Maggie is one of thousands of children who develop cancer and, through rigorous treatment and holistic care by doctors and families, beat the disease. Treatment for cancer has increased dramatically since the 1950s, and nowhere is that more evident than in pediatric oncology; of the thousands of children treated in the U.S. for cancer every year, 80 percent of them will go into remission and go on to live productive lives—significantly higher than the five-year survival numbers for general oncology, which are 63 percent chance of survival for female patients and 66 percent for men. This disparity exists in part because of biology—the types of cancers that kids get, the strength of their immune systems—and because pediatric oncologists treat patients very differently than do general oncologists. The field isn’t perfect; some of the kids who survive have health issues later in life, and curing the remaining 20 percent of patients won’t be easy. But general oncologists can learn a few things about how pediatricians achieved this remarkable cure rate, and may be able to collaborate with them to discover new, less toxic treatments to benefit patients of any age. “Childhood cancer is a different animal. Even though it has a similar end point [as adult cancers], the body in which it occurs is quite different than that of an adult,” says Alan Gamis, a pediatric oncologist at Children’s Mercy Hospital.
A ‘Mistake Of Nature’
Both childhood and adult cancers are caused by genetic mutations that cause cells to grow uncontrollably, threatening the function of the rest of the body. Adult patients can be born with mutations that combine with environmental factors to later cause disease. But kids are born with these mutations through no action of their own. They didn’t smoke for 40 years and destroy their lungs, or spend too much time without sunscreen. Childhood cancers are cases of unlucky genes, and as a result they are biologically different from those that occur in adults. The driving mechanisms are simpler, caused by only one or two mutations instead of the dozens that may be present in adult cancers.. They almost exclusively occur in rapidly dividing tissues, often in the blood, bones, kidneys, brain or nervous system. Since these tissues are no longer actively growing in adults, cancers that occur in the same organ in adults are often genetically different. “In [a child]’s proliferating tissue, a mistake occurs,” says James Downing, CEO of St. Jude Children’s Research Hospital and the chair of Childhood Cancer Treatment. Sometimes these “random mistakes of nature,” as Downing calls them, can occur even before a baby is born. And while most adult cancers grow so slowly that they can be checked every year or so, childhood cancers proliferate with terrifying speed because of the tissues in which they develop. Gamis mentions that he has seen children’s tumors double in size every eight or 12 hours. But biology can work in favor of treating the disease, too; because of kids’ fast metabolisms and general lack of other health issues, kids can tolerate a much higher dose of treatment. “Kids are far more resilient,” says Andrew Kung, the head of the Pediatric Hematology, Oncology, and Stem Cell Transplantation Division at New York Presbyterian Hospital. “If you come to our clinic, you see the kids running around, and you would not know that these are kids with cancer, except that they are bald. Whereas adults getting the same kinds of therapies would be laid up in bed.” Over time, researchers have found that this biology makes kids’ cancers much more treatable, contributing to the 80 percent cure rate. But to be able to leverage these elements of biology, researchers first had to discover viable treatments.
Seeking Treatment
Progress in treating childhood cancers has been swift. In the 1950s and early 1960s, children diagnosed with cancer would invariably die in a few months. But in the late 1950s, doctors discovered that radiation could stop cancer cells from proliferating; a few years later, in the early 1960s, others discovered that multiple rounds of aggressive chemotherapy could stop the cancer from coming back later. “In a generation, childhood leukemias went from uniformly fatal to curable most of the time,” says Douglas Hawkins, associate division chief of pediatric hematology/oncology at Seattle Children’s Hospital. Since those early days, pediatric oncologists have been fine-tuning these treatments and discovering new ones to help more kids survive, and to do so with the fewest long-term complications. “The cure for cancer didn’t happen once—it’s a continuum of learning,” Hawkins says. “Gradually, over the course of decades, we learned that we could give kids less and less radiation through clinical trials.” From the start, pediatric oncologists created a unique culture of collaboration that exists in few other places in medicine. Childhood cancers are rare diseases, affecting around 16,000 children and adolescents per year but making up only 2 percent of all cancer cases. Over the past three decades, this collaboration has coalesced most clearly in clinical trials. About 60 percent of all kids with cancer participate in clinical trials, and have done so for decades. “Every child we treat is an opportunity for us to learn and in that way continually optimize our treatments,” Kung says. Unlike for adult patients, fewer than 5 percent of whom are enrolled in clinical trials, these are the norm for children. This allows researchers to collaborate across institutions and disciplines of medicine, all in the hope of finding better ways to treat and support kids.
Experimental clinical trials are the norm for children.
This disparity between the enrollment of adults and children exists in large part because children are more often treated in university cancer centers; because there are so many more of them, adults are usually treated at their local hospitals. Adult patients often don’t even know that clinical trials are an option or if they are eligible; clinicians present less of a united front against a specific aspect of a particular disease. “We can’t get anything done as pediatric oncologists unless we work together, pool our results and talk to each other,” says Crystal Mackall, the chief of pediatric oncology at the National Cancer Institute. “Over and over again, the principles that childhood cancer teaches us turn out to be fundamental. This ability to use cooperative groups to learn about rare diseases is an important insight, as adult doctors are coming to understand.” As a result of the systematic testing and constant collaboration, many of the treatments found to work in kids have been extrapolated to adults. In a sense, all cancer patients have benefitted from pediatric oncologists’ decades of work.
Stuck Numbers
20 years ago, Kung was working in Boston when he started treating a young man named Keith who was diagnosed with a rare leukemia called acute promylocitic leukemia. It’s a very treatable form of the disease, Kung says, but just two years after treatment, the disease came back. This time, it would be much harder to treat. As Keith’s doctors were contemplating which intervention to try next—maybe chemo again, or the more aggressive and invasive bone marrow transplant—Kung heard about a new, experimental treatment based on traditional Chinese medicine. The active ingredient was arsenic, which can kill a person with just a quarter of a gram. “It was a situation where people thought we were crazy—including Keith,” Kung says, but after going over all the details, Keith was on board. The treatment worked, and Keith went into remission. 18 years later, Keith is a full-grown adult and a long-term survivor of the disease. “I’ve subsequently been to his graduations, his wedding, his divorce,” Kung says, and arsenic is now a standard treatment for some types of leukemia. “That’s an example of why [pediatric oncologists] do what we do—to be able to treat these young children and really be able to impact them, not just prolong their lives, but cure them and have them return to a normal life.” Those of us outside the field of pediatric oncology often assume that spending your career treating kids with cancer would be incredibly depressing. “When I’m at a cocktail party I say I’m a pediatrician,” Hawkins says, because he’s found that introducing himself as a pediatric oncologist tends to be a conversation-stopper. “But it’s an amazingly collaborative community. It’s incredible that people get up and speak so freely—it’s striking how willing they are to share information.” Despite the hundreds of dedicated, smart people working hard to improve treatments for childhood cancers and a cure rate that has risen in jumps and starts over time, progress has stalled for the last decade. Clinical trials are still collaborative across fields and institutions, but the number of them has shrunk. Because childhood cancers are rare and the cure rate is so high overall, funding has dried up. And though 90 percent of children with some forms of cancer can be cured, the cure rate is much lower for some other types, like neuroblastoma or osteosarcoma, and hasn’t risen in decades. “There are some diseases in which we’ve made no progress in 39 years, and no one thinks that’s OK,” Mackall says. “If we had more resources, we could do better.” “Even though cancer is rare in kids, and even though we do very well overall, there’s still a tremendous need in terms of research and funding,” Kung says. “It’s not just about doing better for the 20 percent that we’re not curing—even for the patients we do cure, over half ultimately have some sort of long-term effect attributable to the disease itself or to the treatments we have to use.” In other words, the cutting edge in pediatric oncology is two-fold: Improving the treatments already in use, and finding new treatments to cure those patients that are still slipping through the cracks.
The Good And Bad Of Treatment
As a junior in college, Maggie went to Prague to study abroad. On the fifth day of her program, she was preparing to go on a tour of a historic castle with her new friends, when she discovered that she was peeing blood. “Because I had kidney cancer and I only had one kidney left, peeing blood is really bad. I hadn’t even told my roommates yet [that I had had cancer],” she says. She spent a few days alone in the hospital in Prague and when they couldn’t figure out what was going on, her insurance company flew her back to the U.S. The issue was with her ureter, the duct that used to connect her bladder to her kidney before it was removed, and though Maggie’s doctors are still not quite sure what was wrong with it, they’re fairly certain that the issue was a result of the cancer treatment she received as a child. “It’s a medical mystery that I’m sure is related to the treatment somehow. I don’t know why else it would happen.” Later, she would have the ureter removed. That was just one of the health complications that have arisen for Maggie as she’s grown up; she’s had several incidences of basal cell carcinoma, a skin cancer, on her abdomen where she received radiation therapy as a kid. And when she was 22, Maggie found out she won’t be able to have children. “Sure, there are other options, and I always wanted to adopt, but just having my options stolen from me was completely devastating,” she says. As more childhood cancer survivors reach adulthood—some estimates that between one half and 1 percent of all kids who reach age 20 will soon be cancer survivors, Kung says—clinicians are discovering the long-term effects of these toxic treatments. “[Pediatric oncology’s] dirty little secret, and one that’s of great concern among those of us in this field, is that a sizable percentage of those children who are cured of their cancer will have lifelong side effects of their therapy. And a third of these side effects will be life threatening,” Mackall says. Some chemo drugs have been shown to affect the function of a patient’s heart or result in neurological effects like decreased IQ or attention span. Girls who received radiation therapy as kids have higher incidences of breast cancer as adults. And for some patients like Maggie, when they grow up and are ready to have children, they find that they are not able—exposure to such noxious chemicals and energies during such an important period in their development has rendered their bodies unable. Clinicians have been working to limit treatments’ effects by finding the lowest possible dose of a drug or using as little radiation as possible. But there’s only so far they can get with the same old treatments. “That’s the Holy Grail: more effective, less toxic therapies,” Mackall says. “The belief is that these will result from a biological understanding of the cancer itself.” In theory, that biological understanding will lead to new paradigms altogether—which will be necessary, since most pediatric oncologists think that curing that last 20 percent of patients is going to be more difficult since the easiest solutions have already been exhausted. General oncologists can learn from pediatrics, but information can also flow the other way. Some treatments that use small molecules, which are very effective in adults, have proven less so in kids. But researchers have seen promising results with kinase inhibitors, molecules that block the signals that tell cancer cells to divide and cause less damage to healthy parts of the body. This treatment is already known to work well on adults, but it has not yet been thoroughly tested in kids, and it’s not yet clear if the drugs will be as effective. Another promising treatment is immunotherapy, a treatment in which a patient’s own immune system attacks the cancer that would otherwise slip past it. So far researchers are seeing some amazing results in using immunotherapy to treat certain types of leukemia, raising the cure rate from 90 percent to 100 percent, Mackall says. “Time will tell, but based on what we’re seeing on patients, they seem to be able to respond to immunotherapy even when they’re not responding to chemotherapy. It adds something completely different to the [treatment] portfolio,” she adds—if it works for other types of childhood cancers, Hawkins adds. But an exciting new therapy isn’t a reason to throw the others out the window, Gamis cautions. Many cancers are very treatable with traditional chemotherapy; for now, new experimental treatments are just another tool in clinicians’ cancer-fighting toolbox. “Over the years we’ve seen paradigms come and go. So we have to be cautious about putting all our eggs in one basket,” he says. Other clinicians like Downing intend to bring the most effective treatments to other countries where the cure rate for pediatric cancers is nowhere near 80 percent. The best way, he says, is to encourage the kind of collaboration—between healthcare providers within the same country and beyond—that enabled doctors to cure more American kids decades ago. There’s no doubt that children diagnosed with cancer today fare better than those in decades past. And as more childhood cancer survivors grow up and have productive lives, clinicians see how their past treatment affects them in ways that are less tangible than physical scars. “There is a certain spirit factor, that’s what I call it, that the patients receive because of what they went through,” Mackall says. “They tend to have a very clear understanding of what life is all about and what really matters. And many of them will say that their lives have been enriched as a result. I’m not implying that they haven’t suffered, but there can be a positive psychological side.” Maggie is one of those spirited people—she’s a normal, happy woman in her mid-20s. And yet her experience fighting cancer has become a part of her. After concentrating on gerontology in college, Maggie went on to earn her masters in public health in epidemiology and now works for a nonprofit focusing on palliative care. She can’t remember what she wanted to do with her life before she had cancer, but she thinks her career choice was shaped by both her intellectual interests as well as her own trajectory. When Maggie tells people for the first time that she had cancer as a kid, she doesn’t talk about the ongoing health issues that resulted from it. “I don’t think they want to hear about the awful parts—they want to hear you’re all good now,” she says. And she hates when people tell her she’s so brave or an inspiration for surviving cancer treatment—she prefers that people say, “That really sucks.” “It shows empathy more than it shows sympathy,” Maggie says. “And, really, that’s what we all want to hear.” Cancer research and treatment has changed drastically within the past decade. In this series, “A Future Without Cancer,” Popular Science provides a context in which to understand the breathtaking pace of progress, to help you get a picture of the current state of the art of cancer treatment, diagnosis, and prevention, and where it’s likely to go next.
