The Cancer Chronicles Read online

  Instead of beaming rays from outside, oncologists might decide instead on brachytherapy: small capsules of radioactive isotopes inserted in or near a tumor. For some cancers, radioisotopes are injected into the bloodstream. Radioactive iodine, for example, will concentrate in the thyroid and attack malignancies there. A targeted drug called Alpharadin delivers radium directly to metastatic bone cancer cells. Whatever the method, the rationale is the same as with chemotherapy: Rapidly dividing cancer cells will succumb more quickly to the poison than healthy cells, and they will be less able to repair themselves.

  Both Nancy’s surgeon and oncologist agreed that her left and right groin, where the lymph nodes had bulged with carcinoma, should be treated with beta radiation. In the right groin, the cancer had encroached into the epidermal layers, and beams of electrons would impinge just deep enough to reach any cells that the chemo had missed. The doctors disagreed, however, on whether they should also irradiate her entire pelvis with x-rays. The surgeon thought the risks were unwarranted. Radiation can leave internal scars that cause bowel obstructions and it can hurt other organs. Damage to the lymphatic system can bring on lymphedema, an accumulation of lymphatic fluid that can cause chronic swelling of the torso and limbs. Very rarely the mutations induced by radiation will trigger another cancer decades later. There were so many trade-offs to consider.

  Certain that he had excised every bit of compromised tissue, the surgeon thought pelvic radiation would be dangerously redundant—that the weeks of chemo followed by superficial beta rays should be insurance enough against escaping metastases. Using more radiation now, when it might not be absolutely necessary, would limit the options if there was a recurrence later on. Both chemo and radiation destroy bone marrow, weakening the body’s ability to withstand further therapeutic assaults. “Save your bone marrow for future battles,” another doctor advised. Nancy’s oncologist was having none of this. He thought that hubris was clouding the surgeon’s judgment. So aggressive a cancer in so young and healthy a woman called for an extreme counterattack. Forgoing pelvic radiation, he told Nancy, would be gambling with her life. There was no right answer. The experts at MD Anderson also recommended whole pelvic and that is the course we chose.

  Firing rays at cancer cells sounds like a shotgun attack. But the planning and precision is impressive. Medical scanners—CT, MRI, PET—map the tumor and surrounding organs in three dimensions. In aiming the beam, pathways and angles are chosen that avoid the most vulnerable organs. Dosages are calculated meticulously—some organs are more sensitive to radiation than others and so are some tumors. Treatments are scheduled so smaller doses can be spread over days and weeks, gradually enough for the healthy cells to repair or replace themselves but not so gradually that the cancer regains the upper hand. Computer-guided robot arms can deliver graded doses to different parts of a tumor. To reduce the amount of radiation passing through healthy tissue, beams can be pointed from several directions, each weak in itself, converging to deliver the maximum jolt.

  For all the care and calculation, damage is unavoidable—the fatigue, the burning skin, the tingling nerves, the diarrhea. Radiation shines through the bowel, creating a sunburn inside. Bulky food worsens the condition, and Nancy was advised to follow a low-residue diet, avoiding high-fiber foods: whole grain breads, coarse-grained cereals, fresh fruits, raw vegetables, wild or brown rice. Also to be avoided were strongly flavored vegetables—broccoli, brussels sprouts, cauliflower—all these things that under other circumstances are supposed to be good for you. All these foods she loved. Chile and other spicy fare, popcorn—all were forbidden. She grew accustomed instead to the taste of Imodium.

  Looking back years later through the big ring binder where she kept the papers from this horrible time, I was struck by a couple of absurdities. Among the research papers weighing the dangers and advantages of pelvic radiation and the waivers acknowledging the near- and long-term side effects was a disclaimer: In preparing the patient for treatment ink marks might be made on the body. Nancy had to sign a release recognizing that the ink might rub off on her clothes. She was also advised to avoid getting pregnant.

  During the chemo sessions I could sit with her in the light-filled lounge with those beautiful mountain views. For the radiation she was taken into a lead-lined room. Alone with the robot deftly swinging its arm and zapping its preprogrammed targets, she felt like she was in sickbay on the Starship Enterprise. She would try to visualize the rays killing the cancer cells and sparing the rest. My strongest memory from that time is the day I drove her to her first treatment. As we approached, she fought back tears. She had been through so much already and I rarely saw her cry. “I can’t believe what they’re doing to my poor body,” she said. And, like so many times, I had to suppress the guilt. I told myself again that her cancer was not known to be estrogen related, that my not wanting to have children was unlikely to be the cause. But who could really know? And what about the stress I had caused her—the blasts of cortisol skewing insulin skewing the metabolic balance? Was there some slight chance—yet to be enshrined in the literature—that radon was a factor? I imagined the gas seeping into pores and orifices. It is part of the curse of being human: this idea that you get cancer because you did something wrong or someone—something—did it to you. For Nancy no cause was ever identified. The best that could be said was that she was a victim of randomness. But randomness can be complexity too deep to understand.

  It was during this time that we drove on a Saturday afternoon to the campus of the New Mexico School for the Deaf where the American Cancer Society was holding its Relay for Life. People with cancer are no longer called patients or victims but survivors, and they walked proudly around the track wearing blue T-shirts with a big star and the word “HOPE” in capital letters. (Nancy had another T-shirt at home that said “Not Dead Yet.”) I’ve saved five pictures from then. She is wearing black shorts or a midlength skirt—I can’t tell for certain—and I see that her right leg is already swollen with lymphedema. We were assured that it was probably a temporary side effect of the surgery—from damaged lymph vessels—and aggravated perhaps by the treatment. But the swelling never went away. It wasn’t such a bad compromise, she would say, for being alive.

  Her plan had been to rip off her hat during the procession, bearing her bald head in celebration of having endured the surgery, the chemo, and the first sessions of radiation. But the moment never seemed right. The most memorable part of the day came as the participants walked one by one to the stage, where they briefly introduced themselves, and the first lady of New Mexico bestowed them each with a gold medal and purple ribbon. “I am a cancer survivor,” the first woman said, and then the next and the next. I thought of how we’ve come to sugarcoat our afflictions. Deaf becomes “hard of hearing” becomes “hearing impaired”—and then loops back full circle with the embrace of Deaf Community and even Deaf Culture. Now there is a cancer culture, and whether you had a harmless in situ carcinoma removed with a simple lumpectomy or are fighting the terminal stages of metastatic melanoma, you are called a survivor. In the first case there was nothing to survive. In the second case there will be no survival. The word has been all but stripped of meaning. My thoughts were interrupted when a tall, thin woman with a chemo scarf grabbed the microphone and proclaimed: “I am a second-time cancer survivor.” Was that really something to celebrate? That the cancer had come back again.

  Chapter 12

  The Immortal Demon

  On the early morning flight from Albuquerque to Boston, the captain was wearing a pink tie, and a pink kerchief was peeking from the pocket of his uniform. The flight attendants were similarly dressed, with pink shirts and aprons. It was National Breast Can- cer Awareness Month, and when the plane was in the sky one of the attendants enthusiastically announced that the airline was selling pink lemonade and pink martinis—this on a flight departing at 6 a.m. The proceeds would go for “curing” breast cancer.

  No more than a hundred years ago cancer
was a word spoken only in whispers lest the illness be stirred from its slumber. One might die of “heart failure” or “cachexia,” a latinized way of saying that, eaten by cancer, a loved one had wasted away. Though the fear has not disappeared, “cancer” is no longer the unutterable word. The cheerfulness with which the subject has been embraced and shouted is almost macabre. A cosmetics company was advertising “Kisses for the Cure.” Buy a lipstick and a small donation would be made to the fight. “Pucker up and Kiss Breast Cancer Goodbye.”

  As I paged through the airline magazine, I thought of the Stand Up to Cancer telethon I’d watched a few weeks earlier, with singing, laughing, and sometimes somber celebrities vowing to “eradicate” cancer of all kinds. Not control it or reduce it or treat its occurrence more effectively. “Someday no child will die from cancer,” a buoyant teenaged actress promised. Not a single one. “We must beat it back and beat it out of existence,” said Stevie Wonder, hunched over a piano. His first wife had died from cancer, and many of the other stars had also been closely struck. “Cancer doesn’t care that you’ve won the Olympic gold medal. Cancer doesn’t care if you’re beautiful or brilliant or just starting college.…” One by one in their “Cancer Survivor” T-shirts, the idols and their idolizers took the stage. “Cancer doesn’t care if you have your whole life in front of you.…Cancer doesn’t care that you have young children who need their mother.…Cancer doesn’t care that it just took your father.…It just doesn’t care.” A ticker tape message scrolled across the bottom of the TV screen: “Cancer Doesn’t Discriminate.” But it does. Against the elderly, the obese, the poor. Demographically the young, beautiful people on the show were exceptions. But who could resist their good hearts and cheer? “The stars are taking your calls.” And so the telephones rang, the pledges poured in. At the end of the show a procession of scientists filed across the stage to a rousing chorus of “You’ve got to stand up, stand up, stand up to cancer.…” Altogether more than $80 million was raised that night.

  Stand Up to Cancer is a respected organization reputed to funnel almost all of the money it collects to research. But I wondered if the viewers, as well as the performers, had been left with false hopes. The donations, it was said, would go to “dream teams” of scientists cooperating on a cure instead of competing for recognition and grant money—as if only greed and egos stood in the way of understanding the most complex of medical phenomena. Comparisons were made to Jonas Salk and the March of Dimes, yet polio had been a vastly simpler problem—a disease with a single cause that could be isolated and vaccinated against.

  Understanding cancer will require no less than understanding the deepest workings of the human cell. One performer invoked the fight against slavery and the triumphs of the civil rights movement. “What if no one stood up for freedom on the Underground Railroad … if no one was standing up for injustice at a bridge in Selma?” Cancer was something to demonstrate against or to oppose with a sit-down strike. These didn’t seem like people who were apt to engage in mass acts of civil disobedience like those of ACT UP, the AIDS Coalition to Unleash Power, whose influence lay in its obnoxiousness. Two decades ago, ACT UP demonstrated against the National Institutes of Health and shut down the Food and Drug Administration for a day, demanding more research money and affordable treatments. One way or another more attention became focused on the problem. Now AIDS can be managed as a chronic disease. But not even HIV is as convoluted as cancer.

  Descending toward Boston, the plane provided a bird’s-eye view of what vies with MD Anderson as the most powerful cancer center in the world. On one side of the river were Dana-Farber, Beth Israel Deaconess, and Massachusetts General Hospital. On the other side were the Whitehead Institute, the Broad Institute, and the campuses of Harvard and MIT. With their petri dishes, gas chromatographs, gene sequencers, and electron microscopes, researchers in these few square miles produce a staggering amount of knowledge about the intricate connections inside a human cell and how they can come undone. For all the horror it causes, cancer is a fascinating intellectual problem—a window into understanding life. But only very slowly do the new findings make their way to hospital clinics, where people are being treated with chemo and radiation—techniques not much less brutal than what Solzhenitsyn described in his novel Cancer Ward. The dream teams were trying to cross the divide.

  This was part of a broader effort called translational research, which was the subject of a workshop that evening at the Parker House, the grandest of Boston’s old hotels. In a room with chandeliers and wainscoted walls, I sat among a group of young scientists who were learning about the different cultures of medical research: biologists who study the chemical cascades inside a cell, clinicians who develop and test new drugs, oncologists and the patients they are treating—they all see cancer in different ways. While the mornings would be filled with lectures, in the afternoons the students would visit cancer clinics and hospital pathology laboratories and watch over a medical ethics panel as it reviewed the rules for conducting new clinical trials—an arena in which the priorities of science and medicine often conflict.

  Amy Harmon, a reporter for The New York Times, had recently told the story of two cousins with advanced metastatic melanoma, which is about as deadly a cancer as you can get. Both young men—they were in their early twenties—were accepted into a trial for a targeted therapy, vemurafenib, which promised to shrink tumors that were driven by a mutation in a gene called BRAF. A small Phase I trial and a larger Phase II had shown promising results. Now it was time for Phase III—675 people in twelve countries—the last step before seeking approval from the FDA.

  That is where the dilemma arose. The cousins were lucky to be in the trial—only about half of melanoma cases have this particular mutation. But one of them, Thomas McLaughlin, was randomly assigned to the experimental group, which would get the new therapy (“the superpills,” he called them) while the other, Brandon Ryan, was in the control group, which would get dacarbazine, the standard and depressingly ineffective chemotherapy. Both men were dismayed by the arbitrariness of the decision. McLaughlin, whose melanoma was already Stage 4, wanted to switch places with Ryan, whose somewhat less advanced malignancy might have given him a better chance. But that was not allowed. It would compromise the objectivity of the trial.

  It was a heart-wrenching story with the good of the few bowing before the good of the many. Without rigorous comparisons like these there might be no new drugs for anyone. Still, it was hard not to think of the people in the control group as sacrificial lambs. Medical ethicists use the term “clinical equipoise” to describe a trial in which there is no a priori reason to consider one treatment superior to another. Only then, many argue, is it right to decide blindly which patient will get which drug. By the time Phase II had ended, vemurafenib appeared to blow dacarbazine out of the water, yet half the patients would now be getting what already seemed like an inferior treatment.

  In the end, Phase III proved so definitive that it was interrupted early so both groups could benefit. Initial reports showed that vemurafenib increased progression-free survival, holding the cancer in abeyance for 5.3 months, compared with 1.6 months for dacarbazine. That was enough for the FDA. Before long the drug was approved and being marketed by Genentech. At last report patients were typically living four months longer than those on dacarbazine.

  There was no happy ending. Ryan, the cousin in the control group, was among the many who had died during the first year of the trial—sixty-six in the dacarbazine group and forty-two among those getting vemurafenib. By the time another year had passed half of the people who had enrolled in the study were dead. McLaughlin’s tumors had spread throughout his body, from his thighs to his brain. But he was still alive and taking the superpills. He told me he was back at his job as a welder, working in the sun. I thought of a passage in Cancer Ward: “All the time he was running a race against the tumor to come, but racing in the dark, since he couldn’t see where the enemy was. But the enemy was all-seeing,
and at the best moment of his life it pounced on him with its fangs. It wasn’t a disease, it was a snake. Even its name was snakelike—melanoblastoma.” That is an older name for McLaughlin’s cancer.

  For advanced metastatic melanoma there is nothing that resembles a cure. No matter what the treatment, the aberrant cells discover, through a fortuitous mutation, how to continue with their expansion. Vemurafenib also has a paradoxical side effect: encouraging the growth of other skin cancers, squamous cell carcinoma and keratoacanthoma. Researchers are experimenting with combinations of targeted therapies that aim to overcome these obstacles, hoping that the cancer cells won’t develop yet another workaround.

  One of the aims of translational research is to bring scientists out of the laboratory so they can see firsthand what patients are going through. At the Parker House, Tom Curran, a professor of pathology at the University of Pennsylvania medical school, described the jarring effect of moving from the isolation of a pharmaceutical company laboratory to St. Jude Children’s Research Hospital in Memphis, where he took a job in 1995. Curran had discovered a gene called reelin, which helps direct the migration of neurons during the early development of the brain, including the cerebellum. The cerebellum is the center of muscular control and balance, and mice born with defects in the gene walk with a reeling gait. Mutations in developmental genes are also responsible later on for many pediatric cancers, and Curran was particularly interested in medulloblastoma, an aggressive cancer of the cerebellum. Compared with other cancers it is extremely rare: the prevalence among adults is 8 cases in 10 million. But there are 5 cases per 100,000 among children and teenagers, making it the most common pediatric brain tumor. The median age of diagnosis is five. What might begin as nothing more alarming than flulike symptoms can give way to headaches and vomiting, dizziness, loss of balance, and what has been described as “a clumsy, staggered walking pattern.”