• Research

    Discovery’s Edge: Slay the Dragon

Thomas Hoffman of Spearfish, S.D., was 56, weighed 235, and had been diagnosed with prediabetes when he began to diet. As the pounds melted away, his wife became alarmed at his rapid weight loss. Then one morning, he awoke and his wife told him he was completely yellow — not from the sun streaming into the bedroom, but from jaundice. So Hoffman reported to the emergency room at the Veterans Administration medical center in Sturgis, S.D.

“Doctor comes in and gives us the news: ‘You have pancreatic cancer. You’ve got six months to live. Get your stuff together,’” says Hoffman. “What do you do?”

What his doctors did, in fact, was to send Hoffman to Mayo Clinic, where he met Mark Truty, M.D., a surgical oncologist, who is rewriting the protocol for treating pancreatic cancer with notable success. Dr. Truty started Hoffman on chemotherapy right away, followed by radiation, and a difficult 10-hour surgery. Then came more chemo.

Mayo patient Thomas Hoffman is two years down the road from his pancreatic cancer diagnosis, cancer free, and riding Harleys again.
Mayo patient Thomas Hoffman is two years down the road from his pancreatic cancer diagnosis, cancer free, and riding Harleys again.

Now, nearly two years after his diagnosis and more than a year after his surgery, Hoffman remains by all indications cancer free. Despite a painful recovery from the surgery itself and difficulty with his digestion, “I’ve gained my strength back where I can ride my Harley again,” Hoffman says. “I’m never going to be 100 percent. But hey, I’ll live with whatever it frikkin’ takes. I just want to be as normal as I can. I can do my little hobbies. I can help my son out. I can see my grandkids. I help my wife in her business. I just do what I do."

A diagnosis of pancreatic cancer has long been viewed as a death sentence. That’s true of the public, and doctors as well. “There’s a real stigma attached to this disease,” says Dr. Truty. “Once you get that label, it’s basically over, given the historically poor outcomes.”

In 2015, about 50,000 patients in the United States were diagnosed with cancer of the pancreas, according to the National Cancer Institute. It ranks as about the 10th most common cancer, but the fourth most deadly. Only 6 percent will live more than five years after diagnosis.

But Dr. Truty has pioneered a radical new protocol for treatment of the disease, starting with therapy using new cancer drugs and following with marathon surgeries that are rarely tried in conventional treatment.

Says Dr. Truty, “We’re trying to change the mentality — we have new drugs and now we’re trying to attach those new drugs to more aggressive operations that doctors have previously denied patients.”

Mayo surgeon and researcher Mark Truty, M.D., is determined to offer both options and hope to patients with pancreatic cancer.
Mayo surgeon and researcher Mark Truty, M.D., is determined to offer both options and hope to patients with pancreatic cancer.

Data on 50 of Dr. Truty’s patients show remarkable success, especially among patients who, by conventional criteria, would have been deemed inoperable.

“People get that diagnosis and they hide. They look on the Internet or they’re aware of the disease, and they don’t tell anyone, because there’s such a bad association with it,” says Dr. Truty. “I want people to talk about it — ‘Yes, I have pancreas cancer. What are my options?’ They’re significantly better now than they were even five years ago.”

Deadly Spread

Pancreatic cancer is deadly because it spreads long before any symptoms appear. And except for a few families, pancreatic cancer appears random, so there’s no good way to predict who will get it or know who to screen.

For decades pancreatic cancer patients have been treated with the same order of treatment and with dismal results. A surgeon sliced out the tumor. Chemotherapy then followed surgery if the patient was able to recover from the operation well enough to tolerate chemotherapy. If the tumor was inoperable, the patient received chemo alone.

But that approach fails in several ways. First, an operation alone for pancreatic cancer is of minimal benefit. All patients with pancreatic cancer need chemotherapy. Chemotherapy drugs have, until recently, been largely ineffective.

Second, surgery does no good if the tumor has already metastasized. Or if cancer cells at the margin of the excised tumor remain behind and later spread. “Those patients derive zero benefit from the operation,” says Dr. Truty. “Basically for the last 30 years we’ve had the same practice across the country, across the planet, and we’ve had basically no incremental improvement in outcome.”

Dr. Truty was particularly interested in the 35 percent of pancreatic cancer patients who show no signs of metastasis though, in fact, their cancer may have spread undetected.
But they aren’t considered for surgery because their tumor has entwined too many veins, arteries, and other tissues. They are usually given chemo and a poor prognosis. Median survival is less than a year.

“I thought, boy, if we could even get half of them through our chemotherapy-radiation regimen and somehow treat them surgically, we’d basically be doubling the number of patients that we could potentially treat,” says Dr. Truty. He has a personal interest in trying to improve outcomes.

“My father had pancreas cancer,” Dr. Truty says. “He went through the traditional approach. He went to the operating room, had major complications, never got chemotherapy, and died in my arms six months later. I see that same thing occur 25 years later, over and over and over. We keep doing the same thing and hope for a different result.” Because his father had pancreatic cancer, Dr. Truty himself has an elevated risk. “So I have a vested interest in this as well.”

New Protocol and Difficult Surgeries

The first step to improving cancer treatment, Dr. Truty decided, was switching to more effective chemotherapy drugs. He settled primarily on FOLFIRINOX, a multi-drug potion shown in a New England Journal of Medicine study in 2011 to be far more effective than older drugs.

Second, Dr. Truty decided to prescribe his patients chemo- therapy right away rather than as a follow-up to surgery. That way, the drugs would have a chance to shrink the tumor and hunt down cancer cells that had spread far away from the pancreas. Moreover, the four months or so of chemotherapy allowed his patients to get in better shape. “We put them through physical therapy, meet with the nutritionist, the dietitians,” he says. “We get their symptoms under control, and then we actually go into the operation in significantly better shape to tolerate that procedure, both physically and psychologically.”

The imagery of St. George slaying the dragon adorns the facade of the Plummer Building on Mayo Clinic’s Rochester, Minnesota campus.
The imagery of St. George slaying the dragon adorns the facade of the Plummer Building on Mayo Clinic’s Rochester, Minnesota campus.

Dr. Truty decided to follow chemotherapy with radiation treatment, primarily to kill cancer cells at the site of the operation. If there’s still no sign the cancer has spread, and the patient’s strength holds out, Dr. Truty performs surgery, including extensive procedures that few other doctors would attempt. “Basically half of my practice are patients who have been deemed unresectable after being seen elsewhere. These are patients that have been told they have no hope. We’re now doing vascular resections, both of the veins that supply and drain the intestines and liver, as well tumors involving critical arteries, which has always been sort of a taboo.”

Dr. Truty’s prep begins the night before, reviewing the impending operation with other surgeons who will be involved looking at models printed from CT scans on 3D printers. The result is a nearly exact replica of the patient’s organs and tumor. “It’s challenging because every tumor is in a different location. Each tumor involves different blood vessels. There’s no textbook for how to do these operations,” says Dr. Truty.

The surgeries are marathon sessions, lasting up to 14 hours. “I’m willing to work an hour to move one millimeter in my dissection because I know this patient is going to do better than average,” he says.

As the hours wear on, Dr. Truty sends tumor samples to a pathologist who quick-freezes the tissue, slices it, and examines it for cancer — a technique developed at Mayo. “They go through it slice by slice, and they look into the microscope and they tell us how much tumor is still alive,” says Dr. Truty. “The pathologist will stay till 2 in the morning with me. The greatest excitement for me is when the pathologist says there’s hardly any tumor left.”

After surgery, Dr. Truty finishes with an additional round of chemotherapy. Each component of the therapy has a specific purpose. The result is a program that appears to be providing a genuine opportunity to actually cure pancreatic cancer. Says Dr. Truty, “We try to give them hope.”

Two years ago, Richard Hanson of Lakeville, Minn., felt what seemed like a gas bubble in his lower abdomen. “It just wouldn’t go away,” Hanson says. He visited his doctor, got a CT scan and MRI, and within a week received a diagnosis of pancreatic cancer. His doctor called Mayo Clinic and a day later Hanson met with Dr. Truty.

Hanson underwent the regimen of chemo, radiation, and surgery. As he was about enter the operating room, Hanson recalls Dr. Truty telling him, “Listen, I told you three to five years, but when I do surgery now it’s for the cure.”

Dr. Truty removed part of Hanson’s pancreas, 15 lymph nodes, and the spleen. “It was major surgery,” says Hanson. “He cut me open big.”

Hanson underwent a final round of chemo. More than two years after his diagnosis, he is showing no signs of recurrence. In fact, he has been golfing for the last year. “I finally got out onto the golf course and started swinging a club and that was really good therapy.”

Potentially Cured

Hanson is one of 50 patients Dr. Truty has treated over four years who make up a cohort for a study he plans to publish soon. All had stage III pancreatic cancer with such large entwined tumors they would have been considered inoperable. All were treated with FOLFIRINOX, radiation, surgery, and more FOLFIRINOX. Thirty-one required venous reconstructions to remove the tumor; 18 had arterial reconstructions. Four, like Hanson, required the removal of additional organs. Despite the severity of the surgery, all but three survived for a month beyond the surgery — in line with the national average for less invasive pancreatic cancer surgeries.

With conventional treatment, median survival would be expected to be less than a year. With this group, says Dr. Truty, median survival is 41 months and growing as patients continue to survive. Thirty-one of the patients so far show no signs of cancer. Dr. Truty anticipates that perhaps 40 percent will be alive five years after treatment. “Those are patients that are potentially cured, which is a word that we seldom use with these patients,” he says.

Yet greater gains are possible, Dr. Truty says. The first step is finding even better drugs for chemotherapy. To do that, says Dr. Truty, “we need better scientific models that represent the actual patient.”

In his other role as a researcher, Dr. Truty is growing tumors from human pancreatic cancer tissues in lab mice with weakened immune systems — so-called patient-derived xenografts or avatars. These tumors are derived from the very patients he operates on. Because the tumors are virtually indistinguishable from the tumors in the original patients, they provide ideal targets for drug testing. The mice also provide a way to identify protein “biomarkers” produced by the cancer tumors. The markers may someday be used to screen patients for cancer.

Growing tumors in mice also predicts the recurrence of cancer in humans. Cancerous tissue taken from a particular patient — after the regimen of chemo, radiation, and surgery — is transplanted into a mouse to determine if the cancer cells were killed or are likely to return. If the cancer cells grow in the mouse, that’s an ominous sign in terms of the aggressiveness of that particular cancer. On the other hand, says Dr. Truty, “This also gives us at least a four-and-a-half-month lead time to intervene when the tumor is still microscopic.”

Mayo Clinic is uniquely situated to support Dr. Truty’s brand of aggressive treatment and tumor research. First, a lot of patients come through Mayo, including a lot with pancreatic cancer. That provides an opportunity to develop and refine effective treatment. It also provides many variations of tumors for research.

Second, Mayo’s structure allows easy collaboration between researchers, oncologists, surgeons, pathologists — even veterinarians who maintain laboratory animal facilities. “People aren’t working independently,” says Dr. Truty. “It’s a whole team approach. That’s how this institution has originated.”

In Dr. Truty’s office hangs a print of St. George slaying the dragon. One can imagine that the writhing dragon looks a lot like a pancreas. Yet as much as cancer, Dr. Truty is also trying to slay pessimism. He hopes that someday soon, pancreatic cancer will be treated as a chronic disease, and not a death sentence.

“I don’t care what you’ve been told elsewhere. Come here and get another opinion,” he says. “Because we have made significant improvements. We have data that people are living significantly longer.”

-Greg Breining

March 9, 2016