Center News Magazine: Late Effects of Childhood Cancer Treatment

Friday, May 1, 2009
Kevin Oeffinger, Director of the Program for Adult Survivors of Pediatric Cancer, recently found evidence that childhood cancer survivors and their physicians may not be sufficiently aware of the 
long-term effects of their treatments. Kevin Oeffinger, Director of the Program for Adult Survivors of Pediatric Cancer, recently found evidence that childhood cancer survivors and their physicians may not be sufficiently aware of the
long-term effects of their treatments.

Raising Awareness, Reducing Risk

Childhood cancer in the United States now has a five-year survival rate of 80 percent. Thanks to improved methods of treatment, most pediatric patients grow up to lead active lives. But they are also subject to future health risks. Nearly three-quarters of childhood cancer survivors will develop a chronic health problem within 30 years of diagnosis.

These secondary conditions are often delayed effects from cancer treatments such as radiation or chemotherapy. This issue has taken on more importance as the number of pediatric cancer survivors has increased — to more than 300,000 Americans, or about one in every 500 young adults. And there is striking evidence that childhood cancer survivors and their physicians do not fully appreciate these late effects or the steps that must be taken to reduce the risks and to identify them early.

For example, a study reported in the January 28 issue of the Journal of the American Medical Association (JAMA) found that most young women who are at an increased risk of breast cancer due to chest radiation for childhood cancer are not following screening recommendations. These women are advised to start having mammograms every year beginning at age 25 or eight years after radiation, whichever comes last. But the JAMA study, led by Kevin C. Oeffinger, Director of Memorial Sloan Kettering’s Program for Adult Survivors of Pediatric Cancer, found that among women aged 25 through 39, only 36.5 percent had had a screening mammogram within the previous two years. The subjects were participants in the Childhood Cancer Survivor Study (CCSS), a multi-institutional patient group made up of long-term cancer survivors diagnosed with a pediatric malignancy between 1970 and 1986.

To Dr. Oeffinger, this finding does not indicate that childhood cancer survivors are willfully ignoring the guidelines. Rather, it suggests that neither these patients nor the clinicians following them are sufficiently aware of the risks or the recommendations. “As cancer centers, we have not disseminated this information as well as we could and equipped survivors and their physicians with the knowledge they need to make the best decisions,” Dr. Oeffinger said.

Lingering Health Effects

The JAMA finding highlights the need to raise awareness about the late effects of childhood cancer treatment. The pervasiveness of late effects became clear in 2006 when a CCSS study led by Dr. Oeffinger and published in the New England Journal of Medicine (NEJM) found that 73.4 percent of pediatric cancer survivors will develop a chronic health problem within three decades of diagnosis, with 42.4 percent experiencing severe, life-threatening, disabling, or fatal conditions, such as heart attacks and second cancers.

However, these outcomes are not limited to a handful of conditions. “What you see is that there are not really one or two things that are common — it’s a variety of problems that occur,” Dr. Oeffinger explained. The health complications are usually driven by the type of treatment rather than the particular type of cancer; children who receive similar therapies will be at risk for similar problems later in life regardless of their diagnosis.

For example, radiation to the chest — which has been standard therapy for Hodgkin lymphoma for many years — can not only raise the risk of breast cancer, it also can damage the coronary arteries in ways that accelerate the development of heart disease. Radiation to the brain early in life, a common treatment for most brain tumors, can raise the risk for cognitive disabilities, slowed growth due to loss of pituitary function, and — especially for young girls — early puberty.

Chemotherapy also causes a variety of problems, depending on the agent that is used. Some chemotherapy drugs can produce kidney or hearing disorders, impair fertility, or raise the risk of secondary cancers. One particular class of chemotherapy drugs, anthracyclines, can damage heart muscles, although the condition may not become evident for 15 or 20 years.

The long-term health problems have become a major issue because of medicine’s success in treating the primary disease. “As soon as we start talking about risk, I always remind people that if we don’t cure the cancer, talking about late effects is irrelevant,” Dr. Oeffinger said.

Commitment to Ongoing Care

Charles Sklar Charles Sklar, Director of the Long-Term Follow-Up Program, develops care plans for pediatric cancer survivors to help them monitor for specific health problems.

Memorial Sloan Kettering has long recognized the importance of managing chronic medical conditions in pediatric cancer patients. In 1990 the Department of Pediatrics established the Long-Term Follow-Up Program, led by Charles A. Sklar, to help children and families navigate this path. (Dr. Sklar was a co-author on the 2006 NEJM paper regarding late effects.) The program offers follow-up medical care to pediatric cancer survivors who have been off treatment for at least two years.

When we see a child for the first time, we develop a care plan based on his or her past treatments and age at the time of treatment,” said Dr. Sklar. “The plan details the tests that should be done to monitor for specific problems and how frequently they should be performed.

As these patients grew older, Memorial Sloan Kettering recognized there was a need for an extension of the Long-Term Follow-Up Program to care for them as adults. Richard J. O’Reilly, Chair of Memorial Sloan Kettering’s Department of Pediatrics, recruited Dr. Oeffinger in 2005 to head the program for adult survivors. Now, when children in the Long-Term Follow-Up Program reach their late teens or early 20s, they transition into Dr. Oeffinger’s program. “There are very few institutions in the world that offer this kind of continuum of care,” Dr. Sklar said.

In addition to Memorial Sloan Kettering patients transferring from the Long-Term Follow-Up Program, between 25 and 30 percent of the adult patients coming to Dr. Oeffinger’s program were treated for their pediatric cancer at other institutions. “We sometimes see patients coming for their first visit to Memorial Sloan Kettering in their 40s and 50s because they had cancer in their teens,” Dr. Oeffinger said.

Drs. Sklar and Oeffinger usually see the patients once or twice a year, depending on their conditions and health risks, and they work with the patients’ other Memorial Sloan Kettering physicians and their personal physicians to coordinate care.

Both Dr. Sklar’s and Dr. Oeffinger’s programs fall under the umbrella of Memorial Sloan Kettering’s Cancer Survivorship Program, a Center-wide initiative established in 2003 to address the long-term consequences of cancer and its treatment. The Cancer Survivorship Program is directed by Mary S. McCabe, who came to Memorial Sloan Kettering from the National Cancer Institute.

Ms. McCabe said that it was only in recent years that adults who have survived cancer have become the subjects of increased focus, regardless of their age at diagnosis. She explained that adult survivors of pediatric cancer are a subset of cancer survivors who can present unique challenges.

They may not remember what treatments they received or even the names of those who treated them,” Ms. McCabe said. “Many young adults do not have health insurance. Parents, if they are available, may not understand the importance of providing specific health information. Neither the patient nor the parents may realize the need to be closely followed, and they are often resistant to revisiting a stressful period in their lives.

Preventive Measures

The increased appreciation of the late effects of cancer treatments has compelled physicians and survivors to take steps to minimize their impact. Like the Long-Term Follow-Up Program, the Program for Adult Survivors of Pediatric Cancer develops a care plan for each new patient it sees to arrange for adequate screening, surveillance, and prevention.

The plan might call for frequent screening for breast or colon cancer, or echocardiograms to check heart function. “A cancer treatment can, in effect, take whatever a person’s genetics and lifestyle would have predicted and move it up by 15 to 20 years,” Dr. Oeffinger said. “People don’t typically think of a 30-year-old female with chest pain as having coronary artery disease, but we would take it seriously and be extra vigilant about any new symptom.

Depending on the specific condition, it may be possible to delay or prevent a health problem. Survivors are sometimes given medications to prevent early puberty, to compensate for an underactive thyroid, or to offset a deficiency in growth hormone. Other measures are oriented toward preventing complications that may not emerge for decades.

For someone whose treatment put him or her at risk for heart disease, we can be very aggressive in lowering cholesterol or high blood pressure,” Dr. Oeffinger explained. “As we tell our patients, our goal is to keep them alive until their 99th birthday. After that, they’re on their own.

Even if nothing can be done to reduce the risk of a late effect, it helps to prepare patients and their families for what may lie ahead. “If everybody is aware of these problems from the beginning, the families are better able to handle them psychologically, as opposed to a patient who expects that everything is going to be fine and then all of a sudden is not — leaving him or her shocked and upset,” Dr. Sklar said.

Refined Treatment Methods

Richard O'Reilly In more than 30 years of treating patients, Richard O’Reilly, Chair of the Department of Pediatrics, has seen childhood cancer therapies change dramatically.

The challenge for physicians is finding ways to save children from a deadly disease while preserving long-term well-being. As the links between certain therapies and late effects have become clear, researchers and physicians have refined many treatments. Dr. O’Reilly, who has been treating pediatric patients for more than three decades, has witnessed this transformation firsthand.

Certain therapeutic approaches have changed pretty dramatically,” he said. “The classic example is the use of anthracyclines. After it was recognized that high doses of these drugs could cause cardiac complications, it led to the national establishment of clear limits for exposure.

For other chemotherapy drugs, he added, there is now much more recognition that individual children may vary significantly in terms of how the agents act and the speed with which they are cleared from the body. For example, physicians at Memorial Sloan Kettering and elsewhere now pay careful attention to how the chemotherapy drug methotrexate is being processed in a pediatric patient. One child may tolerate a given dose well, while another child given the same dose will suffer from toxicity. “More and more, people are thinking that this is important in terms of late toxicities as well,” Dr. O’Reilly said.

Radiation therapy approaches have been altered too. Research has shown that reducing the dose and/or shrinking the radiation field can lower the risk of late effects while being just as effective against cancer. In some cases, new forms of chemotherapy are being used as a substitute for radiation altogether.

One very important advance, Dr. O’Reilly explained, is the improved ability physicians have to define whether a child has a high-risk or low-risk form of disease. “Our capacity to evaluate patients up-front means that the proportion exposed to the high-intensity therapies — and thus more at risk for late effects — is radically reduced,” he said.

He added that the incorporation into treatment plans of genetic information, both from the cancer cells and from a patient’s normal cells, is also going to play an important role in the reduction of late effects. For example, genetic information from cancer cells is already being used to guide treatments for children with leukemia and cancers of the bone and for adults with certain lung cancers. In the future, the genetic profile of the patient’s normal cells will also provide information about whether a particular treatment will cause more or less toxicity, both in the short and long terms.

Training and Education

Mary McCabe Mary McCabe is Director of Memorial Sloan Kettering’s Cancer Survivorship Program, which addresses the long-term challenges of life after treatment for cancer.

As awareness of late effects has grown, Memorial Sloan Kettering is looking for ways to foster expertise in the field. The Center is establishing a new postdoctoral fellowship in pediatric cancer survivorship, set to begin in July 2009. Dr. Sklar says it is the first such fellowship in the country — perhaps in the world.

We want to train the next generation of clinical researchers to provide optimal care for this patient population and also advance the research,” he said.

Ms. McCabe added, “We view this as a real opportunity to prepare leaders in this area. We want to see the same emphasis that has been put on diagnosis and treatment of pediatric cancers to be given to good quality of life after treatment. People not only want to live, they want to live well.