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Impact of Cancer Therapy-Related Exposures on Late Mortality in Childhood Cancer Survivors.

ABSTRACT: Survival of children and adolescents diagnosed with cancer has improved dramatically in recent decades, but the substantial burden of late morbidity and mortality (i.e., more than 5 years after cancer diagnosis) associated with pediatric cancer treatments is increasingly being recognized. Progression or recurrence of the initial cancer is a primary cause of death in the initial postdiagnosis period, but as survivors age, there is a dramatic shift in the cause-specific mortality profile. By 15 years postdiagnosis, the death rate attributable to health-related causes other than recurrence or external causes (e.g., accidents, suicide, assault) exceeds that due to primary disease, and by 30 years, these causes account for the largest proportion of cumulative mortality. The two most prominent causes of treatment-related mortality in childhood cancer survivors are subsequent malignant neoplasms and cardiovascular problems, the incidence of which can be largely attributed to the long-term toxicities of radiation and chemotherapy exposures. These late effects of treatment are likely to increase in importance as survivors continue to age, inspiring continued research to better understand their etiology and to inform early detection or prevention efforts.

SUBMITTER: Gibson TM

PROVIDER: S-EPMC4474782 | biostudies-literature | 2015 Jan

REPOSITORIES: biostudies-literature

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Impact of Cancer Therapy-Related Exposures on Late Mortality in Childhood Cancer Survivors.

Gibson Todd M TM Robison Leslie L LL

Chemical research in toxicology 20141219 1

Survival of children and adolescents diagnosed with cancer has improved dramatically in recent decades, but the substantial burden of late morbidity and mortality (i.e., more than 5 years after cancer diagnosis) associated with pediatric cancer treatments is increasingly being recognized. Progression or recurrence of the initial cancer is a primary cause of death in the initial postdiagnosis period, but as survivors age, there is a dramatic shift in the cause-specific mortality profile. By 15 ye ...[more]

PMID: 25474125

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Project description:Among patients in whom childhood cancer was diagnosed in the 1970s and 1980s, 18% of those who survived for 5 years died within the subsequent 25 years. In recent decades, cancer treatments have been modified with the goal of reducing life-threatening late effects.We evaluated late mortality among 34,033 patients in the Childhood Cancer Survivor Study cohort who survived at least 5 years after childhood cancer (i.e., cancer diagnosed before the age of 21 years) for which treatment was initiated during the period from 1970 through 1999. The median follow-up was 21 years (range, 5 to 38). We evaluated demographic and disease factors that were associated with death from health-related causes (i.e., conditions that exclude recurrence or progression of the original cancer and external causes but include the late effects of cancer therapy) using cumulative incidence and piecewise exponential models to estimate relative rates and 95% confidence intervals.Of the 3958 deaths that occurred during the study period, 1618 (41%) were attributable to health-related causes, including 746 deaths from subsequent neoplasms, 241 from cardiac causes, 137 from pulmonary causes, and 494 from other causes. A reduction in 15-year mortality was observed for death from any cause (from 12.4% in the early 1970s to 6.0% in the 1990s, P<0.001 for trend) and from health-related causes (from 3.5% to 2.1%, P<0.001 for trend). These reductions were attributable to decreases in the rates of death from subsequent neoplasm (P<0.001), cardiac causes (P<0.001), and pulmonary causes (P=0.04). Changes in therapy according to decade included reduced rates of cranial radiotherapy for acute lymphoblastic leukemia (85% in the 1970s, 51% in the 1980s, and 19% in the 1990s), of abdominal radiotherapy for Wilms' tumor (78%, 53%, and 43%, respectively), of chest radiotherapy for Hodgkin's lymphoma (87%, 79%, and 61%, respectively), and of anthracycline exposure. Reduction in treatment exposure was associated with reduced late mortality among survivors of acute lymphoblastic leukemia and Wilms' tumor.The strategy of lowering therapeutic exposure has contributed to an observed decline in late mortality among 5-year survivors of childhood cancer. (Funded by the National Cancer Institute and the American Lebanese-Syrian Associated Charities.).

Project description:BackgroundThe proportion of pediatric and adolescent cancer patients surviving 5 years has increased during the past four decades. This growing population of survivors remains at risk for disease- and treatment-associated late mortality.MethodsA total of 20 483 five-year survivors of childhood and adolescent cancer diagnosed between January 1, 1970, and December 31, 1986, and enrolled in the Childhood Cancer Survivor Study (CCSS) were included in a National Death Index search for deaths occurring between January 1, 1979, and December 31, 2002. Treatment information was abstracted from primary medical records. Survival probabilities, standardized mortality ratios (SMRs), and absolute excess risks were calculated for overall and cause-specific deaths. Diagnosis- and sex-specific survival probabilities were estimated by the product-limit method. All statistical tests were two-sided.ResultsAmong the CCSS cohort, 2821 (13.8%) 5-year survivors had died by the end of the follow-up period. The cause of death was obtained for 2534 individuals, with 57.5% of deaths attributed to recurrent disease. Estimated probability of survival 30 years from diagnosis was 82%. When compared with the US population, the absolute excess risk of death from any cause was 7.36 deaths per 1000 person-years. The overall SMR was 8.4 (95% confidence interval [CI] = 8.0 to 8.7). Increases in cause-specific mortality were seen for deaths due to subsequent malignancy (SMR = 15.2, 95% CI = 13.9 to 16.6) and cardiac (SMR = 7.0, 95% CI = 5.9 to 8.2), pulmonary (SMR = 8.8, 95% CI = 6.8 to 11.2), and other medical (SMR = 2.6, 95% CI = 2.3 to 3.0) causes. At 20 years of follow-up (25 years after first cancer diagnosis), the death rate due to a subsequent malignancy exceeded that due to all other causes.ConclusionOur extended follow-up of 5-year survivors of pediatric and adolescent cancer indicates that excess mortality persists long after diagnosis. Continued observation is needed to further define lifetime risk and to determine the potential contribution of chronic health conditions and modifiable health behaviors.

Project description:PurposeSurvivors of childhood cancer carry a substantial burden of long-term morbidity; personal risk awareness is critical to ensure survivors' engagement in early detection/management of complications. The impact of education provided in survivorship clinics on survivors' understanding of their personal health risks is unclear.MethodsPatients diagnosed with cancer at age 21 years or younger and at 2 or more years off therapy completed questionnaires about awareness of personal risk for therapy-related complications at T0 (first survivorship clinic visit) and at T1 to T5 (subsequent visits). After questionnaire completion at each clinic visit, survivors received education tailored to personal risk.ResultsA total of 369 survivors completed 1,248 visits (median, three visits; range, one to six visits). The median age at cancer diagnosis was 11 years (range, 0 to 21 years); the median age at T0 was 24 years (range, 5 to 57 years); 38% were white; 45% had leukemia; and 34% received hematopoietic cell transplantation. The cohort was at risk for a median of six (range, one to nine) complications. Awareness increased from 38.6% at T0 to 66.3% at T3. Generalized estimating equations (that adjusted for diagnosis, hematopoietic cell transplantation, race/ethnicity, and patient/parent education) showed significant gains in awareness from T0 to T1 (P < .001), T1 to T2 (P = .03), and T2 to T3 (P < .001) but no significant gain thereafter through T5 (P = .7). Predictors of low awareness included education less than a college degree (odds ratio [OR], 1.9; P = .02), longer time from diagnosis (OR, 1.03/year; P = .04), diagnosis of leukemia (OR, 2.1; P = .004), nonwhite race (OR, 2.8; P < .001), and risk for six or fewer complications (OR, 2.1; P = .002).ConclusionRisk-based education in a survivorship clinic significantly increases awareness of personal health risk through three sessions, with saturation thereafter. Vulnerable populations with minimal gain in awareness identified in this study could inform targeted interventions.

Project description:BackgroundThe prevalence and associated psychosocial morbidity of late-onset anorectal disease after surgery and radiotherapy for the treatment of childhood cancer are not known.MethodsA total of 25,530 survivors diagnosed between 1970 and 1999 (median age at cancer diagnosis, 6.1 years; age at survey, 30.2 years) and 5036 siblings were evaluated for late-onset anorectal disease, which was defined as a self-reported fistula-in-ano, self-reported anorectal stricture, or pathology- or medical record-confirmed anorectal subsequent malignant neoplasm (SMN) 5 or more years after the primary cancer diagnosis. Piecewise exponential models compared the survivors and siblings and examined associations between cancer treatments and late-onset anorectal disease. Multiple logistic regression with generalized estimating equations was used to evaluate associations between late-onset anorectal disease and emotional distress, as defined by the Brief Symptom Inventory 18 (BSI-18), and health-related quality of life, as defined by the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36).ResultsBy 45 years after the diagnosis, 394 survivors (fistula, n = 291; stricture, n = 116; anorectal SMN, n = 26) and 84 siblings (fistula, n = 73; stricture, n = 23; anorectal neoplasm, n = 1) had developed late-onset anorectal disease (adjusted rate ratio [RR] for survivors vs siblings, 1.2; 95% confidence interval [CI], 1.0-1.5). Among survivors, pelvic radiotherapy with ≥30 Gy within 5 years of the cancer diagnosis was associated with late-onset anorectal disease (adjusted RR for 30-49.9 Gy vs none, 1.6; 95% CI, 1.1-2.3; adjusted RR for ≥50 Gy vs none, 5.4; 95% CI, 3.1-9.2). Late-onset anorectal disease was associated with psychosocial impairment in all BSI-18 and SF-36 domains.ConclusionsLate-onset anorectal disease was more common among childhood cancer survivors who received higher doses of pelvic radiotherapy and was associated with substantial psychosocial morbidity.

Project description:Simple Summary Due to previous cancer and its treatments, long-term childhood cancer survivors (CCS) are at risk of developing medical comorbidities, as well as socioeconomic vulnerability. Above all, work placement, financial independence, and job satisfaction can represent burdensome areas for some CCS. Regarding this topic, it is important to consider the variety of country-specific educational and vocational systems. The aim of this study is to provide a description of the occupational status of CCS in the Italian socio-economic scenery and to evaluate the association between late effects and unemployment and late effects and job satisfaction. Our data contribute to the description of the different country scenery of work placement for CCS in Europe and agree with previous literature on the impact of severe late effects on occupation. Future research in this field can be focused on interventions to improve CCS in obtaining jobs suitable for their health. Abstract Late effects of cancer and its treatments during childhood or adolescence can impact work placement and increase the risk of unemployment. The aim of this study is to describe the work placement and the perceived job and economic satisfaction of long-term childhood cancer survivors (CCS). Jobs have been categorized according to the International Standard Classification of Occupations version 08 (ISCO-08), and satisfaction has been evaluated through the Satisfaction Profile (SAT-P). Out of 240 CCS (female = 98) included: 53 were students, 46 were unemployed and 141 were employed. Within unemployed survivors, 89.13% were affected by late effects (n = 41). The presence of at least one severe late effect was significantly associated with the probability of unemployment (OR 3.21; 95% CI 1.13–9.12, p < 0.050), and having any late effect was inversely related to the level of satisfaction of the financial situation of unemployed CCS (b −35.47; 95% CI −59.19, −11.74, p = 0.004). Our results showed that being a survivor with severe comorbidities has a significantly negative impact on occupation and worsens the perception of satisfaction of economic situations. Routinary follow-up care of CCS should include the surveillance of socioeconomic development and provide interventions, helping them to reach jobs suitable for their health.

Dataset Information

Impact of Cancer Therapy-Related Exposures on Late Mortality in Childhood Cancer Survivors.

Publications

Impact of Cancer Therapy-Related Exposures on Late Mortality in Childhood Cancer Survivors.

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