Physical Outcomes of Long Term Survivors

Although the immediate toxicity of intensive chemotherapy, steroids, antibiotics, and radiation has been evident from the start, the long-term impact has only gradually become apparent. The term late effects is used to refer to the medical problems that can be traced to cancer treatment but that do not become apparent until 5-10 years later (Nunez et al. 2007). Long-term follow-up of childhood cancer survivors has led to an understanding of the potential problems associated with specific treatments. In some cases, the treatment has been modified in response to these findings. For example, because intensive radiation to the central nervous system in early childhood was found to be associated with significant learning disabilities later, oncologists worked to see how little radiation could be used and still be effective. Intrathecal methotrexate is now often used instead of cranial irradiation, with a signif icant decrease in cognitive impairment (Spiegler et al. 2006).

The Children's Oncology Group (2008) document titled "Long-Term Follow-Up Guidelines for Survivors of Childhood, Adolescent, and Young Adult Cancers" details the specific problems that have been seen following treatments with radiation, heavy metals, antimetabolites, alkylating agents, antitumor antibiotics, corticosteroids, anthracycline antibiotics, enzymes, plant alkaloids, and epipo-dophyllotoxins. The guide addresses the potential damage to each organ system and the follow-up needed. Treatments may affect the eye, ear, neuroendocrine system, oral cavity, thyroid, breast, heart, lungs, spleen, liver, gastrointestinal system, muscu-loskeletal system, urinary tract, and reproductive system.

The following are examples of common long-term problems associated with cancer treatment that can have psychological or functional impact:

• Altered bone metabolism, resulting in earlier onset of osteopenia and osteoporosis (Wasilewski-Masker et al. 2008)

• Cardiotoxicity and cardiovascular damage, resulting in a dilated cardiomyopathy or early onset of cardiovascular disease (Ruggiero et al. 2008)

• Endocrine problems, such as hypothyroidism and growth factor deficiency (Stava et al. 2007)

• Significant deficits in attention, and smaller white matter volumes in the brain (Reddick et al. 2006)

Hearing loss, resulting in learning problems (Gurney et al. 2007; Notteghem et al. 2003)

The Childhood Cancer Survivor Study has provided the most detailed information on the long-term impact of pediatric cancer and its treatment. Six health domains were assessed in 9,535 young adults diagnosed with childhood cancer between 1970 and 1986 and compared with those in 2,916 randomly selected siblings of the survivors. Compared with siblings, survivors reported poorer general health (odds ratio [OR]: 2.5), mental health (OR: 1.8), activity limitations (OR: 2.7), and functional impairment (OR: 5.2) (Hudson et al. 2003). The 15-year cumulative incidence of second malignancies or late mortality did not differ between racial or ethnic groups. However, survivors who self-identified as black or Hispanic were more likely than white survivors to be of lower socioeconomic status, and black survivors were less likely than white or Hispanic survivors to report adverse mental health, smoking, or drinking and more likely than white or Hispanic survivors to report use of preventive health care (Castellino et al. 2005).

Given the multiple physical problems experienced by survivors, researchers questioned how much these medical sequelae impact survivors' function and quality of life. Health-related quality of life (HRQOL) and life satisfaction were compared for 7,147 of the young adult participants from the Childhood Cancer Survivor Study and 388 siblings. Both survivors and siblings reported fewer symptoms of global distress than population norms, and most survivors reported present and predicted future life satisfaction (Zeltzer et al. 2008). Evaluation of HRQOL in survivors of Wilms' tumor and neuroblastoma found that these survivors did not differ from population norms on any component of the HRQOL other than the mental component (Nathan et al. 2007).

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