Cancer as kids. Now what?
As young survivors of the modern era of cancer treatment enter the third and fourth decades of their lives, they find themselves poster children for the hope of medical progress -- and also for the toll taken by cancer’s toxic treatments.
The cure rate for childhood cancer is one of 20th century medicine’s greatest success stories. Before 1970, few children with cancer made it. Today, nearly 80% of children who have cancer are cured, according to the American Cancer Society’s 2008 statistics. Of the 11 million American cancer survivors, 270,000 have survived childhood cancer.
But they have not survived unscathed.
In a kind of cosmic kick in the pants, the treatment that once saved them can put their health at risk for the rest of their lives.
Cancer therapies injure, starve or kill healthy cells along with malignant ones, and as a consequence, survivors have a heightened risk of health problems, including early heart attacks, second cancers, stunted growth and infertility.
“It really hits home when you see a young adult who comes in with congestive heart failure because of their radiation exposure,” says Dr. Jacqueline Casillas, pediatric oncologist and director of the UCLA-Livestrong Survivorship Center of Excellenceat Mattel Children’s Hospital.
The developing brain -- and psyche -- can be affected as well. Radiation to the brain can result in a drop of 20 or more IQ points, causing learning disabilities for some. And while some cured youngsters enter adulthood feeling a renewed sense of purpose, others must deal with lingering bitterness and trauma from their treatment, which can emerge as depression or anxiety when they become adults.
Doctors are using the experiences of these young survivors to try to make things better for new generations of pediatric cancer patients. They are also coming to realize they must do better by young people whose cancer lies behind them. Only recently is the medical community understanding the importance of lifelong health monitoring to help them avoid, or detect early, the host of medical risks that could lie in their path.
That often isn’t easy. By the time the consequences hit, many young survivors have worked hard to forget the cancer experience. “Some survivors of childhood cancer, when they become adults, don’t ever want to see another doctor again,” says Anne Kazak, director of the department of psychology at the Children’s Hospital of Philadelphia.
Later effects vary
The long-term consequences of cancer treatment vary tremendously, depending on the type of treatment, dose of drugs or radiation, and age and sex of the child.
Children who were treated with radiation to the brain are at future risk for growth hormone deficiency, learning deficits, seizures, strokes and cataracts. Those whose chests were radiated are at risk for breast cancer, thyroid cancer and lung cancer; those who received radiation in the pelvic area could suffer bladder disease, kidney disease or infertility.
Various chemotherapy drugs are linked to infertility, early menopause in females, leukemia, kidney disease, hearing loss, heart disease and lung disease.
Precise statistics vary, because combinations of drugs, or drugs paired with radiation, can increase the risks, as do higher treatment doses.
But it’s known that up to half of females who received high doses of chest radiation, for example, will have breast cancer later in life (and should have a mammogram every year starting at age 25).
And a study of 14,000 childhood cancer survivors, reported this month at a meeting of the American Society of Clinical Oncology, found a five to 10 times greater risk (compared with healthy siblings) of developing heart disease in early adulthood.
Children treated for leukemia at preschool age are four times more likely to be enrolled in special education programs than their siblings, according to research cited in a 2003 Institute of Medicine report called “Childhood Cancer Survivorship: Improving Care and Quality of Life.”
Studies have also found that symptoms of post-traumatic stress such as nightmares or flashbacks affect up to 40% of childhood cancer survivors -- with 16% of survivors receiving a diagnosis of full-blown post-traumatic stress disorder. And 17% of young survivors suffer from depression, anxiety or insomnia, a rate roughly twice what is seen in people their age who did not have cancer.
The tragic bottom line is that about two-thirds of childhood cancer survivors experience at least one late health effect of treatment, and for more than one-quarter of survivors it is severe or life-threatening, according to a 2006 report in the New England Journal of Medicine.
Researchers have begun studying these grown-up “miracle” kids, the ones who made it at a time when thousands like them didn’t, to find ways to make survival less risky for today’s young cancer patients.
Not so long ago, the desperation to cure children was so intense that physicians were willing to throw everything in their medical arsenal at childhood cancer. In the all-out fight for life, there was little room to consider future consequences.
Increasingly, treatments take future quality of life into account, though cure remains the top goal. But whether to ease up on toxic treatments or continue to pull out all the stops remains a difficult balancing act, says Dr. Archie Bleyer, adolescent and young adult oncologist in Bend, Ore.
To better understand and prevent these medical problems, in 1993 the National Cancer Institute started the Childhood Cancer Survivor Study of about 14,000 patients who had cancer as children between 1970 and 1986, comparing their health with that of their siblings who did not have cancer. By cataloging their medical problems and linking them to anti-cancer treatments, researchers have begun to experiment with modifying those treatments in the hope of reducing medical consequences in future survivors of childhood cancer.
Sometimes, the modifications have worked. Almost all childhood leukemia patients, for example, once received brain radiation. Now, although some patients still require such treatment, in most cases chemotherapy drugs are delivered through the spine. The new procedure maintains the same cure rate while reducing the risk of brain damage and future learning problems.
Children with Wilms tumor, a childhood kidney cancer, are no longer routinely treated with radiation to the abdomen. With no sacrifice in cures, “the children have been able to grow better, have less skeletal abnormalities such as scoliosis, decreased liver failure and improved kidney function,” Bleyer says.
Tragically, in trying to walk the tightrope between cure and quality of life, some youngsters have died. “There has been a downside to this,” Bleyer says. “We’ve tried to reduce late effects, but sometimes have gone too far. It has become known as killing with kindness.”
He has a troubling memory of one clinical trial he led. In the experiment, leukemia patients who responded quickly and well to the initial phase of chemotherapy were divided into two groups. One group received standard follow-up treatment: three years of additional doses of four drugs thought to ensure that all cancer cells are killed. The second group, to test whether children would do just as well with fewer drugs in the follow-up phase, received only two of the four drugs.
But the trial was halted when it became clear that those who got the reduced drug therapy were suffering relapses. Some in the experimental group later died; all those in the standard treatment group survived. “We learned that we cannot identify the group that can have treatment reduced,” Bleyer says.
The same negative outcome occurred when children with osteosarcoma, bone cancer that often results in limb amputation, were not given chemotherapy after surgery. Many physicians believed that chemo was unnecessary, until a clinical trial proved that those who didn’t receive it were more likely to have a recurrence. Again, some kids died.
“We’ve tried to cut back on side effects, and we’ve lost some kids,” Bleyer says. “It’s the history of cancer treatment.”
Another National Cancer Institute-funded experiment is now underway to test whether some children with Hodgkin’s lymphoma who respond exceptionally well to chemotherapy can safely avoid follow-up radiation, which puts girls at very high risk for future breast cancer. “Can rapid responders be spared that? Can we continue to maintain high cure rates?” Casillas says. “We don’t have the answer yet.”
Follow-ups urged
Because there is so much variation in individual patients, the Institute of Medicine’s overall recommendation in its 2003 report on childhood cancer is that all pediatric cancer patients be told what treatment they received and get individualized advice on what to do in the future.
Such planning still falls short. A study presented at the 2007 meeting of the American Society of Clinical Oncology reported that of 8,500 childhood cancer survivors whose average age was 31, only 18% received the kind of risk-based medical follow-up recommended. Among survivors at increased risk for breast cancer, for example, only 49% had had a mammogram. And of those at increased risk for heart disease, only 28% received an echocardiogram.
Part of the problem is that when children are cured of cancer, they leave their pediatric oncologists -- the doctors who know the most about their condition -- behind them. And general physicians, even specialists, may not be aware of the unique care required for cancer survivors.
“What primary care physician is going to routinely recommend a mammogram for a 25-year-old?” says Dr. Patricia Ganz, director of cancer prevention and control at UCLA’s Jonsson Comprehensive Cancer Center.
The patients themselves are understandably reluctant to hold onto cancer memories. “These young folks want to put the cancer behind them and be like everyone else,” Ganz says. “But we’re also telling them, ‘You’re not normal.’ They’ve survived this experience, but they have these risks.”
Once cancer, and childhood, are behind patients, the general physicians who treat them as adults need detailed records on past drug doses, age of treatment or exposure to radiation to be aware of the unique needs of survivors.
They also need to be provided with information on the increased risks the survivors may face because of their cancer treatments. That way, physicians who might have few cancer survivors in their practices will understand that illnesses of middle and old age can appear sooner in this group.
“An adult cardiologist will be familiar with cardiac patients but may not be up to date on heart problems in childhood cancer survivors,” Casillas says.
For young adults whose treatment occurred decades ago, gathering the old information isn’t easy. “We’ve seen patients who were treated in New York, in Israel,” Casillas says. “It is often very challenging to get the medical records. Their oncologist may no longer be practicing, or even alive.”
Parents, traumatized by almost losing their children, can be poor sources of information too, as eager as their growing kids to put the experience behind them. “Some survivors don’t even remember their cancer experience,” Casillas says. “Sometimes, parents don’t even tell their children that they had cancer. We try to piece the record together as best as we can.”
Such challenges are why many institutions have experts to help ease pediatric patients, and their records, into the adult medical world. (Locally, these include the UCLA-Livestrong Survivorship Center of Excellence at Mattel Children’s Hospital, USC’s LIFE Survivorship and Transition Program, the Children’s Hospital of Orange County’s Long-Term Follow-Up Clinic and the City of Hope National Medical Center’s Childhood Cancer Survivor Program.) The programs also see adult patients who were treated for childhood cancer at other centers.
Ganz, for example, strives to help adult survivors of childhood cancer develop individual long-term medical plans, a road map for care that they can show to every doctor in their future. Depending on their treatment history, it could include earlier than normal mammograms, echocardiograms or blood glucose tests.
Patients, as they enter adulthood, should arm themselves with the most complete and detailed copies of their medical records they can gather. And parents of children who are recovering from cancer now can familiarize themselves with the likely future health issues and begin to prepare.
For learning problems, special education programs can help kids catch up. The 2003 Institute of Medicine report on childhood cancer survivors found that they had the same rate of high school and college graduation as their siblings, suggesting that, with special education classes, most were able to overcome the early learning deficits.
Parents can also be on the lookout for mental health problems. “We tell parents and patients that just because the most intensive part of treatment is over doesn’t mean you’re going to feel wonderful psychologically,” Kazak says. “You have to deal with new problems that you didn’t understand early on.”
An important, and nonmedical, part of preparing for life after childhood cancer is getting a good education that leads to a good job -- and that means a job with health insurance. At about age 21, childhood cancer survivors fall off their parents’ health insurance plans. The lifelong “pre-existing condition” of childhood cancer could make individual health insurance unattainable or unaffordable.
“How do they find a vocation that’s going to be rewarding but will provide them with good pay and benefits? That means completing education,” says Dr. David Freyer, director of the LIFE Survivorship and Transition Program at Childrens Hospital Los Angeles. “We encourage them to stay in school.”
Children surviving cancer have made it through a harrowing medical experience. They’ll need a job. And they’ll also need to understand fully what happened to them -- some when they were too young to know -- and how it affects their future.
“What happens to people we’ve made infertile? What happens to them psychologically? What happens medically?” says Dr. Leonard Sender, medical director of the Children’s Hospital of Orange County Cancer Institute. “We’re getting cures. Now we owe it to them to help them survive.”
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