience to treat it, about 25% of patients will be diagnosed early with a stage 1 or 2 progression, according to Tom Stockwell, executive director of the FibroFighters Foundation, a leading nonprofit advocacy group.
Around 60% of patients have advanced disease with stage 3 or 4; the remaining 15% of patients are diagnosed with such an advanced stage of disease that they end up succumbing to the disease within three months to a year after diagnosis, without the opportunity for resection. Often, these patients are treated as having a variant of hepatocellular carcinoma.
“Because of its rarity, there is no definitive research or guidelines on FLC and it’s only been within the last 10 years that we’ve recognized FLC as its own form of cancer,” explains Paul Kent, MD, a pediatric oncologist at Rush. “Compounding the challenge is those who get FLC are adolescents and young adults, who typically are caught between pediatric and adult oncology programs and, consequently, may have disjointed care and worse outcomes.”
Innovative, multidisciplinary care
Martin Hertl, MD, PhD, MBA, the director of the Rush Solid Organ Transplant Program and division chief of transplant surgery at Rush, agrees that the age of the patients makes treating this form of cancer particularly difficult.
“If I have a teenage patient who needs surgery, they won’t typically see a primary liver surgeon,” says Hertl. “The oncologist who would treat them may be a pediatric oncologist, who sees very few liver tumors in children. They could be seen by an adult oncologist, who is used to treating elderly and frail patients with liver disease. This is what makes fibrolamellar cancer so challenging.”
Some institutions favor a transplant or surgery-only approach for FLC. Kent says that studies show patients relapse 85% of the time when using only surgery when the disease has metastasized beyond the original liver tumor, prompting the need for systemic therapy. At this time, although there are no proven systemic treatments, especially for patients with unresectable, relapsed, progressed or metastatic FLC, several new strategies being used at Rush show promise.
The foundation of Rush’s success in treating FLC lies within its multidisciplinary approach, involving surgery, oncology and interventional radiology, who all meet to discuss cases during the country’s only weekly FLC tumor board.
“Nowhere else in the world are these disciplines working together every week to treat FLC,” Hertl says. “This is what makes us unique.”
Five years ago, Rush wasn’t seeing any FLC patients. Now Rush is seeing the largest number of patients (55) in the country.
In one case, Rush became involved when a patient couldn’t be treated with a two-drug protocol (5FU and Interferon alpha-2b) at her existing institution. When the patient came to Rush, Kent worked with a provider at MD Anderson who developed the protocol to treating the patient.
“We (at Rush) thought the protocol was a great idea, backed by good science,” says Kent. “Initially, we were just offering what MD Anderson developed, but, over time, we’ve developed our own chemoimmunotherapeutic regimen (gemcitabine/oxaliplatin/lenvatinib or nivolumab/lenvatinib/quercetin). Each of those drugs had worked separately for other kinds of liver tumors, so it made sense to try and combine them.”
A favorite therapy of Kent’s — “Magic Mike” — was developed by a unique collaboration between Kent and one of his patients, "Mike," a scientist who had relapsed three times from FLC. They used a combination of nivolumab and lenvatinib, along with quercetin, an over-the-counter supplement, to successfully treat his disease.
“Here’s this scientist who’s written papers on parallel universes coming to me to try a therapy he envisioned,” says Kent. “It worked extremely well — all of his tumors disappeared. We tried the same therapy on our first patient, and almost all of her lung tumors vanished.”
Hertl notes, “Dr. Kent can offer therapies other institutions don’t because there are so few open clinical trials for FLC. You must treat the patient with what you feel is best practice. His therapies could become the standard of care in five or 10 years.”
Minimally invasive options
Equally as impressive as its oncological approach is Rush’s interventional radiology and surgical treatments for FLC. Patients fall into two categories:
- Those whose liver and lung tumors can be ablated immediately by freezing or heating them
- Patients whose tumors are too large for resection.
Jordan Tasse, MD, an interventional radiologist at Rush, can inject minimally invasive radiation particles into liver tumors to shrink them to surgical size.
“A lot of kids who we treat have already had major surgeries for liver resection and then they’ve recurred,” Tasse says. “If a patient doesn’t want another major operation, we can treat the tumor in a minimally invasive manner.”
Tasse also uses portal vein/double vein embolization, a cutting-edge technique used at Rush in greater volume than anywhere in North America. The liver and the skin are the only organs that can regenerate after portions of it are removed. If 70% to 80% of a patient’s liver is removed, for example, the liver will grow back to its original size.
For FLC patients whose livers are 95% diseased, cutting out that large a portion will cause the patient to lose liver function entirely. In cases like this, Tasse blocks the artery feeding into the lobes where the tumor is, cutting off its blood supply. In turn, that causes hypertrophy of the healthy part of the liver, quadrupling its size in about 10 days. Patients who initially didn’t have enough healthy liver tissue prior to surgery can undergo a resection to take out the cancerous growth.
“The outcomes with this procedure have been amazing,” Tasse says. “Generally, we see 30% growth of the future liver remnant in six weeks. With this newer technique, we’re seeing 50% to 60% in two weeks. This speeds up the time patients can get surgery and cuts down on the time the cancer can grow.”
An example of Rush’s multidisciplinary approach occurs during tumor ablation in the lungs. In combination with immunotherapy, the body recognizes the antigens from the ablated tumor, causing tumors elsewhere in the body that were not ablated to shrink — also known as the abscopal effect.
“The hope is that the immune system will recognize the tumor antigens once you ablate them,” Tasse explains. “It can be done in other parts of the body, but we’ve had success with the lungs.”
Path to a cure
With so few cases of FLC, collecting meaningful data is a major obstacle in finding a cure. Rush sends out FLC tumor samples to researchers at Harvard, Cornell, the Nagourney Cancer Institute and the Winthrop P. Rockefeller Cancer Institute — more than any other institution in the country.
“The only way we’re going to solve this problem is through more research and clinical trials,” Kent says. “In the meantime, we are doing our best to keep our patients alive and thriving until more is known.”
Through its innovation, dedication and thoughtful, committed approach, Rush is considered to be a world leader in FLC treatment. Rush treats patients from 29 states and six countries, getting patient referrals funneled through two main platforms — FibroFighters and the Fibrolamellar Cancer Foundation.
“More than half the patients who come to us are on hospice or palliative care — that’s common for us,” Kent says. “Some of those patients lived two years when they were told they had two months. Some have gone into remission. We’re giving options to patients who came to Rush without them.”