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National Cancer Policy Forum; Board on Health Care Services; A Livestrong and Institute of Medicine Workshop; Institute of Medicine. Identifying and Addressing the Needs of Adolescents and Young Adults with Cancer: Workshop Summary. Washington (DC): National Academies Press (US); 2014 Jan 10.

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Identifying and Addressing the Needs of Adolescents and Young Adults with Cancer: Workshop Summary.

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LATE AND LONG-TERM SIDE EFFECTS OF TREATMENT

Studies show that, because of their cancer treatments, many AYA cancer survivors are more likely to develop various chronic health problems than their peers without cancer. Many of these health problems develop long after treatment has ended (see Table 1). Using data collected by its Behavioral Risk Factor System, the CDC found that, compared to people who have never had cancer, AYA cancer survivors have about double the prevalence of cardiovascular disease and are also at increased risk for diabetes, asthma, and hypertension. Furthermore, the prevalence of disability was twice as high in AYA cancer survivors as among those without cancer. Twenty-four percent of AYA cancer survivors reported having had 14 or more days of poor physical health in the previous month, which was double that seen among people without cancer.

TABLE 1. Potential Late Effects of Cancer Treatment, by System and Exposure.

TABLE 1

Potential Late Effects of Cancer Treatment, by System and Exposure.

The Childhood Cancer Survivor Study (CCSS) found that the age at diagnosis does not predict the degree of health conditions developed by a cancer survivor, reported Kevin Oeffinger, director of the Adult Long-Term Follow-Up Program in the Department of Pediatrics at Memorial Sloan-Kettering Cancer Center. This study found that almost half of childhood cancer survivors experience a serious or life-threatening condition or death between 5 and 30 years after diagnosis and that almost three-quarters develop at least one chronic condition (Oeffinger et al., 2006). Another study of adult survivors of childhood cancers found that by age 45, 96 percent of them had developed a chronic health condition and 81 percent had a severe or life-threatening condition, Oeffinger said (Hudson et al., 2013). The risk of developing a health condition increased over time.

Metabolic syndrome and cardiovascular disease are two common late effects of cancer treatment. Compared to healthy controls, survivors of testicular cancer are twice as likely to develop metabolic syndrome, even among those who are still relatively young men, Oeffinger reported. Studies suggest that the increased risk might stem from having received cisplatin and bleomycin chemotherapy, which can damage the lining of blood vessels and start an inflammatory reaction that results in cardiovascular disease. Patients who have had brain tumors also have metabolic disturbances that increase their risk of both cardiac disease and strokes. Cardiac disease risk is also increased in patients who have been treated with anthracyclines, such as doxorubicin. According to Oeffinger, almost all women who undergo total body irradiation prior to a stem cell transplant during adolescence or the young adult years will develop metabolic syndrome and have a higher risk of developing heart disease, despite often being thin. These women often lose their subcutaneous fat but have increased visceral fat.

Bernard Fuemmeler, associate professor of community and family medicine, psychiatry and behavioral science, and psychology and neuroscience at the Duke University Medical Center, also reported on studies that showed survivors of childhood cancers, especially those with leukemia, or those treated with high-dose radiation, were more likely to be obese (Meacham et al., 2005; Oeffinger et al., 2003; Tai et al., 2012). The CCSS found that having cranial radiation therapy, being diagnosed at a younger age, or being female boosted the risk of developing obesity. One study of children with ALL found that 23 percent were obese by the end of their treatment, compared to 14 percent who were obese at diagnosis (Withycombe et al., 2009). Another study found that male survivors of childhood cancers had body mass indices similar to those of their siblings but that they had greater trunk fat and total body fat (Miller et al., 2010). “These studies cause concern that during that year of treatment, children are not being as active as they usually are and so are losing the opportunity to gain lean muscle mass,” Fuemmeler said. Unfortunately, there are few data regarding these late effects among survivors of AYA cancer.

Cancer survivors are also at risk for secondary malignancies (see Table 1). Survivors of Hodgkin's lymphoma (HL) have a particularly high risk of developing another cancer, Hayes-Lattin said. A study by Hodgson (2011) found that the risk of developing another malignancy increased by more than 1 percent per year (see Figure 3). The risk varied depending on what age the HL diagnosis was made. “Although many of our Hodgkin's lymphoma patients have little morbidity at the end of their treatment, about 16 percent that we follow have gone on to develop three or more major primary cancers,” Oeffinger said. Because of that, oncologists are now frequently opting to treat HL patients with a chemotherapy that goes by the acronym ABVD (containing adriamycin, bleomycin, vinblastin, and dacarbazine) instead of an older chemotherapy regimen called MOPP (containing mustragen, oncovin [aka vincristine], procarbazine, and prednisone) because the former has a reduced risk of morbidity and late effects.

FIGURE 3. Cumulative incidence of solid cancers among 5-year survivors of Hodgkin's lymphoma (HL) compared with controls of the same age in the general population (GP).

FIGURE 3

Cumulative incidence of solid cancers among 5-year survivors of Hodgkin's lymphoma (HL) compared with controls of the same age in the general population (GP). NOTE: A = males, B = females. SOURCES: Hayes-Lattin Presentation; Hodgson et al.: Journal of (more...)

Breast cancer is particularly prevalent among survivors of childhood HL who were treated with chest radiation. One study found that 35 percent of women with HL who received chest radiation developed breast cancer by age 50, compared to 31 percent of women with mutations in the BRCA genes and 4 percent of controls. The younger the women were when they received the radiation therapy and the higher the dose of radiation they received, the more likely they were to develop breast cancer. Risk tapers off in those who were 35 years or older when they received the treatment. The interval between chest radiation and the development of breast cancer is usually between 10 and 20 years. Bilateral breast cancer is also more common in women who received chest radiation. “It is overwhelming how frequently we see bilateral disease, and we need to be very proactive with that,” said Oeffinger. He added that survival following a breast cancer diagnosis is linked to the stage of the cancer at diagnosis, just as it would be for someone without a prior cancer diagnosis, and that the hormone receptor status of the breast tumors in HL survivors is similar to that among the general population. By contrast, radiation to the ovaries lowers breast cancer risk, presumably by lowering estrogen exposure.

Copyright 2013 by the National Academy of Sciences. All rights reserved.
Bookshelf ID: NBK179861

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