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Approach for Classification and Severity Grading of Long-term and Late-Onset Health Events among Childhood Cancer Survivors in the St. Jude Lifetime Cohort.

ABSTRACT: Characterization of toxicity associated with cancer and its treatment is essential to quantify risk, inform optimization of therapeutic approaches for newly diagnosed patients, and guide health surveillance recommendations for long-term survivors. The NCI Common Terminology Criteria for Adverse Events (CTCAE) provides a common rubric for grading severity of adverse outcomes in cancer patients that is widely used in clinical trials. The CTCAE has also been used to assess late cancer treatment-related morbidity but is not fully representative of the spectrum of events experienced by pediatric and aging adult survivors of childhood cancer. Also, CTCAE characterization does not routinely integrate detailed patient-reported and medical outcomes data available from clinically assessed cohorts. To address these deficiencies, we standardized the severity grading of long-term and late-onset health events applicable to childhood cancer survivors across their lifespan by modifying the existing CTCAE v4.03 criteria and aligning grading rubrics from other sources for chronic conditions not included or optimally addressed in the CTCAE v4.03. This article describes the methods of late toxicity assessment used in the St. Jude Lifetime Cohort Study, a clinically assessed cohort in which data from multiple diagnostic modalities and patient-reported outcomes are ascertained. Cancer Epidemiol Biomarkers Prev; 26(5); 666-74. ©2016 AACR.

SUBMITTER: Hudson MM

PROVIDER: S-EPMC5413397 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Approach for Classification and Severity Grading of Long-term and Late-Onset Health Events among Childhood Cancer Survivors in the St. Jude Lifetime Cohort.

Hudson Melissa M MM Ehrhardt Matthew J MJ Bhakta Nickhill N Baassiri Malek M Eissa Hesham H Chemaitilly Wassim W Green Daniel M DM Mulrooney Daniel A DA Armstrong Gregory T GT Brinkman Tara M TM Klosky James L JL Krull Kevin R KR Sabin Noah D ND Wilson Carmen L CL Huang I-Chan IC Bass Johnnie K JK Hale Karen K Kaste Sue S Khan Raja B RB Srivastava Deo Kumar DK Yasui Yutaka Y Joshi Vijaya M VM Srinivasan Saumini S Stokes Dennis D Hoehn Mary Ellen ME Wilson Matthew M Ness Kirsten K KK Robison Leslie L LL

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20161229 5

Characterization of toxicity associated with cancer and its treatment is essential to quantify risk, inform optimization of therapeutic approaches for newly diagnosed patients, and guide health surveillance recommendations for long-term survivors. The NCI Common Terminology Criteria for Adverse Events (CTCAE) provides a common rubric for grading severity of adverse outcomes in cancer patients that is widely used in clinical trials. The CTCAE has also been used to assess late cancer treatment-rel ...[more]

PMID: 28035022

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Project description:BackgroundSurvivors of childhood cancer have an increased risk of therapy-related cardiovascular disease. It is not known whether family history of cardiovascular disease further increases risk of adverse cardiovascular outcomes among survivors.MethodsFamily history of cardiovascular disease was collected from 1,260 survivors [median age at diagnosis, 8 years (range, 0-23); age at last follow-up, 35 years (range, 18-66)] of childhood cancer in the St. Jude Lifetime Cohort Study. Multivariable risk models evaluated associations with cardiovascular disease (Common Terminology Criteria for Adverse Events grade 2-4 events) and cardiovascular risk factors.ResultsAmong survivors exposed to chest-directed radiation and/or anthracycline chemotherapy (n = 824), 7% reported a first-degree family history of heart failure, 19% myocardial infarction, 11% stroke, 26% atherosclerotic disease (myocardial infarction and/or stroke), 62% hypertension, and 31% diabetes mellitus. Eighteen percent of exposed survivors developed heart failure, 9% myocardial infarction, 3% stroke, 11% atherosclerotic disease, 30% hypertension, and 9% diabetes mellitus. Having a first-degree family history of atherosclerotic disease was independently associated with development of treatment-related heart failure [RR, 1.38; 95% confidence interval (CI), 1.01-1.88; P = 0.04] among exposed survivors. Risk for hypertension was increased among exposed survivors with a first-degree family history of hypertension (RR, 1.55; 95% CI, 1.26-1.92; P < 0.0001) or of any cardiovascular disease [myocardial infarction, stroke, or heart failure (RR, 1.30; 95% CI, 1.06-1.59; P = 0.01)].ConclusionsFamily history of cardiovascular disease and cardiovascular risk factors independently increased risk of heart failure and hypertension among survivors of childhood cancer exposed to cardiotoxic therapies.ImpactThese data show the importance of cardiovascular family history as a risk factor for cardiovascular disease in survivors of childhood cancer.

Project description:IntroductionThere is a growing population of childhood cancer survivors at risk for adverse outcomes, including sexual dysfunction.AimTo estimate the prevalence of and risk factors for sexual dysfunction among adult female survivors of childhood cancer and evaluate associations between dysfunction and psychological symptoms/quality of life (QOL).MethodsFemale survivors (N = 936, mean 7.8 ± 5.6 years at diagnosis; 31 ± 7.8 years at evaluation) and noncancer controls (N = 122) participating in the St. Jude Lifetime Cohort Study completed clinical evaluations, Sexual Functioning Questionnaires (SFQ), and Medical Outcomes Survey Short Forms 36 (SF-36). Linear models compared SFQ scores between sexually active survivors (N = 712) and controls; survivors with scores <10th percentile of controls were classified with sexual dysfunction. Logistic regression evaluated associations between survivor characteristics and sexual dysfunction, and between sexual dysfunction and QOL.OutcomesSexual dysfunction was defined by scores <10th percentile of noncancer controls on the SFQ overall, as well as the domains of arousal, interest, orgasm, and physical problems, while QOL was measured by scores on the SF-36 with both physical and mental summary scales.ResultsSexual dysfunction was prevalent among 19.9% (95% CI 17.1, 23.1) of survivors. Those diagnosed with germ cell tumors (OR = 8.82, 95% CI 3.17, 24.50), renal tumors (OR = 4.49, 95% CI 1.89, 10.67), or leukemia (OR = 3.09, 95% CI 1.50, 6.38) were at greater risk compared to controls. Age at follow-up (45-54 vs 18-24 years; OR = 5.72, 95% CI 1.87, 17.49), pelvic surgery (OR = 2.03, 95% CI 1.18, 3.50), and depression (OR = 1.96, 95% CI 1.10, 3.51) were associated with sexual dysfunction. Hypogonadism receiving hormone replacement (vs nonmenopausal/nonhypogonadal; OR = 3.31, 95% CI 1.53, 7.15) represented an additional risk factor in the physical problems (eg, vaginal pain and dryness) subscale. Survivors with sexual dysfunction, compared to those without sexual dysfunction, were more likely to score <40 on the physical (21.1% vs 12.7%, P = .01) and mental health (36.5% vs 18.2%, P < .01) summary scales of the SF-36. Only 2.9% of survivors with sexual dysfunction reported receiving intervention.Clinical implicationsHealth care providers should be aware of the increased risk of sexual dysfunction in this growing population, inquire about symptomology, and refer for appropriate intervention.Strengths & limitationsStrengths of this study include the use of a validated tool for evaluating sexual function in a large population of clinically assessed female childhood cancer survivors. Limitations include potential for selection bias, and lack of clinically confirmed dysfunction.ConclusionSexual dysfunction is prevalent among female childhood cancer survivors and few survivors receive intervention; further research is needed to determine if those with sexual dysfunction would benefit from targeted interventions. Bjornard KL, Howell CR, Klosky JL, et al. Psychosexual Functioning of Female Childhood Cancer Survivors: A Report From the St. Jude Lifetime Cohort Study. J Sex Med 2020;17:1981-1994.

Project description:BackgroundSuicide is a serious public health concern. An increased risk of suicide ideation previously has been reported among survivors of childhood cancer.MethodsSuicide mortality was assessed for all potentially eligible survivors (those aged ≥18 years who were ≥5 years after their cancer diagnosis; 7312 survivors). Risk factors for acute suicidal ideation were assessed among clinically evaluated survivors (3096 survivors) and the prevalence of acute ideation was compared with that of community controls (429 individuals). The prevalence of 12-month suicidality was assessed among survivors who could be compared with population data (1255 survivors). Standardized mortality ratios compared rates of suicide mortality among survivors with those of the general population. Risk ratios (RRs) and 95% confidence intervals (95% CIs) derived from generalized linear models identified risk factors associated with acute suicidal ideation. Standardized incidence ratios (SIRs) compared the prevalence of 12-month suicidality among survivors with that of a matched sample from the general population.ResultsSurvivors reported a similar 12-month prevalence of ideation compared with the general population (SIR, 0.68; 95% CI, 0.35-1.01) and a lower prevalence of suicidal behaviors (planning: SIR, 0.17 [95% CI, 0.07-0.27]; attempts: SIR, 0.07 [95% CI, 0.00-0.15]) and mortality (standardized mortality ratio, 0.60; 95% CI, 0.34-0.86). Among survivors, depression (RR, 12.30; 95% CI, 7.89-19.11), anxiety (RR, 2.19; 95% CI, 1.40-3.40), and financial stress (RR, 1.47; 95% CI, 1.00-2.15) were found to be associated with a higher prevalence of acute suicidal ideation.ConclusionsSurvivors of childhood cancer were found to be at a lower risk of suicidal behaviors and mortality, yet endorsed a prevalence of ideation similar to that of the general population. These results are in contrast to previous findings of suicidal ideation among survivors and support the need for further research to inform screening strategies and interventions.Lay summaryThe purpose of the current study was to compare the risk of suicidal ideation, behaviors, and mortality in adult survivors of childhood cancer with those of the general population. Risk factors associated with suicidal ideation among survivors of childhood cancer also were examined. Survivors of childhood cancer reported a similar risk of ideation compared with the general population, but a lower risk of suicidal behaviors and mortality. Psychological health and financial stressors were found to be risk factors associated with suicidal ideation. Although adult survivors of childhood cancer did not report a greater risk of suicidality compared with the general population, psychosocial care in survivorship remains essential.

Project description:PURPOSE:To examine prevalence and predictors of neurocognitive outcomes, social attainment, emotional distress, and health-related quality of life (HRQOL) in long-term survivors of pediatric Wilms tumor (WT). METHODS:One hundred fifty-eight WT survivors (59% female; mean [SD] age 33 [9.1] years; time since diagnosis 29 [9.1] years) and 354 community controls (55.6% female; 35 [10.2] years) completed comprehensive neuropsychological testing and physical examination, including echocardiography/electrocardiography, pulmonary function tests, and endocrine evaluation. Self-report of emotional distress, HRQOL, and social attainment were collected. Impairment was defined in relation to both controls and normative data. Generalized linear models were developed to examine impact of treatment and chronic health conditions on outcomes. RESULTS:WT survivors performed poorer than norms and controls in 6 of 16 cognitive variables and 1 of 8 HRQOL variables, with scores ranging from - 0.64 (mathematics) to - 0.21 (verbal fluency) standard deviations below expectations. Compared to controls, WT survivors were less likely to graduate college (odds ratio 2.23, 95% confidence interval 1.46-3.41) and had more moderate to severe neurologic conditions (18.4% vs 8.2%, p < 0.001), which were associated with poor memory (β = - 0.90, p < 0.001), attention (β = - 1.02, p < 0.001), and HRQOL general health (β = - 0.80, p = 0.0015). Treatment variables and cardiopulmonary morbidity (higher in survivors) were not associated with outcomes. CONCLUSIONS:Survivors of WT demonstrate impairment in neurocognitive function and have lower social attainment during adulthood, with poorer neurocognitive function associated with neurologic morbidity. IMPLICATIONS FOR CANCER SURVIVORS:Survivors of WT should be offered neurocognitive evaluations and rehabilitation. Neurologic conditions should be routinely assessed, and appropriate support offered to reduce risk for functional limitations.

Dataset Information

Approach for Classification and Severity Grading of Long-term and Late-Onset Health Events among Childhood Cancer Survivors in the St. Jude Lifetime Cohort.

Publications

Approach for Classification and Severity Grading of Long-term and Late-Onset Health Events among Childhood Cancer Survivors in the St. Jude Lifetime Cohort.

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