As childhood cancer treatments have become more successful, more and more patients are surviving to adulthood. In fact, the National Cancer Institute estimates that one in nearly every 500 adults in the United States between ages 20 and 45 is a survivor of childhood cancer.
With longer survival, there’s more chance that young patients will experience the late effects of their cancer treatments as they get older.
Dr. Leonard Toonkel, chairman of radiation oncology at Mount Sinai Medical Center in Miami Beach, is familiar with childhood cancer treatments. “We think about the side effects all the time, whether it’s children or adults we treat,” he says.
There is good news, however. Progress is being made in detecting and preventing the problems of late effects.
“To treat cancer, you need to use very powerful drugs with powerful side effects. We need to be alert for these expected and unexpected side effects of cancer therapies that might manifest later in life,” says Dr. Gervasio Lamas, chief of the Columbia University division of cardiology at Mount. Sinai Medical Center in Miami Beach.
That has led some doctors to redefine childhood cancer survival, says Dr. Steven Lipshultz, a professor of pediatrics at the University of Miami Miller School of Medicine and a member of the Sylvester Comprehensive Cancer Center.
He and many of his colleagues believe it should be more than not having measureable cancer for five years. “It also should include having the fewest toxicities and late effects of cancer and its therapies,” he says.
Late effects can involve just about every system of the body including the thyroid, heart, brain, lungs, pituitary and hypothalamus, kidneys, bones, lungs and reproductive organs.
They are not easy to study because they can occur 20 to 30 years after the initial cancer. Lipshultz and his colleagues were among the first to recognize the associations between childhood chest radiation therapy and later cardiovascular problems.
“We are just now seeing the first generation of survivors of childhood cancer reaching that age where we can see what some of these late effects are panning out to be,” he says.
That’s because in 1969, only 4 percent of children diagnosed with advanced leukemia were free of leukemia five years later – 96 percent died or had cancer again. Survival rates weren’t much better than they were in the 1940s.
In the early 1970s, children’s cancer specialists throughout the nation decided to work together to improve treatments, developing the cooperative group treatment protocols for childhood cancer.
“What has happened since is one of the biggest miracles in pediatric medicine,” says Lipshultz, who is the George Batchelor Professor of Pediatric Cardiology and the director of the Batchelor Children’s Research Institute.
Now, 80 percent of all children diagnosed with cancer in the United States and 90 percent diagnosed with leukemia are surviving. And those treated in the late 1970s and 80s are just now old enough to experience some of the late effects of their childhood cancer therapies.
Lipshultz and his team have been following this first generation of long-term survivors of childhood cancer. He presented his findings at the annual meeting of the American Society of Clinical Oncology (ASCO), held last month in Chicago.
Through clinical studies using long-term randomized, controlled trials, they explored how to prevent heart damage in childhood cancer patients treated with doxorubicin - a commonly used chemotherapy also known as Adriamycin.
The work was done at the University of Miami Department of Pediatrics’ Batchelor Children’s Research Institute and the Sylvester Comprehensive Cancer Center.
The studies were designed to discover if dexrazoxane hydrochloride, a drug that binds iron in the blood, could be administered 30 minutes before the doses of doxorubicin to prevent the formation of free radicals in young patients.
Doxorubicin kills cancer cells by entering their DNA and preventing them from dividing further. “It acts like a roadblock or barrier to their dividing and that kills the cancer cells,” Lipshultz says.
But the drug also damages heart muscle cells by binding with iron in the blood to make free radicals, molecules that have been linked to heart disease and other chronic conditions. “The free radicals are like bullets to your heart tissue,” he says.
They also studied whether dexrazoxane would protect children’s hearts if they were given larger doses of doxorubicin for osteosarcoma, a difficult-to-treat bone cancer.
And they researched using dexrazoxane to protect the hearts of children given two heart-damaging drugs, Herceptin (trastuzumab) and doxorubicin. These are used to treat metastatic osteosarcoma, another hard-to-treat bone cancer.
Lipshultz and his co-workers spent many years following the progression of heart disease in study participants. During that time, they didn’t know which patients as children were given dexrazoxane before the doxorubicin and which were given just doxorubicin.
“But when one study ended after 18 years, the findings were miraculous,” he says. The hearts of patients who received the dexrazoxane were normal.
“As a result of these studies, more kids can be cured of cancer with less toxicity and late effects. It is amazing and it’s the coolest thing because now we can give life where there was death,” he says. “It doesn’t get better than that.”
When it comes to breast cancer, researchers from Memorial Sloan-Kettering Cancer Center in New York issued an important paper at the ASCO meeting. They reported that women who between 1970 and 1986 received radiation to parts of their chests during treatment for childhood cancers had a 24 percent risk of developing breast cancer by age 50.
That compares with the average woman who has a 4 percent chance. And those given larger doses of radiation, like that used to treat Hodgkin’s lymphoma, increased their risks to 30 percent. This becomes particularly critical for women who have the breast cancer type 1 susceptibility protein (BRCA1) gene mutation that is associated with an increased risk of developing breast cancer.
Women treated with chest radiation for childhood cancer who have this gene have more than a 30 percent risk of developing breast cancer by age 50.
The research suggests that female survivors of childhood cancer who received even moderate amounts of chest radiation as children should get mammograms and chest MRIs starting at age 25.
Lamas finds these results potentially lifesaving. He replaced the mitral valve of a young woman 10 years after she was treated for childhood Hodgkin’s lymphoma.
“When I saw these late effects breast cancer results, I realized I had not discussed breast cancer with her. But now I will,” he says.
Talking to patients about potential late effects has to be done in a very matter-of-fact way, he says. “They’ve been through a horrendous, life-changing experience as children and the last thing you want to do is frighten them or bring back the fears that they had,” he adds.
Parents also should get involved in limiting late effects by keeping detailed records of their child’s cancer treatments and making that information part of their youngster’s medical history.
“Even if you’ve just had a lot of diagnostic X-rays to any area of your body, your primary care physician should be aware of those,” Toonkel says.
Lipshultz recommends that if you have cancer treatments in childhood, you should protect yourself with checkups and screenings, be more physically active, eat well, and be educated about possible late effects. “When you get a diagnosis of childhood cancer, you want to be thinking about lifetime risks right from day one,” Lipshultz says. “You want to be in control of your life.”