Late Effects in Childhood Cancer Survivors: Early Studies, Survivor Cohorts, and Significant Contributions to the Field of Late Effects.
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ABSTRACT:
SUBMITTER: Norsker FN
PROVIDER: S-EPMC8393933 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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: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.
| S-EPMC2556702 | biostudies-literature
Project description:ObjectiveTo delineate the impact of treatment exposures and chronic health conditions on psychological, educational, and social outcomes in adolescent survivors of Wilms tumor.MethodsParent reports from the Childhood Cancer Survivor Study were analyzed for 666 adolescent survivors of Wilms tumor and 698 adolescent siblings. Adjusting for race and household income, survivors were compared to siblings on the Behavior Problems Index and educational outcomes. Multivariable modified Poisson regression estimated relative risks (RR) for therapeutic exposures and chronic health conditions (CTCAE 4.03 graded) among survivors, adjusting for sex, race, income, and age at diagnosis.ResultsCompared to siblings, adolescent survivors of Wilms tumor were more likely to take psychoactive medication (9.4% vs. 5.1%, p < 0.001) and utilize special education services (25.5% vs. 12.6%, p < 0.001) but did not differ significantly in emotional and behavioral problems. Survivors were less likely to be friendless (7.2% vs. 10.1%, p = 0.04) but were more likely to have difficulty getting along with friends (14.5% vs. 7.8%, p < 0.001). Among survivors, use of special education services was associated with abdomen plus chest radiation (RR = 1.98, CI:1.18-3.34). Those with grade 2-4 cardiovascular conditions had higher risk for anxiety/depression (RR = 1.95, CI:1.19-3.19), headstrong behaviors (RR = 1.91, CI:1.26-2.89), and inattention (RR = 1.56, CI:1.02-2.40).ConclusionsAdolescent survivors of Wilms tumor were similar to siblings with respect to mental health concerns overall but were more likely to require special education. Monitoring of psychosocial and academic problems through adolescence is warranted, especially among those treated with radiation to the abdomen plus chest or with cardiac conditions.
| S-EPMC7965255 | biostudies-literature
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.
| S-EPMC6788933 | 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:BackgroundGallbladder disease and need for cholecystectomy are common and significant contributors to patient morbidity and healthcare costs. Childhood cancer survivors are at elevated risk for developing cholelithiasis. However, their incidence of and risk factors for late (>5 years from diagnosis) cholecystectomy have not been studied.MethodsA total of 25,549 survivors (median age at diagnosis 6.9 years, range 0-21.0; current age 30.7 years, range 5.6-65.9) diagnosed between 1970 and 1999 and 5037 siblings were queried for self-reported cholecystectomy occurring five or more years from primary cancer diagnosis. Piecewise exponential models evaluated associations between cancer treatment exposures and late cholecystectomy.ResultsOver a median follow-up period of 21.9 and 26.0 years, respectively, 789 survivors and 168 siblings underwent late cholecystectomy (cumulative incidence 7.2%, 95% confidence interval [CI] = 6.5-7.8% and 6.6%, 95% CI = 5.4-7.6%, respectively; rate ratio [RR] = 1.3, 95% CI = 1.1-1.5). Compared with siblings, survivors of acute lymphoblastic leukaemia (RR = 1.4, 95% CI = 1.2-1.8), soft tissue sarcoma (RR = 1.4, 95% CI = 1.0-1.8) and bone cancer (RR = 1.3, 95% CI = 1.0-1.8) were at the greatest risk. In addition to attained age, female sex and increasing body mass index, exposure to high-dose (≥750 mg/m2) platinum chemotherapy (RR = 2.6, 95% CI = 1.5-4.5), vinca alkaloid chemotherapy (RR = 1.4, 95% CI = 1.1-1.8) or total body irradiation (TBI; RR = 2.2, 95% CI = 1.2-4.2) were each associated with late cholecystectomy.ConclusionsIndependent of traditional risk factors for gallbladder disease, exposure to high-dose platinum chemotherapy, vinca alkaloid chemotherapy or TBI increased risk for late cholecystectomy. These findings should inform current long-term follow-up guidelines and education regarding risk for late cholecystectomy.
| S-EPMC7365349 | biostudies-literature
Project description:PurposeNeurofibromatosis type 1 (NF1) is associated with tumor predisposition and nonmalignant health conditions. Whether survivors of childhood cancer with NF1 are at increased risk for poor long-term health outcomes is unknown.MethodsOne hundred forty-seven 5+ year survivors of childhood glioma with NF1 from the Childhood Cancer Survivor Study were compared with 2629 non-NF1 glioma survivors and 5051 siblings for late mortality, chronic health conditions, and psychosocial, neurocognitive, and socioeconomic outcomes.ResultsSurvivors with NF1 (age at diagnosis: 6.8 ± 4.8 years) had greater cumulative incidence of late mortality 30 years after diagnosis (46.3% [95% confidence interval: 23.9-62.2%]) compared with non-NF1 survivors (18.0% [16.1-20.0%]) and siblings (0.9% [0.6-1.2%]), largely due to subsequent neoplasms. Compared with survivors without NF1, those with NF1 had more severe/life-threatening chronic conditions at cohort entry (46.3% [38.1-54.4%] vs. 30.8% [29.1-32.6%]), but similar rates of new conditions during follow-up (rate ratio: 1.26 [0.90-1.77]). Survivors with NF1 were more likely to report psychosocial impairments, neurocognitive deficits, and socioeconomic difficulties compared with survivors without NF1.ConclusionsLate mortality among glioma survivors with NF1 is twice that of other survivors, due largely to subsequent malignancies. Screening, prevention, and early intervention for chronic health conditions and psychosocial and neurocognitive deficits may reduce long-term morbidity in this vulnerable population.
| S-EPMC7606750 | biostudies-literature
Project description:Recent advances in childhood cancer treatment have increased survival rates to 80%. Two out of three survivors experience late effects (LEs). From a group of 241 survivors previously described, 193 were followed at the long-term follow-up clinic (LTFC) of Severance Hospital in Korea; the presence of LEs was confirmed by oncologists. We reported the change in LEs during 3 yr of follow-up. The median follow-up from diagnosis was 10.4 yr (5.1-26.2 yr). Among 193 survivors, the percentage of patients with at least one LE increased from 63.2% at the initial visit to 75.1% at the most recent visit (P = 0.011). The proportion of patients having multiple LEs and grade 2 or higher LEs increased from the initial visit (P = 0.001 respectively). Forty-eight non-responders to the LTFC were older and had less frequent and severe LEs than responders at initial visit (all P < 0.05). In multivariate analysis, younger age at diagnosis, older age at initial visit, a diagnosis of a brain tumor or lymphoma, and use of radiotherapy were significant risk factors for LEs (all P < 0.05). Adverse changes in LEs were seen among the survivors, regardless of most clinical risk factors. They need to receive comprehensive, long-term follow up.
| S-EPMC3653090 | biostudies-other
Project description:BackgroundLimited data are available on the risk factors of salivary gland dysfunction in long-term childhood cancer survivors (CCS). The objective of this cross-sectional study, part of the multidisciplinary multicenter Dutch CCS Study Late Effects 2 (DCCSS LATER 2), was to assess the prevalence of and risk factors for hyposalivation and xerostomia in CCS.MethodsFrom February 2016 until March 2020, 292 CCS were included. Data with regard to gender, age at study, diagnosis, age at diagnosis, and treatment characteristics were collected, as well as the unstimulated (UWS) and stimulated whole salivary flow rate (SWS). Xerostomia was assessed with the Xerostomia Inventory (XI) questionnaire. Multivariable Poisson regression analyses were used to evaluate the association between potential risk factors and the occurrence of hyposalivation.ResultsThe minimum time between diagnosis and study enrollment was 15 years. The prevalence of hyposalivation was 32% and the prevalence of xerostomia was 9.4%. Hyposalivation and xerostomia were not significantly correlated. Risk factors for hyposalivation were female gender and a higher dose of radiotherapy (>12 Gy) to the salivary gland region.ConclusionConsidering the importance of saliva for oral health, screening for hyposalivation in CCS is suggested in order to provide optimal oral supportive care aimed to improve oral health.
| S-EPMC9320024 | biostudies-literature
Project description:BackgroundThe occurrence of subsequent neoplasms has direct impact on the quantity and quality of life in cancer survivors. We have expanded our analysis of these events in the Childhood Cancer Survivor Study (CCSS) to better understand the occurrence of these events as the survivor population ages.MethodsThe incidence of and risk for subsequent neoplasms occurring 5 years or more after the childhood cancer diagnosis were determined among 14,359 5-year survivors in the CCSS who were treated from 1970 through 1986 and who were at a median age of 30 years (range = 5-56 years) for this analysis. At 30 years after childhood cancer diagnosis, we calculated cumulative incidence at 30 years of subsequent neoplasms and calculated standardized incidence ratios (SIRs), excess absolute risks (EARs) for invasive second malignant neoplasms, and relative risks for subsequent neoplasms by use of multivariable Poisson regression.ResultsAmong 14,359 5-year survivors, 1402 subsequently developed 2703 neoplasms. Cumulative incidence at 30 years after the childhood cancer diagnosis was 20.5% (95% confidence interval [CI] = 19.1% to 21.8%) for all subsequent neoplasms, 7.9% (95% CI = 7.2% to 8.5%) for second malignant neoplasms (excluding nonmelanoma skin cancer), 9.1% (95% CI = 8.1% to 10.1%) for nonmelanoma skin cancer, and 3.1% (95% CI = 2.5% to 3.8%) for meningioma. Excess risk was evident for all primary diagnoses (EAR = 2.6 per 1000 person-years, 95% CI = 2.4 to 2.9 per 1000 person-years; SIR = 6.0, 95% CI = 5.5 to 6.4), with the highest being for Hodgkin lymphoma (SIR = 8.7, 95% CI = 7.7 to 9.8) and Ewing sarcoma (SIR = 8.5, 95% CI = 6.2 to 11.7). In the Poisson multivariable analysis, female sex, older age at diagnosis, earlier treatment era, diagnosis of Hodgkin lymphoma, and treatment with radiation therapy were associated with increased risk of subsequent neoplasm.ConclusionsAs childhood cancer survivors progress through adulthood, risk of subsequent neoplasms increases. Patients surviving Hodgkin lymphoma are at greatest risk. There is no evidence of risk reduction with increasing duration of follow-up.
| S-EPMC2907408 | biostudies-literature