Cheating Death

by Sanjay Gupta

  We can’t say for sure. By now, many other patients at Duke and other academic cancer centers like UCLA and M. D. Anderson Cancer Center in Houston have received the same experimental treatments as Bailey did, as well as a few newer therapies. There’s been a measure of success—in some studies of monoclonal antibody treatment, average survival nearly doubled to almost two years—but almost no one makes it a dozen years, certainly not without a hint of trouble. 18 So what is it about David Bailey? Is he just a statistical quirk? Does he have good luck? Did God choose to save his life? Or is there something about his story that just might help other patients?

  THE PRESTON ROBERT Tisch Brain Tumor Center is a place where they try to put the puzzle together. Dr. Darrell Bigner, the director, is a soft-spoken man with a courtly southern drawl. In a storied scientific career, he has laid the groundwork for a number of cutting-edge treatments, including monoclonal antibodies, an approach that his lab first developed. Yet despite some advances against brain cancer, Bigner says bluntly that the disease is winning the battle. “It’s still a poor prognosis. There have only been two new treatments in the last thirty years, and to tell you the truth, neither of them is terribly effective,” says Bigner. “[On average] they might extend life, and quality of life, by just a few months.”

  According to the National Cancer Institute, the standard of care for glioblastoma is surgery, followed by radiation and Temodar. 19 That combination has been shown to increase average survival by about two months compared to radiation alone. 20 That’s not bad, but it isn’t great, either. We clearly need something better. That’s why Henry Friedman and the other doctors at Duke put so much emphasis on clinical trials. About two-thirds of the brain cancer patients who come through the door at Duke are put on an experimental protocol. 21 “Surgery, radiation, Temodar—we just don’t think that’s good enough. We don’t think that’s adequate,” says Friedman.

  If insurers will pay—and Friedman is aggressive in pushing them—almost every patient gets something extra: an experimental drug, procedure, or vaccine, for instance. The first extra tends to be Avastin, a monoclonal antibody that works to block the growth of blood vessels that feed tumors. After years of promising results from this experimental use, in May of 2009 the Food and Drug Administration officially approved Avastin as a treatment for GBM. (It had previously been approved to treat colon cancer). Other patients at Duke are funneled toward studies on monoclonal antibodies fused with radiation—the treatment Bailey got—or to anticancer vaccines.

  A Duke vaccine trial that’s received a lot of attention lately involves a substance called CDX-110. In the 1990s, a number of cancer researchers—Darrell Bigner among them—noticed something unusual happening with the proteins on the cell surfaces of glioblastomas, as well as on breast, ovarian, prostate, and colorectal cancers. The protein that made them take notice is known as epidermal growth factor receptor, or EGFR. In healthy cells, it binds to another protein, epidermal growth factor (EGF), part of a process that’s vital to the controlled division of cells.

  The researchers noticed that there was a lot more EGFR on the surfaces of tumor cells than there was on the healthy cells. What’s more, cancerous cells often display a mutation of EGFR, a version with a name right out of a Star Trek episode: EGFRvIII, or EGFR factor three. According to Dr. John Sampson, a cancer specialist at Duke, if EGFR is a switch controlling cell division, EGFRvIII is a switch that’s “on” all the time—constantly signaling the tumor cells to divide. 22

  Identifying this protein meant that cancer specialists had a target. Scientists from several major centers, including Duke, Stanford, Johns Hopkins, and M. D. Anderson all played a big role. They took a portion of the EGFRvIII protein and combined it with other substances that send the body’s immune system into overdrive. When injected, the vaccine triggers the body’s immune system to attack any cell that’s loaded with the mutant version of EGFR—in other words, the tumor cells. It’s like a heat-seeking missile. In an initial study where patients got CDX-110 along with Temodar and radiation, the vaccine more than doubled survival time. The average patient lived more than two years, instead of just a year. 23

  At Duke, the difference is palpable. Patients used to go home for a few months and die—now they come in with complaints like broken bones from skiing accidents. Says Sampson, “We see people back now that are having complaints and problems that you just don’t see in people with brain tumors. Like a guy four years out [from his diagnosis], who should have been dead three years ago—he’s out skiing, and hurt his knee.”

  Imagine hearing stories like this when you’ve just been given six months to live. They mean hope. Sampson says, “You can’t give people hope, unless you can show people someone who’s done well. It’s like jumping out an airplane without a parachute. You can be as optimistic as you want on the way down—it doesn’t change the outcome. But it’s different if you can point to a second rip cord.”

  Now, the CDX-110 vaccine is being tested in a larger study, at twenty cancer centers around the country. As high as hopes have risen, we need to remind ourselves that the therapy is largely unproven. But CDX-110 is part of a larger trend toward personalized treatments for cancer. Because it targets the mutant EGFRvIII protein, it only works against cancers that express the protein—about 40 percent of all glioblastomas, according to Sampson. At Duke, genetic screening is now the norm. At Duke and other centers taking part in the current trial, tissue from every malignant glioma is tested to see if it contains EGFRvIII. If it does, these patients get an EGFR inhibitor as part of their treatment. This is complicated stuff and full of uncertainty, but this is how miracles are made and how their mysteries are unraveled as well.

  As the patient, you want to try everything; you don’t want to leave any stone unturned. As the doctor, you know you have to weigh potential benefits against the risks, since side effects can literally be deadly. But most researchers—though of course many are doctors, too—have a different mind-set, and this brings up another problem. They’re trying to zero in on the right treatment—to solve the puzzle—and if you throw the kitchen sink at a patient, you can’t isolate what works and what doesn’t.

  To be clear, most major cancer centers do offer multiple treatments for patients. But the holy grail of cancer treatment is a way to predict which approach will help which patient. Here, genetic screening may help. Of more than twenty thousand genes that lay the foundation of our bodies, researchers have already identified about twenty that seem to be related to the incidence of brain tumors. With that information, they’ve identified a few specific genes that seem to signal whether a particular treatment will work in the first place before the treatment is ever given. Temodar, for example, only seems to help about 30 percent of glioblastoma patients, those who carry one particular gene. 24

  Even as a surgeon, I can tell you that the future of treatment will lie outside the operating room. Remember, this is still a disease with no cure. I think the future for David Bailey and countless others around the world does involve personalized medicine, keeping in mind that glioblastoma is different in various groups of patients. It is true that all these tumors look the same when you’re staring down at them in the operating room, but when you look under a microscope and break them down on a molecular or genetic level, it’s different. One day we’ll have more examples like Temodar—we’ll know that if you have x gene, you’ll respond to y treatment. I also suspect that, someday, genetic profiling will explain those extremely rare cases, like Chuck Burrows or Alice Epstein, whose bodies are able to somehow reject cancer on their own. It will be further proof of something we have known all along, that every patient is different—and that every tumor is different as well.

  FOR DAVID BAILEY, a diagnosis of deadly cancer was a new beginning—not the end. About six months into his recovery, his hair still gone from radiation therapy, Bailey was sitting in his Virginia living room, waiting to see if the monoclonal antibodies would keep the cancer at bay. By then he’d got
ten to wondering about what he should do with his life, whatever was left of it. The job in Massachusetts was gone. Between the headaches, surging emotions and memory problems, selling software again seemed unthinkable. As he sat on his couch, sunk in thought, Bailey’s wife placed a guitar in his hands. He had plucked away during high school and college but hadn’t touched the instrument in years.

  “I started crying,” he remembers. “I had lost some vision, and I didn’t even know if my fingers worked. But I started going, started playing again that same day. It just unlocked a whole bunch of things.” He started practicing and writing songs. With each passing week, he gained strength in his hands. With each MRI that came back clean, he gained confidence, and before long, he was performing in local coffee shops. In two years, he had his first CD—of more than twenty. 25

  Along the way, he’s played in forty-four states and Europe, in every sort of venue, but he says he finds the gigs for cancer groups especially meaningful. “I step back and remember,” says Bailey. “For a lot of people in the audience, me just stepping on stage and saying, ‘Twelve years [since his diagnosis]’ is the victory.”

  He told me, “I remember in those first weeks [after the diagnosis], I went for this long walk, and on this walk I did what I assume a lot of people do. I got pissed off at God, waved my fist at the sky, and I cursed, ‘Why me?! Why me?!’ And I tell that story, and the audience always understands. These days, I imagine God saying, ‘Wrong question. Don’t ask ‘why?’ Ask, ‘What now?’ It’s a huge epiphany. But it adds a huge responsibility. You realize you’re not the total victim you maybe thought you were.”

  Here’s how he put it in a new song “Fragile.”

  Lookin’ in from the outside

  Don’t know what to say

  Storms will come every day

  But even hurricanes go away

  You just learn what it takes to be strong

  Don’t have to be fragile very long

  To beat stupendous odds, to make a miraculous recovery, you need a few crucial ingredients. You need a patient with the inner strength not to give up and the wherewithal to seek help. And you need a doctor who is willing to try almost anything. You need hope—the kind of hope that Henry Friedman offers. The kind of hope that guides him in making a million tiny decisions, medical calls, and trial and error that add up to lifesaving treatment.

  “The motto is so simple,” says Bailey. “ ‘At Duke there is Hope.’ But it’s amazing: so many people miss the boat about how important that is. For us, there is no such thing as false hope. There’s hope, and there’s no hope. I weave this into my concerts, telling people, you’ve got a choice: dig in your heels, wrap yourself around hope, or crawl into a corner and die. There’s nothing in between.”

  DARRELL BIGNER BROUGHT up something I had wondered about when I first learned of David Bailey’s story. Until the 1990s, he told me, pretty much every long-term glioblastoma survivor was probably a case of misdiagnosis: some other, less aggressive tumor. In Bailey’s case, that’s not the issue. Multiple brain scans and biopsies at a top-notch cancer center left no doubt that he had a deadly glioblastoma. At the time he was first diagnosed, there was no one, literally no one, who could say they’d survived the illness for more than a decade. And yet in 2008, we found him alive and well, just like the title of his latest CD.

  Bigner says there are more stories like this one to come. “We don’t want patients to think this is a hopeless situation. Unfortunately, unless you are actively trying to cheat death, this is what we’re told by the vast majority of the medical profession. Our patients hear it all the time: ‘You’ve got this malignant brain tumor; there’s nothing to be done but palliative care. Go write your will, take a nice vacation and get ready to die.’ And that’s not really the case at all.”

  When Henry Friedman criticizes other doctors for giving up on their patients, he uses the same words as Stephan Mayer and Lance Becker: “therapeutic nihilism.” That’s the notion that nothing can be done. For some terminal patients, that’s true. But even with an illness as deadly as glioblastoma, there’s hope if you’re willing to take a fresh look. “The status quo is unacceptable,” says Friedman. “If we use the same interventions we’ve always used in the past, there’s no reason to think the outcomes will be any different, but if we are hopeful and use interventions that are new… .” his voice trails off for a moment. “Well, then the canvas is totally unpainted.”

  It certainly echoes the stories we’ve heard about other patients left for dead. Back in 1996, when David Bailey was diagnosed with brain cancer, a skier like Anna Bagenholm, who was trapped under freezing water for two hours, probably never would have made it to a hospital. A cardiac arrest victim like Zeyad Barazanji—who had stopped breathing for five minutes—might have been left to languish in a coma. Not to mention Mark Ragucci, whose doctors said was doomed to life as a vegetable, if he lived at all. Like other doctors we’ve met in these pages—Stephan Mayer, Gordon Ewy, Mads Gilbert—Friedman isn’t waiting until he has all the answers. He works with what he has, pushing his patients—and colleagues—to try something new. The more they try, the more patients who decide to fight, the more David Baileys we’re likely to see.

  MATT PFENNINGER’S STORY is a little different. Pineal germinoma—Matt’s brain tumor—is not invariably fatal. Overall, the survival rate is around 60 percent, according to the American Cancer Society. Still, to beat cancer is almost always a long and winding path, and that brings us back to the Pfenninger home in Midland.

  You see, just six months after the deeply moving prayer service and Matthew’s miraculous recovery—well, that’s when the story really begins. The tumors came back. In fact they recurred in two places on either side of his brain. The locations were so delicate that surgery to remove either tumor was out of the question. “That was the beginning of the worst part,” Matt told me.

  At that point, the Pfenningers, like so many others before them, made their way to Durham, to the Preston Robert Tisch Brain Tumor Center and Dr. Henry Friedman. Under the care of Friedman and a pediatric oncologist, Dr. Joanne Kurtzberg, Matt underwent a series of bone marrow transplants. His condition improved enough for him to fulfill a lifelong dream by attending the University of Michigan in Ann Arbor. But it wasn’t meant to be. A few weeks into his freshman year, he dropped out. Matt told me, “I could barely eat anything. There was a hole starting to form in the roof of my mouth as a side effect of all the medications. It was not fun. It’s supposed to be the best time of your life, and I couldn’t have been more miserable.”

  What Matt went through the next two years is frankly too horrible to imagine for most people, but he recounted it for me with astonishing detail. There was surgery to remove a tumor that had spread to his lung. An artery and a vein became fused, which led to another surgery, taking out a third of the lung. Another day, sitting down to a meal of tacos at home with his father, Matt felt liquid in the back of his throat. Standing over the sink, he coughed up two liters of blood. He made it to the hospital, choking blood into a salad bowl while his father drove. He passed out in the waiting room. “I felt like I was going to die,” he told me. “It was pretty peaceful. I was sad for the people I was leaving behind, but I wasn’t scared at all.” The nurses desperately packed his nose full of cotton to stop the bleeding.

  From there it was back to Duke, for another bone marrow transplant. On this go-round, Matt jokes that the only doctor he didn’t see was the gynecologist. The family ran up $2 million in medical bills, as Matt got daily blood transfusions for three months. He had a throat full of tumors, with constant blood clots that threatened to cut off his breathing. One day he passed out from loss of blood and had an emergency tracheotomy. He ended up on a respirator. He couldn’t eat; five months into his hospital stay, he had a tube in his gallbladder and a feeding tube in his stomach. The first time medical staff put in the feeding tube, it wasn’t tightened properly and it leaked, so he ended up with a severe infection inside his abdo
men. He could no longer go to the restroom on his own.

  Throughout the seven-month hospital stay, Matt’s mother, grandmother, and sisters took turns by his bedside, while his father kept up the home in Midland. More than once, Jack Pfenninger got a call from Duke, telling him to get down there, that his son might not make it through the night. At that point, says Matt, “I was just waiting to die. I was ready to go. The doctors kept telling me it was going to be okay, but I was pretty convinced it was over.”

  One especially painful day, Pfenninger leaned across his son’s bedrail and whispered the most difficult words he’d ever spoken: “If you want to let go, just let go. I won’t hold you. I’m not going to make you suffer.” After hugging his son, Jack had his hand on the door to leave, when Matt managed to speak, saying, “Dad, I love you. And I want to come home.” Jack took it as a stubborn promise.

  No one knows what makes for a turning point in a long illness like the one that almost killed Matt Pfenninger. But right around the day of that promise, his condition took a turn for the better. Maybe that’s as much of a miracle as the time his tumors went away after the round of group prayer. In any case, the next MRI showed the tumors in his brain were stable. The next thing he knew, they were shrinking. Less than two months after his dad’s visit, Matt staggered off a plane in Midland, looking up at a skywriter’s message: “Welcome Home, Matt.” It was Father’s Day 1997.