John Illis, 77, spent most of his life in Detroit, working on the railroad and raising a family. Then he and his wife retired to the little town of Mesquite, Nevada, a high desert oasis with a cluster of casinos and golf courses. Near both the Arizona and the Utah borders and about 80 miles north of Las Vegas, the town didn’t even have a hospital when Illis arrived. The local, 25-bed community hospital opened just 10 years ago.
That didn’t seem like too big a problem until Illis received a diagnosis of bladder cancer. Even though he traveled 40 miles for treatment at a larger facility, Intermountain Healthcare in St. George, Utah, the cancer soon spread to his lungs. Before long, it seemed as if Illis was out of options. His favorite hobbies, golf and hunting, became poignant memories.
Then his doctor at Intermountain, Lincoln Nadauld, suggested that he get his cancer genome sequenced. Nadauld, who is also a consulting assistant professor at Stanford University, explained how it would work: They’d take a sample of Illis’ tumor, analyze the tumor’s DNA, and based on what genetic changes they found in the tumor, see if his cancer might respond to specific drugs targeted at those genetic changes. A group of doctors, both at Intermountain and at larger institutions like Stanford and the University of Oklahoma, would discuss Illis’ case and decide what to do.
The genomic analysis revealed that Illis’ tumor had an alteration in a particular gene known as FGFR3. The chemotherapy pill Votrient (pazopanib), which targets this gene, had already been developed. After taking the pill, Illis had a dramatic response: His tumor shrank for six months and then remained stable for another 10 months. Illis worked his way back to exercising at the gym three times a week. He has recently switched to another targeted pill, Iclusig (ponatinib) and is waiting for scans to see how his cancer responds.
“It’s really remarkable for patients in such a small community to have access to this,” Nadauld says. “Without this, the cancer would have taken Mr. Illis’ life a long time ago.”
It’s really remarkable for patients in such a small community to have access to this. Without this, the cancer would have taken Mr. Illis’ life a long time ago.
“Everyone doesn’t have the chance to have this targeted therapy,” Illis says. “For most people, it’s [traditional chemotherapy] or nothing.”
The Research Disconnect
As we enter the early days of truly personalized medicine, a huge gap in patient care still exists: Big research hospitals are sketching out the genomic profiles of different diseases and devising targeted therapies to address the genetic alterations that underlie those diseases. Some dramatic progress has been made, especially in cancer treatment. But most patients don’t receive their care at bustling academic centers. Nearly 85 percent of cancer patients are treated at small community hospitals, places that focus on patient care, not research.
“It’s a three-part problem,” explains Mark Watson, chief operating officer of the Guardian Research Network, based in Spartanburg, South Carolina. “First, community hospitals don’t have clinical trials to offer. Second, patients don’t have access to cutting-edge treatment. Third, researchers have lots of trouble finding patients.”
Around the country, several healthcare systems and research groups are trying to bridge these gaps. However, the genomic sequencing technology that makes these efforts cost-effective is just a couple of years old. Genomic collaborations between research hospitals and community hospitals are so new that few academic papers have been written about them.
“The last two years have been transformational in genetic testing and in our understanding of cancer,” says Heather Hampel, a professor of medicine at Ohio State University. “The challenge is to get that transformational medicine to patients.”
Bringing Genomic Medicine Home
For instance, John Illis may have been in a small town in Nevada, but his tumor genome was analyzed and discussed by cancer genetics experts not only at Intermountain, his home hospital, but also at Stanford University, the University of Oklahoma, and several other institutions.
“At Intermountain, we decided that we needed to make genomic cancer medicine and the expertise of big cancer centers more broadly available,” explains Nadauld. “There are only opportunities to improve when we collaborate like this. We’re at a confluence: We have the technology and the treatments to deliver better outcomes.”
Each week, doctors from Intermountain, Stanford, and the University of Oklahoma participate in a videoconference. This “molecular tumor board” discusses tumor alterations and possible treatments. Doctors from 10 other institutions participate as-needed. Sometimes, doctors from half a dozen states or countries may come together in this way. During the conference, each doctor can share patient data that’s been de-identified for privacy reasons.
These collaborators now offer this testing and tumor-board analysis to any outside institution in the United States. They have been working together for only a year and already they have a stack of success stories.
“We had a colon cancer patient whose cancer had metastasized to his liver,” Nadauld says. “He was 49 years old. He had five children. And he had [no treatments] left. We found that he had an alteration in his HER2 gene. Only 3 percent of colon cancer patients have this alteration, and it’s so new that we weren’t even sure what it means.”
Nadauld presented the case to the online tumor board and found that his colleagues were enthusiastic about trying HER2 drugs, usually reserved for breast cancer patients, on the colon cancer patient. His tumor shrank from 8 centimeters to just 1 centimeter. He got off pain meds. He went back to work. He got to see one child graduate and another child get married. He died about 18 months after starting the targeted treatment.
“The lay public is disappointed when they hear that a patient died. But to my mind, we bought a bunch of time for this person,” Nadauld says. “Even five years ago, it would have been a different outcome.”
Screening for the Masses
As genomic analysis transforms treatment, collaborations between researchers and clinicians are also beginning to change how people are screened for cancer.
Hampel is bringing genomic screening for colon cancer patients to 42 hospitals around the state. From 1995 to 2005, she conducted a study that showed that 1 in 35 patients have a mutation in one of several genes that lead to an increased risk of colorectal cancer. The condition is called Lynch syndrome.
Her study revealed that the Lynch syndrome mutations might be even more common than the BRCA1 and BRCA2 mutations linked to breast cancer (the reason for Angelina Jolie’s double mastectomy in 2013). Just as with the BRCA mutations, relatives of someone with Lynch syndrome have a dramatically higher probability of developing cancer. Hampel wanted to make screening for Lynch syndrome available at hospitals both big (like the Cleveland Clinic in Cleveland) and very small (like the Mercy Medical Center in Canton, Ohio).
“We’re offering free genetic testing and counseling to all relatives of patients who test positive. That’s where you save lives. Community hospitals just aren’t set up for this. They don’t have the labs. They don’t have the genetic counselors,” Hampel says. “It feels like it’s a health disparity. Why should you get better care because you are diagnosed at a big hospital? I understand that a [community hospital] can’t afford to have a geneticist on staff, but why can’t we work together? We’re taking away the barriers of cost and access.”
Hampel’s team has tested 1,400 colon cancer patients and their relatives since early 2013 and has found 70 patients who had Lynch syndrome or another hereditary cancer syndrome. She’s also starting a new arm of her study to extend even more genomic testing to screen those who test negative for Lynch syndrome for the next 25 most common cancers.
Hampel hopes her study will prove that genomic screening is worthwhile and perhaps be used as a model for statewide genomic testing centers across the country.
Going Really Big and Really Small
now that we know more about the genetic problems that cause disease, patients are being divided into smaller and smaller subsets. The benefit is that those patients can get targeted care, but these very specific kinds of patients may be scattered across states and hospital systems, researchers explain.
As genomic knowledge grows, the need for patient data will increase as diseases once thought to have a single cause turn out to be caused by many different genetic changes. But information sharing can’t happen unless research hospitals and community hospitals work together nationally, experts say.
The Guardian Research Network in Spartanburg hopes to create a framework in which groups of hospitals can collaborate to share genomic data and to improve both research and treatment. The network, which is still in its early launch phase, has already reached out to identify founding partners in 115 hospitals in four major community hospital systems.
“That represents about 100,000 patients as a starting point, and it’s heading toward one million patients,” says Watson, of the Guardian Research Network. The hospitals in the consortium will fund the network. Even though they will share data, each hospital will still be able to own its information, rather than donate it. The hope is that researchers interested in developing treatments targeting specific genetic variants can access the network and sift through the genomes of hundreds of thousands of people at both small clinics and huge university hospitals to find other patients whose tumors have similar genetic profiles.
“The goal is to enroll all the patients [with similar genetic variants] in a study at once. Researchers could open and close a clinical trial in half the time,” Watson explains. “We’re not developing a new technology. We’re deploying the technology in the most effective way. That’s the most important thing sometimes.”