Challenges After Curative Treatment for Childhood Cancer and Long-Term Follow up of Survivors

Departments of Pediatrics and Medicine, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Hematology/oncology clinics of North America (Impact Factor: 2.3). 02/2010; 24(1):129-49. DOI: 10.1016/j.hoc.2009.11.013
Source: PubMed


Childhood cancer survivors are at increased risk of serious morbidity, premature mortality, and diminished health status. Proactive and anticipatory risk-based health care of survivors and healthy lifestyles can reduce these risks. In this article, the authors first briefly discuss four common problems of survivors: neurocognitive dysfunction, cardiovascular disease, infertility and gonadal dysfunction, and psychosocial problems. Second, the authors discuss the concept of risk-based care, promote the use of recently developed evidence-based guidelines, describe current care in the United States, Canada, and the Netherlands, and articulate a model for shared survivor care that aims to optimize life long health of survivors and improve two-way communication between the cancer center and the primary care physician.

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    • "As of 2005, there were over 328,000 childhood cancer survivors in the USA, a number that will continue to grow with emerging treatment procedures [1]. Unfortunately, survival from childhood cancer is often accompanied by an increased risk for adverse late effects from treatment [2] [3] [4], including cardiovascular risk [5] [6], insulin resistance [7], and neurologic, musculoskeletal, and pulmonary complications [8]. Furthermore, adult survivors of childhood cancer may be particularly prone to weight-related problems as approximately half report low levels of physical activity [9] [10]. "
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    ABSTRACT: Background. Population-based studies are needed to estimate the prevalence of underweight or overweight/obese childhood cancer survivors. Procedure. Adult survivors (diagnosed ≤20 years) were identified from the linked Utah Cancer Registry and Utah Population Database. We included survivors currently aged ≥20 years and ≥5 years from diagnosis (N = 1060), and a comparison cohort selected on birth year and sex (N = 5410). BMI was calculated from driver license data available from 2000 to 2010. Multivariable generalized linear regression models were used to calculate prevalence relative risks (RR) and 95% confidence intervals (95% CI) of BMI outcomes for survivors and the comparison cohort. Results. Average time since diagnosis was 18.5 years (SD = 7.8), and mean age at BMI for both groups was 30.5 (survivors SD = 7.7, comparison SD = 8.0). Considering all diagnoses, survivors were not at higher risk for being underweight or overweight/obese than the comparison. Male central nervous system tumor survivors were overweight (RR = 1.12, 95% CI 1.01-1.23) more often than the comparison. Female survivors, who were diagnosed at age 10 and under, had a 10% higher risk of being obese than survivors diagnosed at ages 16-20 (P < 0.05). Conclusion. While certain groups of childhood cancer survivors are at risk for being overweight/obese, in general they do not differ from population estimates.
    Journal of Cancer Epidemiology 01/2014; 2014:531958. DOI:10.1155/2014/531958
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    • "The majority of children treated for cancer will eventually develop at least one chronic medical condition related to their previous exposure to chemotherapy and/or radiation therapy [1,2]. Identifying a biomarker indicative of global damage level would be useful in predicting individual sensitivity to anti-cancer treatment long-term side effects. "
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    ABSTRACT: Most childhood cancer survivors will develop ionizing radiation treatment-related health conditions that, in many instances, resemble age-associated pathologies. Treatment-induced premature senescence could be an underlying mechanism. Here we wanted to know whether the expression of p16INK4a, a senescence/aging biomarker, is increased in skin biopsies of acute lymphoblastic leukemia survivors (ALL), previously exposed to chemotherapy and radiation therapy. Several years post-treatments, we found p16INK4a mRNA levels are 5.8 times higher in scalp skin biopsies (targeted by cranial irradiation therapy) compared to buttocks skin biopsies (n = 10, p = 0.01). These results demonstrate for the first time that premature senescence is induced in pediatric cancer survivors and that p16INK4a expression could be used as a potential biomarker in this population.
    Radiation Oncology 10/2013; 8(1):252. DOI:10.1186/1748-717X-8-252 · 2.55 Impact Factor
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    • "Although the mechanisms underlying the observed muscle dysfunction are not clear, it is likely that chemotherapy treatments have an important direct role. The growing awareness of the late effects of cancer and cancer treatments has stimulated calls to establish long-term surveillance for the survivors of pediatric cancers (Aslett et al., 2007; Oeffinger et al., 2010; Prasad et al., 2010; Skinner, 2012b). If successful such programs will allow more systematic identification and characterization of affected individuals, and will hopefully facilitate studies to investigate the hypotheses proposed here and to initiate potential intervention studies. "
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    ABSTRACT: There is evidence that survivors of childhood cancers, such as acute lymphoblastic leukemia (ALL), have increased rates of long-term skeletal muscle dysfunction. This places them at higher risk of physical restriction and functional impairment as well as potentially contributing to observed increases in cardiovascular disease and insulin resistance in later life. The mechanisms underlying these changes in skeletal muscle are unknown but chemotherapy drugs used in treatment for ALL are strongly implicated. Normal skeletal muscle growth, development, and function are dependent on correctly functioning muscle satellite cells, muscle motor neurons, and muscle mitochondria. Each of these key components is potentially susceptible to damage by chemotherapy in childhood, particularly prolonged courses including repeated administration of combination chemotherapy. If this chemotherapy-induced damage is not fully reversible, impairment of satellite cells, muscle motor innervation, and mitochondria could, either singly or together, lead to the emergence of delayed or persistent skeletal muscle dysfunction many years later. The known effects of individual drugs used in the treatment of ALL are outlined and the need for specific targeted studies to investigate the mechanisms underlying persistent muscle dysfunction in survivors of ALL and other childhood cancers is highlighted.
    Frontiers in Pharmacology 04/2013; 4:49. DOI:10.3389/fphar.2013.00049 · 3.80 Impact Factor
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