Nick Dustman of Jacksonville, Fla., was 16 when he had a lump removed from under his right ear. Earlier, two doctors had dismissed family concerns that the lump might be something serious. When the pathology report showed the cells to be atypical, the sample was sent to St. Jude Children’s Research Hospital in Memphis, Tenn., where Dustman received a diagnosis of Hodgkin lymphoma, a cancer of the immune system that accounts for about 4 percent of all childhood cancers.
Five years after receiving radiation treatment to the chest and neck at St. Jude, Dustman was declared cancer-free.
Decades later, however, the specter of Dustman’s treatment reappeared as breathing difficulties. A long-time athlete, Dustman found it increasingly difficult to catch his breath while exercising. His doctor suspected asthma and prescribed an inhaler, which proved ineffective.
“One day, during a run in Baltimore, my breathing became painful, and I had difficulty getting enough air,” Dustman recalls. “I thought I was developing fibrosis of the lungs, which I knew was a potential side effect of radiation treatment.”
Dustman, only partially correct, learned that his health issues were indeed related to his cancer treatment, but it wasn’t fibrosis—he had developed angina from radiation-related coronary artery disease. The diagnosis was confirmed at St. Jude in 2009 when Dustman returned for the St. Jude LIFE Study, the hospital’s ongoing childhood cancer survivorship research program.
“I ended up having a six-vessel cardiac bypass,” Dustman says. “The doctors told me that when you look at my clinical report, you can see exactly where the radiation had penetrated—it was in very specific patterns.”
Dustman, now 45 and a sales director for a pharmaceutical company, is among the estimated 395,000 survivors of childhood cancer living in the U.S. He’s also one of more than 2,400 former childhood cancer patients to date who have taken part in the St. Jude LIFE Study, the first large population of survivors to be evaluated using a comprehensive systematic clinical assessment to determine the prevalence of chronic health outcomes.
Following the children long-term has not only given the oncology community a glimpse of the late effects of their treatment and how better to prepare patients, it has also impacted the way children are treated today, says Melissa M. Hudson, director of the cancer survivorship division at St. Jude.
Hudson is the lead author of a recent report appearing in the Journal of the American Medical Association (JAMA) regarding health outcomes among adults treated for childhood cancer. In the St. Jude cohort of 1,713 survivors, 98 percent had at least one chronic health condition. And of that number, an estimated 68 percent had health issues that could be considered serious, disabling or life-threatening.
Cheryl Moring, 51, of New Edinburg, Ark., is also participating in the study. She developed an unusual growth behind her ear at age 5 in 1967. At St. Jude, doctors diagnosed her condition as acute lymphoblastic leukemia and told her parents she had six months to live.
Moring’s cancer went into remission following chemotherapy but returned a year later. “The cancer cells had gotten into my central nervous system, so I received several rounds of cranial radiation,” Moring recalls. “In 1972, I was considered cured, but I continued to go back to St. Jude for regular checkups until I was into my teens.”
Though the cranial radiation saved Moring’s life, it later affected her hearing. The problem started in high school and became more serious in college, requiring her to use a hearing aid. Today, Moring reports a 65 percent hearing deficit in her left ear and a 35 percent loss in her right ear.
Infertility was also a concern, but Moring, an elementary art teacher, was lucky—her reproductive organs were unaffected by the radiation and chemotherapy, and she is now the mother of two sons and a daughter.
The late effects experienced by Dustman and Moring are fairly typical for the treatments they received, especially decades ago when treatments were harsher and less selective. According to the JAMA analysis, the most common late effects among adult survivors of childhood cancer include abnormal pulmonary function, hearing loss, endocrine problems (including thyroid and gonad disorders, which affect hormones), reproductive issues, heart conditions, neurocognitive impairment, liver dysfunction, kidney dysfunction and skeletal disorders.
Years of study into late effects experienced by survivors of pediatric cancers have changed how children receive treatment for cancer today. “Our understanding of late effects after treatment for pediatric cancer has been one of the most influential motivators for change in therapy, and specifically moving into treatments that we believe will cause fewer long-term and late effects,” Hudson says. “We now recognize that we can’t trade one chronic or potentially life-threatening disease for another.”
Indeed, because cancer specialists better understand the late-effect risks posed by chemotherapy, radiation therapy and other treatment options, they strive to create treatment plans that minimize the danger.
“One specific example is a reduction in the amount of radiation to the chest to prevent the risk of breast cancer among women,” says Smita Bhatia, director of the Center for Cancer Survivorship at City of Hope National Medical Center in Duarte, Calif. “Another is a reduction in the amount of radiation given to the brain, and even a cessation of use of radiation to prevent the development of late-effect leukemia.”
Oncologists also are using much smaller doses of anthracyclines, a family of antibiotics traditionally used to treat acute myeloid leukemia, acute lymphoblastic leukemia, bone tumors and certain soft-tissue sarcomas. While an effective treatment, anthracyclines have been linked to serious late effects, including heart failure. “These drugs are still used, but more cautiously,” Bhatia notes. “Researchers are working to develop new treatment protocols that would eliminate the use of anthracyclines completely, but that’s still years away.”
Certain types of childhood cancer appear to pose a greater risk for late effects than others, primarily because of their treatments, according to the National Cancer Institute. Among the worst is Hodgkin lymphoma, for which treatment—typically radiation and chemotherapy—can dramatically increase a patient’s risk of heart and lung problems, second cancers and other health issues. Another example is radiation or anthracycline treatment for acute lymphoblastic leukemia, acute myeloid leukemia, brain and spinal cord tumors and head and neck cancer, which can result in heart, blood vessel and neurologic late effects.
Radiation is associated with a variety of second malignant neoplasms, including breast cancer (if the breast was in the original field), colon cancer and skin cancer, says Emily Tonorezos, clinical coordinator of the adult long-term follow-up program at Memorial Sloan-Kettering Cancer Center in New York. “Recurrence and second tumors are the No. 1 and No. 2 issues among these patients,” she says.
Radiation is also linked to neurocognitive disorders, learning disabilities and other issues when used to treat cancers of the brain and head.
Chemotherapy, which can be particularly toxic to young organs and systems, can also result in certain late effects, especially when combined with radiation therapy, researchers report. Late effects associated with chemotherapy include cataracts, early menopause, heart problems, infertility, liver problems, osteoporosis, reduced lung capacity, lung disease and increased risk of other cancers, according to the Mayo Clinic.
Additional factors can also influence the development of late effects, including the combination and length of treatment, and the patient’s age at the time of treatment. “Age is important and, generally speaking, younger children are more vulnerable to late effects,” Hudson says. “But there are conditions in which older patients are more vulnerable, and you have to consider all of those other factors.”
Making matters worse, late effects can take a significant psychosocial toll if the resulting physical limitations, cognitive changes or other issues make it difficult for a cancer survivor to go to school, get a job or maintain a relationship.
“We have affected functional outcomes, we have affected their cognitive skills, and that takes an emotional toll,” Hudson says. “It is important for us to understand what makes those individuals more vulnerable and what we can do to identify those individuals earlier, so we can ensure that resources are provided for them to preserve their health and improve the quality of their survival.”
One of the most insidious aspects of late effects is that they take so long to develop, Tonorezos says. “If something happens immediately after treatment, we usually think of that as a primary effect of the treatment itself,” she explains. “But if a patient starts experiencing something six or more months after treatment, that’s what we think of as a late effect.”
In many cases, a childhood cancer survivor’s health in adulthood is also influenced by lifestyle choices, such as smoking, sun exposure, lack of exercise, diet and alcohol consumption. Age and a predisposition to common health problems unrelated to cancer, such as high blood pressure, can also muddy the diagnostic waters.
“One of the goals of health outcomes research in cancer survivors is to understand the factors that contribute to an individual’s overall health after treatment for childhood cancer,” Hudson says. “How do all these factors, including genes and family predispositions, as well as health behaviors and aging, affect the risk of disease in a population already made more vulnerable by these treatments?”
If a patient starts experiencing something six or more months after treatment, that’s what we think of as a late effect.
At City of Hope, researchers are investigating several experimental interventions they hope will reduce the risk of late effects and benefit long-term health, says Bhatia, who is the project’s senior investigator. They include a drug designed to reduce the risk of breast cancer among women who received radiation to the chest in childhood; a drug designed to reduce the incidence of heart failure among childhood cancer patients who received anthracyclines, and an investigation into whether the vaccine for human papillomavirus can reduce the risk of cervical cancer among female childhood cancer survivors.
“This kind of research is important because we have learned over the years that the burden of morbidity among childhood cancer survivors is very, very high,” Bhatia says. “We need to do something to mitigate this, and these approaches show promise.”
Survivors of childhood cancer are encouraged to undergo lifelong medical monitoring and to report any indications of late effects. Despite this recommendation, fewer than one-third of adult survivors see their primary oncology team or current care provider for regular follow-up, Tonorezos says. Many relocate or fail to stay in touch with their childhood cancer specialists. Others lack insurance or simply don’t want to go through the hassle. And some, because they feel healthy, don’t see a need for routine health monitoring.
Tonorezos recommends that adult survivors of childhood cancer create a cancer treatment summary, a document detailing the types of treatment they received and when, dosages, and where on the body treatment was performed. This information, which can be obtained from a patient’s original oncology team, treatment hospital and sometimes even family members, can greatly help a patient’s primary care provider monitor for late effects and address them early on should they occur. If the patient is no longer in touch with the original team, or for some reason cannot obtain original records, they should create their own treatment summary with whatever information they can obtain or recall.
Several organizations offer survivorship care plans that can be accessed online. The best source for specific pages to document every aspect of treatment is provided by the Abramson Cancer Center of the University of Pennsylvania at oncolink.org/ oncopilot. In addition, Memorial Sloan-Kettering Cancer Center’s Survivorship Guide has a two-page summary of treatment and follow-up plan. Log on to mskcc.org and type “survivorship care plan” in the search field for details. Or check the American Society of Clinical Oncology’s treatment summary at cancer.net/ survivorship/asco-cancer-treatment-summaries.
“A comprehensive summary of a patient’s cancer treatment is extremely important,” Tonorezos says. “Once you have that, you can use the Children’s Oncology Group long-term follow-up guidelines, which can be found at survivorshipguidelines.org. It is a comprehensive document that outlines what follow-up care is required for each type of therapy.”