Cause of mortality in 5-year survivors of childhood cancer
Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, USA. Pediatric Blood & Cancer
(Impact Factor: 2.39).
06/2007; 48(7):723-6. DOI: 10.1002/pbc.21114
Survivors of childhood and adolescent cancer are at risk for long-term effects of disease and treatment. The Childhood Cancer Survivor Study assessed overall and cause-specific mortality in a retrospective cohort of 20,690 5-year survivors. Eligible subjects were individuals diagnosed with cancer (from 1970 to 1986) before the age of 21 who had survived 5 years from diagnosis. Underlying cause of death was obtained from death certificates and other sources, then and coded and categorized as recurrent disease, sequel of cancer treatment, or non-cancer-related. Age and sex standardized mortality ratios (SMRs) were calculated using United States population mortality data. The cohort demonstrated an 8.2-fold excess in overall mortality (95% confidence interval, 7.9 to 8.5). Recurrence of the original cancer was the leading cause of death among 5-year survivors, accounting for 57% of deaths. Statistically significant excess mortality rates were seen due to subsequent malignancies (SMR = 15.0), along with cardiac (SMR = 6.9), and pulmonary (SMR = 8.7). There was no increase seen for automotive accidents (SMR = 1.0), other accidents (SMR = 1.3), or suicide (SMR = 1.0). While recurrent disease remains a major contributor to late mortality in 5-year survivors of childhood cancer, significant excesses in mortality risk associated with treatment-related complications exist up to 25 years after the initial cancer diagnosis.
Available from: Berta Jereb
- "Late sequelae evaluations. The period between the diagnosis and the follow-up evaluation (left-hand side, a) and the percentage of patients with different evaluation scores from Table 2 (right-hand side, b), for the first follow-up evaluation after treatment, the second one performed in December , and the third one in December 2010. "
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ABSTRACT: This is a long-term follow-up clinical study of adolescents and adults, survivors of childhood cancer. We evaluate and analyze the late somatic sequelae of childhood cancer treatment. Many such studies are susceptible to a strong selection bias, i.e., they employ a limited non-systematic sample of patients, based on a clinical hospital that provided the cancer treatment or performed the follow-up. To address the issue of selection bias, we perform here an analysis of late sequelae on a systematic database of the entire population of the children treated for cancer in Slovenia. Due to the specifics of cancer treatment procedures in Slovenia, they have all been treated and followed-up in the same clinic.
The data are based on the centralized registry of cancer patients in Slovenia and present a controlled and homogeneous collection. Late sequelae are evaluated following a modified CTCAE, i.e., the National Cancer Institute's Common Terminology Criteria for Adverse Events version 3.0. We use survival analysis method to estimate the incidence of and risk for late sequelae, where the time variable is measured in years from the diagnosis date, while we follow the event of incidence of late sequelae scored other than none. Survival analysis is performed using KaplanMeier estimator and Cox regression model.
The incidence of mild, moderate, or severe late sequelae of childhood cancer treatment significantly decreased from 75% in the group of patients diagnosed before 1975 to 55% for those diagnosed after 1995. The Cox regression analysis of the risk factors for the incidence of late sequelae identifies three significant factors: treatment modalities, age at diagnosis, and primary diagnosis.
The change of treatment modalities in terms of replacement of surgery and radiotherapy with chemotherapy is the main reason for the decrease of the incidence and the risk for late sequelae of childhood cancer treatment; treatment modalities including surgery significantly increase the risk ratio of late sequelae, while those based on chemotherapy only significantly decreases the risk. Risk of late sequelae increases with the diagnosis age: younger children are more susceptible to late effects of treatment. Finally, primary diagnosis significantly influences the risk for late sequelae, but mostly due to the dependency of the treatment modality on the primary diagnosis.
BMC Research Notes 05/2012; 5:254. DOI:10.1186/1756-0500-5-254
Available from: Joyce E Ohm
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ABSTRACT: Epigenetic gene silencing, and associated promoter CpG island DNA hypermethylation, is an alternative mechanism to mutations by which tumor suppressor genes may be inactivated within a cancer cell. These epigenetic changes are prevalent in all types of cancer, and their appearance may precede genetic changes in premalignant cells and foster the accumulation of additional genetic and epigenetic hits. These epigenetically modified genes constitute important categories of tumor suppressor genes including cell cycle regulators, pro-differentiation factors, and anti-apoptotic genes, and many of these genes are known to play a role in normal development. While the silencing of these genes may play an essential role in tumor initiation or progression, the mechanisms underlying the specific targeting of these genes for DNA hypermethylation remains to be determined. The large numbers of epigenetically silenced genes that may be present in any given tumor, and the clustering of silenced genes within single cell pathways, begs the question of whether gene silencing is a series of random events resulting in an enhanced survival of a premalignant clone, or whether silencing is the result of a directed, instructive program for silencing initiation reflective of the cells of origin for tumors. In this regard, the current review stresses the latter hypothesis and the important possibility that the program is linked, at least for silencing of some cancer genes, to the epigenetic control of stem/precursor cell gene expression patterns.
Cell cycle (Georgetown, Tex.) 06/2007; 6(9):1040-3. DOI:10.1007/978-1-60327-933-8_7 · 4.57 Impact Factor
Available from: Kirsten K Ness
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ABSTRACT: Children with acute lymphoblastic leukemia (ALL), the most common pediatric malignancy, have a 5-year survival rate of better than 80%. Long-term survivors of childhood ALL, however, carry an elevated risk of early mortality from cardiac events and stroke and a disproportionately high prevalence of dyslipidemia and obesity, presumably as an adverse effect of treatment.
As part of a clinical follow-up study of 70 young adult survivors of childhood ALL, we evaluated the degree to which this high-risk group differed in knowledge about symptoms of heart attack and stroke from that of a population-based comparison group frequency-matched by age, sex, and body mass index. Questions from the Behavioral Risk Factor Surveillance System were used to assess health knowledge.
Survivors of ALL scored considerably worse on symptom knowledge than did their population counterparts. The strongest association was observed for chest pain as a symptom of heart attack: ALL survivors were 14-fold more likely than the comparison group to answer the question incorrectly. Seventy-seven percent of survivors failed to identify pain in the jaw, neck, or back as a heart attack symptom.
These results indicate an important gap in knowledge and underscore the need for health education among survivors of childhood leukemia that includes information about symptoms of myocardial infarction and stroke.
Annals of Epidemiology 11/2007; 17(10):778-81. DOI:10.1016/j.annepidem.2007.05.004 · 2.00 Impact Factor
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