Temporal patterns in the risk of chronic health conditions in survivors of childhood cancer diagnosed 1970-99: a report from the Childhood Cancer Survivor Study cohort.
Ontology highlight
ABSTRACT:
SUBMITTER: Gibson TM
PROVIDER: S-EPMC6309183 | biostudies-literature | 2018 Dec
REPOSITORIES: biostudies-literature
Publications
Temporal patterns in the risk of chronic health conditions in survivors of childhood cancer diagnosed 1970-99: a report from the Childhood Cancer Survivor Study cohort.
Gibson Todd M TM Mostoufi-Moab Sogol S Stratton Kayla L KL Leisenring Wendy M WM Barnea Dana D Chow Eric J EJ Donaldson Sarah S SS Howell Rebecca M RM Hudson Melissa M MM Mahajan Anita A Nathan Paul C PC Ness Kirsten K KK Sklar Charles A CA Tonorezos Emily S ES Weldon Christopher B CB Wells Elizabeth M EM Yasui Yutaka Y Armstrong Gregory T GT Robison Leslie L LL Oeffinger Kevin C KC
The Lancet. Oncology 20181108 12
<h4>Background</h4>Treatments for childhood cancer have evolved over the past 50 years, with the goal of maximising the proportion of patients who achieve long-term survival, while minimising the adverse effects of therapy. We aimed to assess incidence patterns of serious chronic health conditions in long-term survivors of childhood cancer across three decades of diagnosis and treatment.<h4>Methods</h4>We used data from the Childhood Cancer Survivor Study, a retrospective cohort with longitudina ...[more]
Similar Datasets
Project description:OBJECTIVE:To investigate the impact of modifications to contemporary cancer protocols, which minimize exposures to cardiotoxic treatments and preserve long term health, on serious cardiac outcomes among adult survivors of childhood cancer. DESIGN:Retrospective cohort study. SETTING:27 institutions participating in the Childhood Cancer Survivor Study. PARTICIPANTS:23?462 five year survivors (6193 (26.4%) treated in the 1970s, 9363 (39.9%) treated in the 1980s, and 7906 (33.6%) treated in the 1990s) of leukemia, brain cancer, Hodgkin lymphoma, non-Hodgkin lymphoma, renal tumors, neuroblastoma, soft tissue sarcomas, and bone sarcomas diagnosed prior to age 21 years between 1 January 1970 and 31 December 1999. Median age at diagnosis was 6.1 years (range 0-20.9) and 27.7 years (8.2-58.3) at last follow-up. A comparison group of 5057 siblings of cancer survivors were also included. MAIN OUTCOME MEASURES:Cumulative incidence and 95% confidence intervals of reported heart failure, coronary artery disease, valvular heart disease, pericardial disease, and arrhythmias by treatment decade. Events were graded according to the National Cancer Institute's Common Terminology Criteria for Adverse Events. Multivariable subdistribution hazard models were used to estimate hazard ratios by decade, and mediation analysis examined risks with and without exposure to cardiotoxic treatments. RESULTS:The 20 year cumulative incidence of heart failure (0.69% for those treated in the 1970s, 0.74% for those treated in the 1980s, 0.54% for those treated in the 1990s) and coronary artery disease (0.38%, 0.24%, 0.19%, respectively), decreased in more recent eras (P<0.01), though not for valvular disease (0.06%, 0.06%, 0.05%), pericardial disease (0.04%, 0.02%, 0.03%), or arrhythmias (0.08%, 0.09%, 0.13%). Compared with survivors with a diagnosis in the 1970s, the risk of heart failure, coronary artery disease, and valvular heart disease decreased in the 1980s and 1990s but only significantly for coronary artery disease (hazard ratio 0.65, 95% confidence interval 0.45 to 0.92 and 0.53, 0.36 to 0.77, respectively). The overall risk of coronary artery disease was attenuated by adjustment for cardiac radiation (0.90, 0.78 to 1.05), particularly among survivors of Hodgkin lymphoma (unadjusted for radiation: 0.77, 0.66 to 0.89; adjusted for radiation: 0.87, 0.69 to 1.10). CONCLUSIONS:Historical reductions in exposure to cardiac radiation have been associated with a reduced risk of coronary artery disease among adult survivors of childhood cancer. Additional follow-up is needed to investigate risk reductions for other cardiac outcomes. TRIAL REGISTRATION:ClinicalTrials.gov NCT01120353.
| S-EPMC7190022 | biostudies-literature
Project description:BackgroundThe effect of many contemporary chemotherapeutic drugs on pregnancy and livebirth is not well established. We aimed to establish the effects of these drugs on pregnancy in male and female survivors of childhood cancer not exposed to pelvic or cranial radiotherapy.MethodsWe used data from a subset of the Childhood Cancer Survivor Study cohort, which followed 5-year survivors of the most common types of childhood cancer who were diagnosed before age 21 years and treated at 27 institutions in the USA and Canada between 1970 and 1999. We extracted doses of 14 alkylating and similar DNA interstrand crosslinking drugs from medical records. We used sex-specific Cox models to establish the independent effects of each drug and the cumulative cyclophosphamide equivalent dose of all drugs in relation to pregnancies and livebirths occurring between ages 15 years and 44 years. We included siblings of survivors as a comparison group.FindingsWe included 10 938 survivors and 3949 siblings. After a median follow-up of 8 years (IQR 4-12) from cohort entry or at age 15 years, whichever was later, 4149 (38%) survivors reported having or siring a pregnancy, of whom 3453 (83%) individuals reported at least one livebirth. After a median follow-up of 10 years (IQR 6-15), 2445 (62%) siblings reported having or siring a pregnancy, of whom 2201 (90%) individuals reported at least one livebirth. In multivariable analysis, survivors had a decreased likelihood of siring or having a pregnancy versus siblings (male survivors: hazard ratio [HR] 0·63, 95% CI 0·58-0·68; p<0·0001; female survivors: 0·87, 0·81-0·94; p<0·0001) or of having a livebirth (male survivors: 0·63, 0·58-0·69; p<0·0001; female survivors: 0·82, 0·76-0·89; p<0·0001). In male survivors, reduced likelihood of pregnancy was associated with upper tertile doses of cyclophosphamide (HR 0·60, 95% CI 0·51-0·71; p<0·0001), ifosfamide (0·42, 0·23-0·79; p=0·0069), procarbazine (0·30, 0·20-0·46; p<0·0001) and cisplatin (0·56, 0·39-0·82; p=0·0023). Cyclophosphamide equivalent dose in male survivors was significantly associated with a decreased likelihood of siring a pregnancy (per 5000 mg/m(2) increments: HR 0·82, 95% CI 0·79-0·86; p<0·0001). However, in female survivors, only busulfan (<450 mg/m(2) HR 0·22, 95% CI 0·06-0·79; p=0·020; ≥450 mg/m(2) 0·14, 0·03-0·55; p=0·0051) and doses of lomustine equal to or greater than 411 mg/m(2) (0·41, 0·17-0·98; p=0·046) were significantly associated with reduced pregnancy; cyclophosphamide equivalent dose was associated with risk only at the highest doses in analyses categorised by quartile (upper quartile vs no exposure: HR 0·85, 95% CI 0·74-0·98; p=0·023). Results for livebirth were similar to those for pregnancy.InterpretationGreater doses of contemporary alkylating drugs and cisplatin were associated with a decreased likelihood of siring a pregnancy in male survivors of childhood cancer. However, our findings should provide reassurance to most female survivors treated with chemotherapy without radiotherapy to the pelvis or brain, given that chemotherapy-specific effects on pregnancy were generally few. Nevertheless, consideration of fertility preservation before cancer treatment remains important to maximise the reproductive potential of all adolescents newly diagnosed with cancer.FundingNational Cancer Institute, National Institutes of Health, and the American Lebanese-Syrian Associated Charities.
| S-EPMC4907859 | biostudies-literature
Project description:BackgroundNeurocognitive impairment in survivors of childhood cancer may be associated with direct neurotoxicity, as well as indirect effects of systemic health complications. We evaluated associations among treatment exposures, chronic health conditions, and neurocognitive outcomes in adult survivors of childhood cancer.MethodsParticipants included 5507 adult survivors of childhood cancer (47.1% male; mean [SD] age = 31.8 [7.6] years at evaluation; 23.1 [4.5] years postdiagnosis) in the Childhood Cancer Survivor Study who completed a self-report measure of neurocognitive function. Cardiac, pulmonary, and endocrine chronic health conditions were graded using the National Cancer Institute Common Terminology Criteria for Adverse Events (version 4.03). Structural equation modeling was used to examine a priori hypothesized causal pathways among cancer treatment, subsequent chronic health conditions, and neurocognitive outcomes. Multivariable models were used to estimate relative risk for associations of treatments and chronic conditions on neurocognitive function. All statistical tests were two-sided.ResultsOne-third of survivors with a grade 2 or higher chronic condition reported impairments in task efficiency and memory. In addition to direct effects of cranial radiation, path analyses and multivariable models demonstrated direct effects of cardiopulmonary (β = 0.10, P = .002; relative risk [RR] = 1.27, 95% confidence interval [CI] = 1.12 to 1.44) and endocrine (β = 0.07, P = .04; RR = 1.14, 95% CI = 1.02 to 1.28) conditions on impaired task efficiency. We identified similar effects of cardiopulmonary condition on memory (P = .01) and emotional regulation (P = .01). Thoracic radiation was associated with impaired task efficiency (P = .01) and emotional regulation (P = .01) through endocrine morbidity.ConclusionsNon-neurotoxic exposures, such as thoracic radiation, can adversely impact survivors' neurocognitive function through chronic conditions. Management of chronic diseases may mitigate neurocognitive outcomes among aging survivors of childhood cancer.
| S-EPMC6059140 | biostudies-literature
Project description:BackgroundStudies have found associations between cancer therapies and auditory complications, but data are limited on long-term outcomes and risks associated with multiple exposures.ProcedureThe Childhood Cancer Survivor Study is a retrospective cohort investigating health outcomes of long-term survivors (5+ years) diagnosed and treated between 1970 and 1986 compared to a randomly selected sibling cohort. Questionnaires were completed by 14,358 survivors of childhood cancer and 4,023 sibling controls. Analysis determined the first occurrence of four auditory conditions in two time periods: diagnosis to 5 years post-diagnosis, and ≥ 5 years post-diagnosis. Multivariable analyses determined the relative risks (RR) and 95% confidence interval (CI) of auditory conditions by treatment exposure.ResultsFive or more years from cancer diagnosis, survivors were at increased risk of problems hearing sounds (RR = 2.3; 95% CI: 1.8-2.8), tinnitus (RR = 1.7; 95% CI: 1.4-2.1), hearing loss requiring an aid (RR = 4.4; 95% CI: 2.8-6.9), and hearing loss in 1 or both ears not corrected by a hearing aid (RR = 5.2; 95% CI: 2.8-9.5), when compared to siblings. Temporal lobe and posterior fossa radiation was associated with these outcomes in a dose-dependent fashion. Exposure to platinum compounds was associated with an increased risk of problems hearing sounds (RR = 2.1; 95% CI: 1.3-3.2), tinnitus (RR = 2.8; 95% CI: 1.9-4.2), and hearing loss requiring an aid (RR = 4.1; 95% CI: 2.5-6.7).ConclusionsChildhood cancer survivors are at risk of developing auditory complications. Radiation and platinum compounds are determinants of this risk. Follow-up is needed to evaluate the impact of auditory conditions on quality of life.
| S-EPMC3091978 | biostudies-literature
Project description:BackgroundAdult childhood cancer survivors report high levels of unemployment, although it is unknown whether this is because of health or employability limitations.ObjectivesWe examined 2 employment outcomes from 2003 in the Childhood Cancer Survivor Study (CCSS): (1) health-related unemployment and (2) unemployed but seeking work. We compared survivors with a nearest-age CCSS sibling cohort and examined demographic and treatment-related risk groups for each outcome.MethodsWe studied 6339 survivors and 1967 siblings ≥25 years of age excluding those unemployed by choice. Multivariable generalized linear models evaluated whether survivors were more likely to be unemployed than siblings and whether certain survivors were at a higher risk for unemployment.ResultsSurvivors (10.4%) reported health-related unemployment more often than siblings (1.8%; Relative Risk [RR], 6.07; 95% Confidence Interval [CI], 4.32-8.53). Survivors (5.7%) were more likely to report being unemployed but seeking work than siblings (2.7%; RR, 1.90; 95% CI, 1.43-2.54). Health-related unemployment was more common in female survivors than males (Odds Ratio [OR], 1.73; 95% CI, 1.43-2.08). Cranial radiotherapy doses ≥25 Gy were associated with higher odds of unemployment (health-related: OR, 3.47; 95% CI, 2.54-4.74; seeking work: OR, 1.77; 95% CI, 1.15-2.71). Unemployed survivors reported higher levels of poor physical functioning than employed survivors, and had lower education and income and were more likely to be publicly insured than unemployed siblings.ConclusionsChildhood cancer survivors have higher levels of unemployment because of health or being between jobs. High-risk survivors may need vocational assistance.
| S-EPMC3428202 | biostudies-literature
Project description:BackgroundSurvivors of childhood central nervous system (CNS) tumors experience high rates of treatment-related neurologic sequelae. Whether survivors continue to be at increased risk for new events as they age is unknown.MethodsAdverse neurologic health conditions in 5-year survivors of CNS tumors from the Childhood Cancer Survivor Study (n = 1876) were evaluated longitudinally at a median 23.0 years from diagnosis (range, 5.1-38.9), median age at last evaluation 30.3 years (range, 6.1-56.4). Multivariable regression estimated hazard ratios (HRs) and 95% CIs.ResultsFrom 5 to 30 years post diagnosis, cumulative incidence increased for seizures from 27% to 41%, motor impairment 21% to 35%, and hearing loss 9% to 23%. Risks were elevated compared with siblings (eg, seizures HR: 12.7; 95% CI: 9.6-16.7; motor impairment HR: 7.6; 95% CI: 5.8-9.9; hearing loss HR: 18.4; 95% CI: 13.1-25.9). Regional brain doses of radiation therapy were associated with development of new deficits (eg, frontal ?50 Gy and motor impairment HR: 2.0; 95% CI: 1.2-3.4). Increased risk for motor impairment was also associated with tumor recurrence (HR: 2.6; 95% CI: 1.8-3.8), development of a meningioma (HR: 2.3; 95% CI: 0.9-5.4), and stroke (HR: 14.9; 95% CI: 10.4-21.4). Seizure risk was doubled by recurrence (HR: 2.3; 95% CI: 1.6-3.2), meningioma (HR: 2.6; 95% CI: 1.1-6.5), and stroke (HR: 2.0; 95% CI: 1.1-3.4).ConclusionsCNS tumor survivors remain at risk for new-onset adverse neurologic events across their lifespans at a rate greater than siblings. Cranial radiation, stroke, tumor recurrence, and development of meningioma were independently associated with late-onset adverse neurologic sequelae.
| S-EPMC5761581 | biostudies-literature
Project description:With survival rates higher than 80%, the number of survivors from pediatric cancer continues to increase. Late effects resulting from cancer and cancer therapy are being characterized, but little information exists on sexual health for men who have survived childhood cancer.To assess erectile dysfunction (ED) in men who survived childhood and adolescent cancers and to identify potential risk factors for ED.In total, 1,622 men and 271 eligible brothers in the Childhood Cancer Survivor Study cohort completed the Male Health Questionnaire, which provided information on sexual practices and sexual function. Combined with demographic, cancer, and treatment information from medical record abstraction, results of the Male Health Questionnaire were analyzed using multivariable modeling. The International Index of Erectile Function was used to identify ED in subjects.International Index of Erectile Function.Survivors (mean age = 37.4 years, SD = 7.3 years) reported significantly lower sexual activity in the year before the survey than the brothers (mean age = 38.8 years, SD = 8.5 years) without cancer. ED was reported by 12.3% (95% CI = 10.4-14.3) of survivors and 4.2% (95% CI = 2.0-7.9) of brothers. Survivors showed significantly higher relative risk (RR) for ED (RR = 2.63, 95% CI = 1.40-4.97). In addition to older age, survivors who were exposed to higher-dose (?10 Gy) testicular radiation (RR = 3.55, 95% CI = 1.53-8.24), had surgery on the spinal cord or nerves (RR = 2.87, 95% CI = 1.36-6.05), prostate surgery (RR = 6.56, 95% CI = 3.84-11.20), or pelvic surgery (RR = 2.28, 95% CI = 1.04-4.98) were at higher risk for ED.Men who have survived childhood cancer have a greater than 2.6-fold increased risk for ED and certain cancer-specific treatments are associated with increased risk. Attention to sexual health, with its physical and emotional implications, and opportunities for early detection and intervention in these individuals could be important.
| S-EPMC4879056 | biostudies-literature
Project description:Approximately 80% of children currently survive 5 years following diagnosis of their cancer. Studies based on limited data have implicated certain cancer therapies in the development of ocular sequelae in these survivors.The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study investigating health outcomes of 5+ year survivors diagnosed and treated between 1970 and 1986 compared to a sibling cohort. The baseline questionnaire included questions about the first occurrence of six ocular conditions. Relative risks (RR) and 95% confidence intervals (CI) were calculated from responses of 14,362 survivors and 3,901 siblings.Five or more years from the diagnosis, survivors were at increased risk of cataracts (RR: 10.8; 95% CI: 6.2-18.9), glaucoma (RR: 2.5; 95% CI: 1.1-5.7), legal blindness (RR: 2.6; 95% CI: 1.7-4.0), double vision (RR: 4.1; 95% CI: 2.7-6.1), and dry eyes (RR: 1.9; 95% CI: 1.6-2.4), when compared to siblings. Dose of radiation to the eye was significantly associated with risk of cataracts, legal blindness, double vision, and dry eyes, in a dose-dependent manner. Risk of cataracts were also associated with radiation 3,000+ cGy to the posterior fossa (RR: 8.4; 95% CI: 5.0-14.3), temporal lobe (RR: 9.4; 95% CI: 5.6-15.6), and exposure to prednisone (RR: 2.3; 95% CI: 1.6-3.4).Childhood cancer survivors are at risk of developing late occurring ocular complications, with exposure to glucocorticoids and cranial radiation being important determinants of increased risk. Long-term follow-up is needed to evaluate potential progression of ocular deficits and impact on quality of life.
| S-EPMC2783513 | biostudies-literature
Project description:PURPOSE:To describe and compare the prevalence of mental health access, preference, and use among pediatric cancer survivors and their siblings. To identify factors associated with mental health access and use among survivors. METHODS:Six hundred ninety-eight survivors in the Childhood Cancer Survivor Study (median age?=?39.4; median years from diagnosis?=?30.8) and 210 siblings (median age?=?40.4) were surveyed. Outcomes included having mental health insurance coverage, delaying care due to cost, perceived value of mental health benefits, and visiting a mental health provider in the past year. RESULTS:There were no differences in mental health access, preferences, and use between survivors and siblings (p?>?0.05). Among respondents with a history of distress, most reported not having seen a mental health provider in the past year (80.9% survivors vs. 77.1% siblings; p?=?0.60). Uninsured survivors were more likely to defer mental health services due to cost (24.6 vs. 8.4%; p?<?0.001). In multivariable models, males (OR?=?2.96) and survivors with public (OR?=?6.61) or employer-sponsored insurance (ESI; OR?=?14.37) were more likely to have mental health coverage. CONCLUSIONS:Most childhood cancer survivors value having mental healthcare benefits; however, coverage and use of mental health services remain suboptimal. The most vulnerable of survivors, specifically the uninsured and those with a history of distress, are at risk of experiencing challenges accessing mental health care. IMPLICATIONS FOR CANCER SURVIVORS:Childhood cancer survivors are at risk for experiencing high levels of daily life stress that is compounded by treatment-related sequelae. Integrative, system-based approaches that incorporate financial programs with patient education about insurance benefits can help reduce some of the financial barriers survivors face.
| S-EPMC6054538 | biostudies-literature
Project description:BackgroundGonadotoxic treatment-related infertility has a significant impact on quality of life in childhood cancer survivors. Genome-wide association analyses to delineate the risk of infertility in childhood cancer survivors have not been previously reported.MethodsLeveraging genotype data from a large survivor cohort, the Childhood Cancer Survivor Study (CCSS), we investigated the role of SNPs on future pregnancy or siring a pregnancy in survivors without pelvic, testicular, or brain radiation who had ever been married. We calculated sex-stratified hazard ratios, using Cox proportional hazards modeling, adjusting for birth cohort (before 1965 vs. 1965 or later) and doses of relevant chemotherapies; replication was attempted in the independent St. Jude Lifetime Cohort study (SJLIFE).ResultsIn the CCSS cohort, nine SNPs were found to be suggestive (P < 10-7) or statistically significantly (P < 5 × 10-8) associated with pregnancy, however, none of the SNPs were replicated in SJLIFE. Cohorts differed based on the overall pregnancy rate, frequency of sterilizing procedures, and birth cohort.ConclusionsWe were not able to replicate our findings of SNPs associated with pregnancy in childhood cancer survivors.ImpactFuture attempts at replication should be considered in cohorts treated in a comparable era. In addition, understanding the role of genetics in fertility in childhood cancer survivors may be better approached using more advanced sequencing techniques.
| S-EPMC9444932 | biostudies-literature