Medical Assessment of Adverse Health Outcomes in Long-term Survivors of Childhood Cancer

University of Amsterdam, Amsterdamo, North Holland, Netherlands
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 07/2007; 297(24):2705-15. DOI: 10.1001/jama.297.24.2705
Source: PubMed


Improved survival of children with cancer has been accompanied by multiple treatment-related complications. However, most studies in survivors of childhood cancer focused on only 1 late effect.
To assess the total burden of adverse health outcomes (clinical or subclinical disorders ["adverse events"]) following childhood cancer in a large cohort of childhood cancer survivors with long-term and complete medical follow-up.
Retrospective cohort study of 1362 five-year survivors of childhood cancer treated in a single institution in the Netherlands between 1966 and 1996. All survivors were invited to a late-effects clinic for medical assessment of adverse events. Adverse events occurring before January 2004 were graded for severity in a standardized manner.
Treatment-specific prevalence of adverse events (according to severity) at end of follow-up and relative risk of high or severe burden of disease (> or =2 severe or > or =1 life-threatening or disabling adverse events) associated with various treatments.
Medical follow-up was complete for 94.3% of survivors (median follow-up, 17.0 years). The median attained age at end of follow-up was 24.4 years. Almost 75% of survivors had 1 or more adverse events, and 24.6% had 5 or more adverse events. Furthermore, 40% of survivors had at least 1 severe or life-threatening or disabling adverse event. A high or severe burden of adverse events was observed in 55% of survivors who received radiotherapy only and 15% of survivors treated with chemotherapy only, compared with 25% of survivors who had surgery only (adjusted relative risks, 2.18 [95% confidence interval, 1.62-2.95] and 0.65 [95% confidence interval, 0.46-0.90], respectively). A high or severe burden of adverse events was most often observed in survivors of bone tumors (64%) and least often in survivors of leukemia or Wilms tumor (12% each).
In young adulthood, a substantial proportion of childhood cancer survivors already has a high or severe burden of disease, particularly after radiotherapy. This underscores the need for lifelong risk-stratified medical surveillance of childhood cancer survivors.

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Available from: Richard C Heinen, Sep 30, 2015
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    • "Regrettably, 40% of childhood cancer survivors suffer severe lifethreatening or permanently disabling adverse drug reactions [4]. "
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    ABSTRACT: Objective: Cisplatin is widely used to treat a variety of pediatric solid tumors. One of the most severe and debilitating adverse drug reactions experienced by patients who receive cisplatin therapy is permanent bilateral hearing loss. The aim of this study was to evaluate the incidence and risk factors for cisplatin-induced hearing loss in Mexican pediatric patients. Methods: Detailed medical and drug histories, including use of cisplatin as well as other drugs known to cause hearing loss, were collected from patient medical records. Results of audiology tests on pediatric patients with solid tumors were collected at baseline, during treatment and at the end of cisplatin chemotherapy. Hearing loss was classified according to the Common Terminology Criteria for Adverse Events. Bivariate and multivariate analyses were performed using survival curves. Results: Fifty-nine pediatric patients, median age 11 years (range, 3-17 years) were included in the study. The incidence of cisplatin-induced hearing loss was 56%. Individual risk factors including age (< 5 years), male sex, and concomitant medications were not associated with an increased risk of cisplatin-induced hearing loss. Patients with a diagnosis of osteosarcoma and a cumulative cisplatin dose greater than 400 mg/m(2) were at higher risk of hearing loss compared with all other tumor and cumulative dose combinations (HR = 2.47 [95% CI, 1.043-5.831]). Conclusions: Cumulative dose and tumor type are associated with an increased risk of cisplatin-induced hearing loss. Further research is required to characterize fully the interindividual variation in hearing loss in Mexican patients.
    International Journal of Pediatric Otorhinolaryngology 06/2014; 78(9). DOI:10.1016/j.ijporl.2014.06.007 · 1.19 Impact Factor
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    • "These mechanisms are used when we perform such activities as purposefully paying attention, planning, organizing, forecasting, strategizing, abstracting, drawing analogies, and trying to overcome routinized behaviors (Bishop et al. 2004; Fernandez-Duque et al. 2000). They also enable us to carry out goal-directed behavior and to reflect on and inhibit inappropriate actions (Geenen et al. 2007; Norman and Shallice 1986; Shallice et al. 1994). "
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    • "Significantly improved results of anticancer treatment in children have led to an increased number of survivors. However, available data show that up to 40% of these children suffer from serious late complications, including heart failure, neurotoxicity, nephrotoxicity, growth impairment, hormonal disorders, and secondary cancers [1]. Late complications not only seriously impair the patients' quality of life and cause higher rates of hospitalization, but in 15% of cases, they become the direct cause of the patient's death [2] [3]. "
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    ABSTRACT: Novel markers of nephrotoxicity, including kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18), and beta-2 microglobulin, were used in the detection of acute renal injury. The aim of the study was to establish the frequency of postchemotherapy chronic kidney dysfunction in children and to assess the efficacy of IL-18, KIM-1, and beta-2 microglobulin in the detection of chronic nephropathy. We examined eighty-five patients after chemotherapy (median age of twelve years). The median age at the point of diagnosis was 4.2 years, and the median follow-up time was 4.6 years. We performed classic laboratory tests assessing kidney function and compared the results with novel markers (KIM-1, beta-2 microglobulin, and IL-18). Features of subclinical renal injury were identified in forty-eight children (56.3% of the examined group). Nephropathy, especially tubulopathy, appeared more frequently in patients treated with ifosfamide, cisplatin, and/or carboplatin, following nephrectomy or abdominal radiotherapy (P = 0.14, P = 0.11, and P = 0.08, resp.). Concentrations of IL-18 and beta-2 microglobulin were comparable with classic signs of tubulopathy (P = 0.0001 and P = 0.05). Concentrations of IL-18 were also significantly higher in children treated with highly nephrotoxic drugs (P = 0.0004) following nephrectomy (P = 0.0007) and abdominal radiotherapy (P = 0.01). Concentrations of beta-2 microglobulin were higher after highly toxic chemotherapy (P = 0.004) and after radiotherapy (P = 0.02). ROC curves created utilizing IL-18 data allowed us to distinguish between children with nephropathy (value 28.8 pg/mL) and tubulopathy (37.1 pg/mL). Beta-2 microglobulin and IL-18 seem to be promising markers of chronic renal injury in children after chemotherapy.
    Disease markers 11/2013; 35(6):811-8. DOI:10.1155/2013/369784 · 1.56 Impact Factor
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