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Background: Survivors of childhood central nervous system (CNS) tumors can develop motor and sensory impairment from their cancer and treatment history. We estimated the prevalence of motor and sensory impairment in survivors compared with controls through clinical assessment and identified associated treatment exposures and functional, quality of life (QOL), and social outcomes., Methods: Survivors of childhood CNS tumors from the St. Jude Lifetime Cohort (n = 378, median [range] age 24.0 [18.0-53.0] years, 43.4% female) ≥5 years from diagnosis and controls (n = 445, median [range] age 34.0 [18.0-70.0] years, 55.7% female) completed in-person evaluation for motor and sensory impairment using the modified Total Neuropathy Score. Impairment was graded by modified Common Terminology Criteria for Adverse Events. Multivariable models estimated associations between grade ≥2 motor/sensory impairment, individual/treatment characteristics, and secondary outcomes (function by Physical Performance Test, fitness by physiologic cost index, QOL by Medical Outcomes Survey Short Form-36 physical/mental summary scores, social attainment)., Results: Grade ≥2 motor or sensory impairment was more prevalent in survivors (24.1%, 95% Confidence Interval [CI] 19.8%-29.4%) than controls (2.9%, CI 1.4-4.5%). Among survivors, in multivariable models, motor impairment was associated with vinca exposure <15 mg/m 2 versus none (OR 4.38, CI 1.06-18.08) and etoposide exposure >2036 mg/m 2 versus none (OR 12.61, CI 2.19-72.72). Sensory impairment was associated with older age at diagnosis (OR 1.09, CI 1.01-1.16) and craniospinal irradiation versus none (OR 4.39, CI 1.68-11.50). There were lower odds of motor/sensory impairment in survivors treated in the year 2000 or later versus before 1990 (Motor: OR 0.29, CI 0.10-0.84, Sensory: OR 0.35, CI 0.13-0.96). Motor impairment was associated with impaired physical QOL (OR 2.64, CI 1.22-5.72)., Conclusions: In survivors of childhood CNS tumors, motor and sensory impairment is prevalent by clinical assessment, especially after exposure to etoposide, vinca, or craniospinal radiation. Treating motor impairment may improve survivors' QOL., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Childhood cancer survivors are at high risk for morbidity and mortality and poor patient-reported outcomes, typically health-related quality of life (HRQOL). However, associations between DNA methylation-based aging biomarkers and HRQOL have not been evaluated., Methods: DNA methylation was generated with Infinium EPIC BeadChip on blood-derived DNA (median for age at blood draw = 34.5 years, range = 18.5-66.6 years), and HRQOL was assessed with age at survey (mean = 32.3 years, range = 18.4-64.5 years) from 2206 survivors in the St Jude Lifetime Cohort. DNA methylation-based aging biomarkers, including epigenetic age using multiple clocks (eg, GrimAge) and others (eg, DNAmB2M: beta-2-microglobulin; DNAmADM: adrenomedullin), were derived from the DNAm Age Calculator (https://dnamage.genetics.ucla.edu). HRQOL was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey to capture 8 domains and physical and mental component summaries. General linear models evaluated associations between HRQOL and epigenetic age acceleration (EAA; eg, EAA&#95;GrimAge) or other age-adjusted DNA methylation-based biomarkers (eg, ageadj&#95;DNAmB2M) after adjusting for age at blood draw, sex, cancer treatments, and DNA methylation-based surrogate for smoking pack-years. All P values were 2-sided., Results: Worse HRQOL was associated with greater EAA&#95;GrimAge (physical component summaries: β = -0.18 years, 95% confidence interval [CI] = -0.251 to -0.11 years; P = 1.85 × 10-5; and 4 individual HRQOL domains), followed by ageadj&#95;DNAmB2M (physical component summaries: β = -0.08 years, 95% CI = -0.124 to -0.037 years; P = .003; and 3 individual HRQOL domains) and ageadj&#95;DNAmADM (physical component summaries: β = -0.082 years, 95% CI = -0.125 to -0.039 years; P = .002; and 2 HRQOL domains). EAA&#95;Hannum (Hannum clock) was not associated with any HRQOL., Conclusions: Overall and domain-specific measures of HRQOL are associated with DNA methylation measures of biological aging. Future longitudinal studies should test biological aging as a potential mechanism underlying the association between poor HRQOL and increased risk of clinically assessed adverse health outcomes., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Importance: Symptom burden and its characteristics among survivors of pediatric cancers aged 8 to 18 years remain understudied., Objective: To examine the prevalence of symptom burden among young childhood cancer survivors and identify associations with sociodemographic, clinical, and psychological resilience skills, and health-related quality of life (HRQOL)., Design, Setting, and Participants: A cross-sectional analysis using data collected from November 1, 2017, to January 31, 2019, in a survivorship clinic at a US-based comprehensive cancer center was conducted. Participants included 302 dyads of children aged 8 to 18 years who survived at least 5 years beyond diagnosis and their primary caregivers. Data analysis was performed from March 13, 2023, to February 29, 2024., Exposures: Diagnosis, caregiver-reported family conflict, self-reported caregiver anxiety, neighborhood-level social vulnerability, and survivor-reported meaning and purpose., Main Outcomes and Measures: Novel symptom-level burden, integrating the attributes of severity and daily activity interference using the pediatric version of the Patient-Reported Outcomes Version of the Common Terminology Criteria for Adverse Events, global cumulative symptom burden, and HRQOL using the EuroQol-5D. Multinomial logistic regression identified characteristics associated with symptom burden; linear regression assessed symptom burden and HRQOL associations., Results: Among 302 survivors (mean [SD] age, 14.2 [2.9] years, mean [SD] time since diagnosis, 10.9 [2.9] years; 153 [50.7%] male), 186 (62.0%) had low, 77 (25.7%) moderate, and 37 (12.3%) high global cumulative symptom burden. Greater caregiver anxiety was associated with moderate (risk ratio [RR], 1.56; 95% CI, 1.09-2.24) global symptom burden. Greater neighborhood deprivation was associated with moderate global symptom burden (RR, 4.86; 95% CI, 1.29-18.26). Survivors with greater meaning/purpose were less likely to have moderate (RR, 0.42; 95% CI, 0.29-0.61) and high (RR, 0.27; 95% CI, 0.16-0.46) global symptom burden. The burden of individual symptoms displayed similar patterns. Low (Cohen d, -0.60; 95% CI, -0.87 to -0.32) and moderate/high (d, -0.98; 95% CI, -1.53 to -0.43) general pain, moderate/high numbness (d, -0.99; 95% CI, -1.69 to -0.29), and moderate/high worry (d, -0.55; 95% CI, -0.99 to -0.11) were associated with lower HRQOL., Conclusions and Relevance: In this cross-sectional study of young childhood cancer survivors, symptom burden was prevalent. Caregiver anxiety and disparity-related neighborhood factors were associated with greater symptom burden, whereas meaning and purpose was a protective factor. Greater specific symptom burden contributed to poorer HRQOL. The findings suggest that interventions targeting resilience and neighborhood adversity may alleviate symptom burden and improve HRQOL.

Purpose: Health utility (HU) is a useful metric for evaluating cost and utility of cancer therapies or prioritizing healthcare resources. We conducted a meta-analysis to compare HUs in association with clinical parameters and identify missing cancer-related themes from the extant HU measures for pediatric cancer patients and survivors., Methods: Studies published in the PubMed, Embase, Web of Science, and Cochrane Library were identified. Meta-analyses were performed to estimate weighted means of HUs assessed by self- and proxy-responses. Mixed-effects meta-regressions were applied to compare HUs between cancer patients/survivors and general populations. Missing themes in the extant measures were identified based on established patient-reported outcomes frameworks., Results: Of 123 selected studies included pediatric cancer populations, 44% used the Health Utilities Index version 2 (HUI2), and 48% used version 3 (HUI3). Compared to general populations, cancer patients undergoing therapies for acute lymphoblastic leukemia (ALL) had 0.129 (95% CI - 0.183 to - 0.075) and brain tumor had 0.257 (95% CI - 0.354 to - 0.160) lower HUs per proxy-reported HUI3, whereas survivors of ALL had 0.028 (95% CI - 0.062 to 0.007) and brain tumor had 0.188 (95% CI - 0.237 to - 0.140) lower HUs per proxy-reported HUI3. Compared to general populations, cancer patients treated with multimodality therapy and survivors off therapy 2-5 years had significantly poorer HUs (p's < 0.05). Missing cancer-specific contents from the HU measures were identified., Conclusion: Pediatric cancer patients and survivors had poorer HUs than general populations. It is important to select appropriate HUs for economic evaluations, and offer interventions to minimize HU deficits for particular cancer populations., (© 2021. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Importance: Exercise intolerance is associated with increased risk for morbidity and mortality in childhood cancer survivors. However, an association between exercise intolerance and psychosocial outcomes has not been fully explored., Objective: To examine the associations between exercise intolerance and emotional distress, attainment of social roles, and health-related quality of life in childhood cancer survivors., Design, Setting, and Participants: A cross-sectional study including 1041 adult survivors of childhood cancer and 286 community controls in the St Jude Lifetime Cohort was conducted at St Jude Children's Research Hospital. The study was performed from April 1, 2012, to March 15, 2020., Exposures: Exercise intolerance was defined as relative peak oxygen uptake less than 85% of age- and sex-estimated levels from maximal cardiopulmonary exercise testing., Main Outcomes and Measures: Emotional distress was measured with the 18-item Brief Symptom Inventory-18, which includes overall Global Severity Index and depression, anxiety, and somatization subscales. Participants with T scores greater than or equal to 63 were classified as having elevated levels of distress. Social attainment was evaluated using patient-reported educational, employment, and marital status. Health-related quality of life was examined with the Medical Outcomes Survey Short Form-36. Participants with T scores less than or equal to 40 were classified as reporting poor health-related quality of life., Results: Of the 1041 participants, 528 were women (50.7%). The prevalence of exercise intolerance among survivors (mean [SD] age, 35.5 [9.2] years) was higher than that among controls (age, 34.5 [10.0] years) (survivors: 634 [60.9%] vs controls: 75 [26.2%], P < .001). After adjusting for age at diagnosis and cardiopulmonary exercise testing, sex, race/ethnicity, smoking, physical activity, and exercise intolerance were associated with an increased risk for anxiety (prevalence rate ratio [PRR], 1.95; 95% CI, 1.20-3.16), somatization (PRR, 1.86; 95% CI, 1.23-2.80), and unemployment (PRR, 1.76; 95% CI, 1.23-2.52); an inverse association was noted with having a college degree (PRR, 0.67; 95% CI, 0.50-0.88). Exercise intolerance was associated with an increased the risk for scoring less than or equal to 40 on the physical component summary of the Medical Outcomes Survey Short Form-36 (PRR, 3.69; 95% CI, 2.34-5.84). These associations persisted when either cancer treatment exposures or chronic health conditions were added to the model., Conclusions and Relevance: The findings of this study suggest that exercise intolerance is independently associated with emotional distress, attainment of social roles, and health-related quality of life of long-term survivors of childhood cancer. The results also suggest that improving physiologic capacity may benefit general health and wellness, as well as emotional health, ability to participate in social roles, and health-related quality of life.

Patient-reported outcomes among survivors of pediatric hematopoietic stem cell transplant (HSCT) are understudied. We compared symptom prevalence, health-related quality of life (HRQOL), and risk factors in adult survivors of childhood hematologic malignancies treated with HSCT to those treated with conventional therapy and noncancer controls. Survivors of childhood hematologic malignancies (HSCT N = 112 [70% allogeneic, 30% autologous]; conventionally treated N = 1106) and noncancer controls (N = 242) from the St. Jude Lifetime Cohort Study completed surveys assessing 10 symptom domains and SF-36 HRQOL summary scores. Chronic health conditions (CHCs) were validated by clinical assessment. Multivariable logistic regression reveals that compared with noncancer controls, HSCT survivors endorsed a significantly higher symptom prevalence in sensation (OR = 4.7, 95% confidence interval [CI], 2.6-8.4), motor/movement (OR = 4.3, 95% CI, 1.6-11.0), pulmonary (OR = 4.6, 95% CI, 1.8-11.8), and memory domains (OR = 4.8, 95% CI, 2.5-9.2), and poorer physical HRQOL (OR = 6.9, 95% CI, 2.8-17.0). HSCT and conventionally treated survivors had a similar prevalence of all symptom domains and HRQOL (all P > .05); however, HSCT survivors had a significantly higher cumulative prevalence for specific symptoms: double vision (P = .04), very dry eyes (P < .0001), and trouble seeing when wearing glasses (P < .0001). Occurrence of organ-specific CHCs, instead of transplant receipt, was significantly associated with a higher prevalence of all symptom domains (all P < .05) in adult survivors of childhood cancer, except for pain and anxiety domains. This study found that patient-reported outcomes were equally impaired between HSCT and conventionally treated survivors, but poorer in both groups compared with noncancer controls. Poor patient-reported outcomes in all survivors of childhood hematologic malignancies correlated with the presence of CHCs, whether treated with conventional therapy or HSCT., (© 2020 by The American Society of Hematology.)

Background: The objective of this study was to characterize chronic disease, health-related quality of life (HRQOL), emotional distress, and social attainment among long-term survivors of neuroblastoma., Methods: Chronic health conditions among 136 ≥10-year neuroblastoma survivors (median age, 31.9 years; range, 20.2-54.6 years) and 272 community controls (median age, 34.7 years; range, 18.3-59.6 years) were graded with a modified version of the Common Terminology Criteria for Adverse Events (version 4.03). HRQOL and emotional distress were assessed with the Medical Outcomes Study 36-Item Short Form Health Survey and the Brief Symptom Inventory-18. Log-binomial regression and logistic regression were used to compare the prevalence of chronic conditions and the frequency of reduced HRQOL, distress, and social attainment between survivors and controls. The cumulative burden approach was used to estimate multimorbidity., Results: By the age of 35 years, survivors had experienced, on average, 8.5 grade 1 to 5 conditions (95% confidence interval [CI], 7.6-9.3), which was higher than the average for controls (3.3; 95% CI, 2.9-3.7). Compared with controls, survivors had a higher prevalence of any pulmonary (P = .003), auditory (P < .001), gastrointestinal (P < .001), neurological (P = .003), or renal condition (P < .001); were more likely to report poor physical HRQOL (P = .01) and symptoms of anxiety (P = .01) and somatization (P = .01); and were less likely to live independently (P = .01) or marry (P = .01). In analyses limited to survivors, those with 1 or more grade 3 to 5 conditions were more likely to report reduced general health (odds ratio [OR], 6.6; 95% CI, 1.6-26.9), greater bodily pain (OR, 4.2; 95% CI, 1.0-17.0), and unemployment (OR, 3.2; 95% CI, 1.2-8.5)., Conclusions: Because of the high burden of chronic diseases and the associations of these morbidities with reduced HRQOL and social attainment, screening and interventions that provide opportunities to optimize health are important among neuroblastoma survivors., (© 2020 American Cancer Society.)

Background: Glucocorticoids used to treat childhood leukemia and lymphoma can result in osteonecrosis, leading to physical dysfunction and pain. Improving survival rates warrants research into long-term outcomes among this population., Objective: The objective of this study was to compare the physical function and quality of life (QOL) of survivors of childhood cancer who had an osteonecrosis history with that of survivors who had no osteonecrosis history and with that of people who were healthy (controls)., Design: This was a cross-sectional study., Methods: This study included St Jude Lifetime Cohort Study participants who were ≥ 10 years from the diagnosis of childhood leukemia or lymphoma and ≥ 18 years old; 135 had osteonecrosis (52.5% men; mean age = 27.7 [SD = 6.08] years) and 1560 had no osteonecrosis history (52.4% men; mean age = 33.3 [SD = 8.54] years). This study also included 272 people who were from the community and who were healthy (community controls) (47.7% men; mean age = 35.1 [SD = 10.46] years). The participants completed functional assessments and questionnaires about QOL., Results: Survivors with osteonecrosis scored lower than other survivors and controls for dorsiflexion strength (mean score = 16.50 [SD = 7.91] vs 24.17 [SD = 8.61] N·m/kg) and scored lower than controls for flexibility with the sit-and-reach test (20.61 [SD = 9.70] vs 23.96 [SD = 10.73] cm), function on the Physical Performance Test (mean score = 22.73 [SD = 2.05] vs 23.58 [SD = 0.88]), and mobility on the Timed "Up & Go" Test (5.66 [SD = 2.25] vs 5.12 [SD = 1.28] seconds). Survivors with hip osteonecrosis requiring surgery scored lower than survivors without osteonecrosis for dorsiflexion strength (13.75 [SD = 8.82] vs 18.48 [SD = 9.04] N·m/kg), flexibility (15.79 [SD = 8.93] vs 20.37 [SD = 10.14] cm), and endurance on the 6-minute walk test (523.50 [SD = 103.00] vs 572.10 [SD = 102.40] m)., Limitations: Because some eligible survivors declined to participate, possible selection bias was a limitation of this study., Conclusions: Survivors of childhood leukemia and lymphoma with and without osteonecrosis demonstrated impaired physical performance and reported reduced QOL compared with controls, with those requiring surgery for osteonecrosis most at risk for impairments. It may be beneficial to provide strengthening, flexibility, and endurance interventions for patients who have pediatric cancer and osteonecrosis for long-term function., (© 2020 American Physical Therapy Association.)

Purpose: This study compared the measurement properties for multiple modes of survey administration, including postal mail, telephone interview, and Web-based completion of patient-reported outcomes (PROs) among survivors of childhood cancer., Methods: The population included 6,974 adult survivors of childhood cancer in the Childhood Cancer Survivor Study who completed the Brief Symptom Inventory-18 (BSI-18), which measured anxiety, depression, and somatization symptoms. Scale reliability, construct validity, and known-groups validity related to health status were tested for each mode of completion. The multiple indicators and multiple causes technique was used to identify differential item functioning (DIF) for the BSI-18 items that responded through a specific survey mode. The impact of the administration mode was tested by comparing differences in BSI-18 scores between the modes accounting for DIF effects., Results: Of the respondents, 58%, 27%, and 15% completed postal mail, Web-based, and telephone surveys, respectively. Survivors who were male; had lower education, lower household income, or poorer health status; or were treated with cranial radiotherapy were more likely to complete a telephone-based survey compared with either a postal mail or Web-based survey (all P < .05). Scale reliability and validity were equivalent across the 3 survey options. One, 2, and 5 items from the anxiety, depression, and somatization domains, respectively, were identified as having significant DIF among survivors who responded by telephone ( P < .05). However, estimated BSI-18 domain scores, especially depression and anxiety, between modes did not differ after accounting for DIF effects., Conclusion: Certain survivor characteristics were associated with choosing a specific mode for PRO survey completion. However, measurement properties among these modes were equivalent, and the impact of using a specific mode on scores was minimal.

Background: There are limited data describing fitness and associated health-related quality of life (HRQoL) in survivors of childhood Hodgkin lymphoma (HL)., Procedure: Fitness was evaluated among 336 adult survivors of childhood-onset HL treated at St. Jude Children's Research Hospital and 327 controls who never had childhood cancer. The controls were frequency matched on age, sex, and race. Associations were examined between chronic disease and fitness and between fitness and HRQoL using a multivariable linear and logistic regression., Results: Male survivors had lower endurance (6-min walk [6MW] distance 604.4 ± 7.9 m vs 637.0 ± 7.5 m, P < 0.01), and worse neuropathy (modified Total Neuropathy Score [mTNS] 2.7 ± 0.2 vs 1.4 ± 0.2, P < 0.01) compared to controls. Female survivors had lower endurance (6MW distance 564.5 ± 6.9 m vs 590.6 ± 7.0 m, P < 0.01), quadriceps strength (145.7 ± 4.0 vs 163.4 ± 4.0 N·m per kilogram, P < 0.01), and worse neuropathy (mTNS 3.2 ± 0.2 vs 1.4 ± 0.3, P < 0.01) compared to controls. Moderate, severe/disabling, or life-threatening (grades 2-4) neurological conditions were associated with impaired quadriceps strength (odds ratio [OR] 2.94, 99% confidence interval [CI] 1.24-6.96) and impaired endurance (OR 2.96, 99% CI 1.28-6.69). Cardiovascular (OR 2.36, 99% CI 1.00-5.61) and pulmonary (OR 2.78, 99% CI 1.30-5.94) conditions were associated with impaired endurance. Quadriceps strength (β -6.44 ± 2.01, P < 0.01), endurance (β -4.63 ± 1.54, P < 0.01), and neuropathy (β -4.98 ± 1.14, P < 0.01) were associated with a lower physical component summary on the HRQoL., Conclusion: Survivors of childhood HL, particularly those with neurological, cardiac, and pulmonary chronic conditions, are at risk for impaired fitness and HRQoL., (© 2018 Wiley Periodicals, Inc.)

Background: Financial hardship among survivors of pediatric cancer has been understudied. We investigated determinants and consequences of financial hardship among adult survivors of childhood cancer., Methods: Financial hardship, determinants, and consequences were examined in 2811 long-term survivors (mean age at evaluation = 31.8 years, years postdiagnosis = 23.6) through the baseline survey and clinical evaluation. Financial hardship was measured by material, psychological, and coping/behavioral domains. Outcomes included health and life insurance affordability, retirement planning, symptoms, and health-related quality of life (HRQOL). Odds ratios (ORs) estimated associations of determinants with financial hardship. Odds ratios and regression coefficients estimated associations of hardship with symptom prevalence and HRQOL, respectively. All statistical tests were two-sided., Results: Among participants, 22.4% (95% confidence interval [CI] = 20.8% to 24.0%), 51.1% (95% CI = 49.2% to 52.9%), and 33.0% (95% CI = 31.1% to 34.6%) reported material, psychological, and coping/behavioral hardship, respectively. Risk factors across hardship domains included annual household income of $39 999 or less vs $80 000 or more (material OR = 3.04, 95% CI = 2.08 to 4.46, psychological OR = 3.64, 95% CI = 2.76 to 4.80, and coping/behavioral OR = 4.95, 95% CI = 3.57 to 6.86) and below high school attainment vs college graduate or above (material OR = 2.22, 95% CI = 1.45 to 3.42, psychological OR = 1.75, 95% CI = 1.18 to 2.62, and coping/behavioral OR = 2.05, 95% CI = 1.38 to 3.06). Myocardial infarction, peripheral neuropathy, subsequent neoplasm, seizure, stroke, reproductive disorders, amputation, and upper gastrointestinal disease were associated with higher material hardship (all P < .05). Hardship across three domains was associated with somatization, anxiety and depression (all P < .001), suicidal ideation (all P < .05), and difficulty in retirement planning (all P < .001). Survivors with hardship had statistically significantly lower HRQOL (all P < .001), sensation abnormality (all P < .001), and pulmonary (all P < .05) and cardiac (all P < .05) symptoms., Conclusions: A substantial proportion of adult survivors of childhood cancer experienced financial hardship. Vulnerable sociodemographic status and late effects were associated with hardship. Survivors with financial hardship had an increased risk of symptom prevalence and impaired HRQOL., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Survivors of childhood cancer report poor health-related quality of life (HRQOL). Modifiable lifestyle factors such as nutrition and physical activity represent opportunities for interventions to improve HRQOL., Methods: The authors examined the association between modifiable lifestyle factors and HRQOL among 2480 adult survivors of childhood cancer in the St. Jude Lifetime Cohort Study. Dietary intake, physical activity, cigarette smoking, and alcohol consumption were assessed through questionnaires. Weight and height were measured in the clinic. HRQOL was evaluated using the Medical Outcome Study 36-Item Short Form Survey. The physical component summary (PCS), mental component summary (MCS), and 8 domain scores of HRQOL were calculated. Multivariable linear regression models were used to estimate regression coefficients (β) associated with HRQOL differences., Results: Being physically active (PCS β = 3.10; and MCS β = 1.48) was associated with higher HRQOL whereas current cigarette smoking (PCS β = -2.30; and MCS β = -6.49) and obesity (body mass index ≥30 kg/m 2 ) (PCS β = -3.29; and MCS β = -1.61) were associated with lower HRQOL in both the physical and mental domains. Better diet (Healthy Eating Index-2015) was associated with higher physical HRQOL (PCS β = 1.79). Moderate alcohol consumption was associated with higher physical (PCS β = 1.14) but lower mental (MCS β = -1.13) HRQOL (all P <.05). Adherence to multiple healthy lifestyle factors demonstrated a linear trend with high scores in both physical and mental HRQOL (highest vs lowest adherence: PCS β = 7.60; and MCS β = 5.76 [P for trend, <.0001])., Conclusions: The association between healthy lifestyle factors and HRQOL is cumulative, underscoring the importance of promoting multiple healthy lifestyles to enhance HRQOL in long-term survivors of childhood cancer., (© 2018 American Cancer Society.)

Purpose Beyond survival, achieving independence is a primary goal for adult survivors of pediatric CNS tumors. However, the prevalence of and risk factors for failure to achieve independence, assessed with multiple concurrent indicators, have not been examined. Patients and Methods Functional and social independence was assessed in 306 survivors (astrocytoma [n = 130], medulloblastoma [n = 77], ependymoma [n = 36], and other [n = 63]; median current age, 25.3 years [range, 18.9 to 53.1 years]; time since diagnosis, 16.8 years [range, 10.6 to 41.8 years]). Six observed indicators were used to identify latent classes of independence, which included employment, living independently, assistance with personal care, assistance with routine needs, obtaining a driver's license, and marital status. Physical performance impairments were defined as scores < 10th percentile on measures of aerobic capacity, strength, flexibility, balance, mobility, and adaptive function. Multinomial logistic regression estimated odds ratios (ORs) and 95% CIs were calculated for associations of disease/treatment exposures and impairments in physical performance with nonindependence. Results Three classes of independence were identified as independent (40%), moderately independent (34%), and nonindependent (26%). In multivariable models, craniospinal irradiation (OR, 4.20; 95% CI, 1.69 to 10.44) and younger age at diagnosis (OR, 1.24; 95% CI, 1.14 to 1.35) were associated with risk of nonindependence versus independence. Beyond impaired IQ, limitations in aerobic capacity (OR, 5.47; 95% CI, 1.78 to 16.76), flexibility (OR, 3.66; 95% CI, 1.11 to 12.03), and adaptive physical function (OR, 11.54; 95% CI, 3.57 to 37.27) were associated with nonindependence versus independence. Nonindependent survivors reported reduced physical but not mental health-related quality of life compared with independent survivors. Conclusion Sixty percent of survivors of pediatric CNS tumors do not achieve complete independence as adults. Reduction in intensity of primary therapies and interventions that target physical performance and adaptive deficits may help survivors to achieve greater independence.

Background: Children with non-Hodgkin lymphoma (NHL) undergo treatment with central nervous system-directed therapy, the potentially neurotoxic effects of which have not been reported in NHL survivors., Methods: NHL survivors (n = 187) participating in the St. Jude Lifetime Cohort who were 10 or more years from their diagnosis and were 18 years old or older underwent neurocognitive, emotional distress (Brief Symptom Inventory 18), and health-related quality of life (HRQOL) assessments (36-Item Short Form Health Survey). Age-adjusted z scores were compared with community controls (n = 181) and normative data. Treatment exposures were abstracted from medical records. Models adjusted for the age, sex, and time from diagnosis were used to calculate the risk of impairment., Results: The mean ages at evaluation were similar for the survivors and the controls (35.7 ± 8.9 vs 35.5 ± 11.0 years; P = .86). Survivors were 25.2 ± 8.8 years from their diagnosis: 43 (23%) received cranial radiation, 70 (37%) received high-dose methotrexate, 40 (21%) received high-dose cytarabine, and 151 (81%) received intrathecal chemotherapy. Survivors' intelligence and attention were within normal limits; however, their memory, executive function, processing speed, and academics were impaired in comparison with both population norms and community controls (P values < .05). Treatment-related exposures were not associated with neurocognitive function; however, neurocognitive impairment was associated with lower educational attainment, unemployment, and occupational status (P values < .03). Slower processing speed and worse self-reported executive function were associated with symptoms of depression (P values ≤ .003) and poorer HRQOL (P values < .05)., Conclusions: Adult survivors of childhood NHL experience impaired neurocognitive function, which is associated with lower social attainment and poor HRQOL. Early-detection and intervention strategies are recommended. Cancer 2017. © 2017 American Cancer Society., (© 2017 American Cancer Society.)

Background: To compare associations of symptom prevalence, chronic conditions, and health-related quality of life (HRQOL) between cancer survivors and non-cancer individuals using the U.S. National Health Interview Survey. Methods: Study samples comprised 604 survivors and 6,166 non-cancer individuals. Symptoms included sensation abnormality, pain, fatigue, cognitive disturbance, depression, and anxiety. Physical and mental HRQOL was measured by the Patient-Reported Outcomes Measurement Information System. Results: Compared with non-cancer individuals, survivors had higher prevalence in sensation abnormality (OR = 2.4; 95% CI = 1.9 to 3.0), pain (OR = 2.1; 95% CI = 1.7 to 2.6), fatigue (OR = 1.4; 95% CI = 1.1 to 1.8), and decremented physical HRQOL (difference = -3.7; 95% CI = -4.7 to -2.6). The prevalence of individual symptoms was significantly associated with decremented physical HRQOL [range = -5.9 (anxiety) to -8.9 (pain)] and mental HRQOL [range = -4.7 (sensation) to -8.4 (depression)]. The association between cancer experience and physical and mental HRQOL was chiefly explained by the prevalence of six symptoms and presence of chronic conditions. Pain (β = -4.0; 95% CI = -4.5 to -3.6) and ≥2 chronic conditions (β = -9.2; 95% CI = -10.2 to -8.2) significantly decremented physical HRQOL. Depression (β = -5.2; 95% CI = -5.8 to -4.6) and ≥2 chronic conditions (β = -3.3; 95% CI = -4.4 to -2.3) significantly decremented mental HRQOL. Conclusions: Cancer survivors experience more symptom burden than non-cancer individuals, which is associated with more chronic conditions and impaired HRQOL. Impacts: Interventions to manage symptom prevalence especially for older cancer survivors and survivors with more chronic conditions may improve their HRQOL outcomes. Cancer Epidemiol Biomarkers Prev; 26(7); 1124-32. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Research has shown that self-esteem and hopefulness are positively related among female childhood cancer survivors (CCS) and contribute to their health-related quality of life (HRQOL). HRQOL remains a significant outcome of treatment for CCS. This study examined the relationships among self-esteem, hopefulness, and HRQOL in young adult female CCS to inform the development of evidence-based practice guidelines for pediatric oncology nursing practice. An online survey was conducted with a sample of young adult female CCS from 58 treatment centers across the United States at 4 time points: at baseline and at 6 weeks, 3 months, and 6 months after initial measurement time. The relationships between self-esteem, hopefulness, and HRQOL were statistically significant (Time 1, P = .05; Times 2, 3, and 4, P = .01) across all measurement times. These findings identify hopefulness and self-esteem as determinants of HRQOL and suggest that caring practices among pediatric oncology nurses that support psychosocial adjustment through promoting self-esteem and hopefulness have the potential to support HRQOL among young adult female CCS. These outcomes support the development of evidence-based practice guidelines to influence HRQOL outcomes among these survivors.

Health utility, a summary measure of quality of life, has not been previously used to compare outcomes among childhood cancer survivors and individuals without a cancer history. We estimated health utility (0, death; 1, perfect health) using the Short Form-6D (SF-6D) in survivors (n = 7105) and siblings of survivors (n = 372) (using the Childhood Cancer Survivor Study cohort) and the general population (n = 12 803) (using the Medical Expenditures Panel Survey). Survivors had statistically significantly lower SF-6D scores than the general population (mean = 0.769, 95% confidence interval [CI] = 0.766 to 0.771, vs mean = 0.809, 95% CI = 0.806 to 0.813, respectively, ITALIC! P< .001, two-sided). Young adult survivors (age 18-29 years) reported scores comparable with general population estimates for people age 40 to 49 years. Among survivors, SF-6D scores were largely determined by number and severity of chronic conditions. No clinically meaningful differences were identified between siblings and the general population (mean = 0.793, 95% CI = 0.782 to 0.805, vs mean = 0.809, 95% CI = 0.806 to 0.813, respectively). This analysis illustrates the importance of chronic conditions on long-term survivor quality of life and provides encouraging results on sibling well-being. Preference-based utilities are informative tools for outcomes research in cancer survivors., (© The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Background: Increased headache prevalence was recently reported in survivors of childhood ALL. Headache sub types, related morbidity, and effect on quality of life has not been reported thus far., Objective: To study headache prevalence and type, related disability, and quality of life in a cohort of childhood acute lymphoblastic leukemia (ALL) survivors., Methods: Childhood ALL survivors in at least 1-year of remission and 5 years from diagnosis completed questionnaires and were evaluated by a neurologist. Disability was evaluated with Pediatric Migraine Disability Assessment scale and the Short Form-36 Health Survey assessed quality of life., Results: Thirty nine of 72 (54%) females and 37 of 90 (41%) males reported headaches. Median time from ALL diagnosis to first headache was 5.2 years and median age at headache onset was 10.1 years in 76 participants with headache. Migraine headaches were diagnosed in 51 (31%) and episodic tension-type headaches in 49 (30%); migraine and tension-type headaches co-existed in 24 (15%) and 18 (11%) participants had chronic daily headaches. Fatigue was associated with migraine headache while hypertension and female gender associated with tension type headache. Headache-related disability was mild in 22 (29%), moderate in 7 (9%), and severe in 5 (7%) survivors, and was absent in the remaining 42 (55%) survivors with headache. Both migraine and tension type headaches associated with reduced mental component scores, while headache related disability associated with a reduced physical component scores., Conclusions: Headaches are common in ALL survivors but only a minority has significant disability or impairment of quality of life., (Copyright © 2014 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.)

Adult survivors of childhood brain tumors experience multiple, significant, lifelong deficits as a consequence of their malignancy and therapy. Current survivorship literature documents the substantial impact such impairments have on survivors' physical health and quality of life. Psychosocial reports detail educational, cognitive, and emotional limitations characterizing survivors as especially fragile, often incompetent, and unreliable in evaluating their circumstances. Anecdotal data suggest some survivors report life experiences similar to those of healthy controls. The aim of our investigation was to determine whether life satisfaction in adult survivors of childhood brain tumors differs from that of healthy controls and to identify potential predictors of life satisfaction in survivors. This cross-sectional study compared 78 brain tumor survivors with population-based matched controls. Chi-square tests, t tests, and linear regression models were used to investigate patterns of life satisfaction and identify potential correlates. Results indicated that life satisfaction of adult survivors of childhood brain tumors was similar to that of healthy controls. Survivors' general health expectations emerged as the primary correlate of life satisfaction. Understanding life satisfaction as an important variable will optimize the design of strategies to enhance participation in follow-up care, reduce suffering, and optimize quality of life in this vulnerable population., (© 2014 by Association of Pediatric Hematology/Oncology Nurses.)

Purpose: We investigated the association between prevalence of symptoms and health-related quality of life (HRQOL) in adult survivors of childhood cancer enrolled in the St Jude Lifetime Cohort study., Methods: Eligibility criteria include childhood malignancy treated at St Jude, survival ≥ 10 years from diagnosis, and current age ≥ 18 years. Study participants were 1,667 survivors (response rate = 65%). Symptoms were self-reported by using a comprehensive health questionnaire and categorized into 12 classes: cardiac; pulmonary; motor/movement; pain in head; pain in back/neck; pain involving sites other than head, neck, and back; sensation abnormalities; disfigurement; learning/memory; anxiety; depression; and somatization. HRQOL was measured by using physical/mental component summary (PCS/MCS) and six domain scores of the Medical Outcomes Study 36-Item Short-Form Health Survey. Multivariable regression analysis was performed to investigate associations between symptom classes and HRQOL. Cumulative prevalence of symptom classes in relation to time from diagnosis was estimated., Results: Pain involving sites other than head, neck and back, and disfigurement represented the most frequent symptom classes, endorsed by 58.7% and 56.3% of survivors, respectively. Approximately 87% of survivors reported multiple symptom classes. Greater symptom prevalence was associated with poorer HRQOL. In multivariable analysis, symptom classes explained up to 60% of the variance in PCS and 56% of the variance in MCS; demographic and clinical variables explained up to 15% of the variance in PCS and 10% of the variance in MCS. Longer time since diagnosis was associated with higher cumulative prevalence in all symptom classes., Conclusion: A large proportion of survivors suffered from many symptom classes, which was associated with HRQOL impairment.

Purpose: Examine the construct validity, stability, internal consistency, and item-response performance of a self-report health needs assessment for adult survivors of childhood cancer., Methods: A 190-item mailed survey was completed by 1,178 randomly selected (stratified on age, diagnosis, time since diagnosis) Childhood Cancer Survivor Study participants (mean age, 39.66 [SD 7.71] years; time since diagnosis, 31.60 [SD 4.71] years). Minorities and rural residents were oversampled at a 2:1 ratio., Results: The final instrument included 135 items comprising nine unidimensional subscales (Psycho-emotional, Health System Concerns, Cancer-Related Health Information, General Health, Survivor Care and Support, Surveillance, Coping, Fiscal Concerns, and Relationships). Confirmatory factor analysis (n = 1,178; RMSEA = 0.020; 90 % CI = 0.019-0.020; CFI = 0.956; TLI = 0.955) and person-item fit variable maps established construct validity. Across subscales, Cronbach's alpha was 0.94-0.97, and the 4-week test-retest correlations were 0.52-0.91. In a Rasch analysis, item reliability was 0.97-0.99, person reliability was 0.80-0.90, and separation index scores were 2.00-3.01. Significant subscale covariates of higher need levels included demographics, diagnosis, and treatment exposures., Conclusions: The Childhood Cancer Survivor Study Needs Assessment Questionnaire (CCSS-NAQ) is reliable and construct-valid, has strong item-response properties, and discriminates need levels., Implications for Cancer Survivors: The CCSS-NAQ potentially can be used to: (1) directly assess adult childhood cancer survivors' self-reported health-related needs, (2) identify individuals or subgroups with higher-level needs, (3) inform prevention and direct intervention strategies, and (4) facilitate prioritization of health-care resource allocation.

Background: To facilitate prospective medical assessment of adults surviving pediatric malignancies and advance knowledge about long-term childhood cancer survivor health, St. Jude Children's Research Hospital (SJCRH) is establishing a lifetime cohort of survivors., Methods: Eligibility criteria for inclusion in the St. Jude Lifetime Cohort (SJLIFE) study include: (1) diagnosis of childhood malignancy treated at SJCRH; (2) survival ≥ 10 years from diagnosis; and (3) current age ≥ 18 years. Three levels of participation are offered: (1) comprehensive evaluation on SJCRH campus; (2) limited home evaluation; or (3) completion of health surveys only. A systematic recruitment structure based upon blocks of 50 patients initially focused on leukemia and lymphoma survivors and patients eligible for pilot studies., Results: As of January 1, 2010, 1,625 (42%) of 3,900 eligible ≥ 10-year survivors have been contacted. Among the first 1,000 potentially eligible survivors selected for recruitment, 971 were subsequently confirmed to fulfill eligibility criteria. To date, 898/971 (92.5%) have been successfully contacted of whom 825 (91.8%) have agreed to participate. Among participants, 88.6% agreed to comprehensive medical evaluation, 0.4% limited local evaluation, and 11.0% survey only. Anticipated minimum overall participation rate for medical evaluation is 75.3% (731/971). Comparison of those contacted who agreed versus declined to participate revealed a greater proportion of males who declined participation (P = 0.001)., Conclusions: Early results of the SJLIFE study support its feasibility to recruit aging childhood cancer survivors to research investigations evaluating late health outcomes by medical assessments., (Copyright © 2010 Wiley-Liss, Inc.)

Introduction: The use of rehabilitation services to address musculoskeletal, neurological and cardiovascular late effects among childhood cancer survivors could improve physical function and health-related quality-of-life (HRQL). We describe physical therapy (PT) and chiropractic utilization among childhood cancer survivors and their association with HRQL., Methods: The sample included 5+ year survivors from the Childhood Cancer Survivor Study (N = 9,289). Questions addressing use of PT or chiropractic services and HRQL (Medical Outcomes Survey Short Form (SF-36)) were evaluated. Multivariable regression models compared PT and/or chiropractic utilization between survivors and siblings, and by diagnosis, treatment and demographic characteristics; associations between chronic disease, PT/chiropractic use, and HRQL were similarly evaluated., Results: Survivors were not more likely to use PT (OR 1.0; 95% CI 0.8-1.2) or chiropractic (OR 0.8; 95% CI 0.7-1.0) services than siblings. More survivors reported using chiropractic (12.4%) than PT (9.2%) services. Older age and having health insurance were associated with utilization of either PT or chiropractic services. Grade 3-4 chronic conditions and a CNS tumor or sarcoma history were associated with PT but not with chiropractic service utilization. Survivors with musculoskeletal (OR 1.8; 95% CI 1.1-2.9), neurological (OR 3.4; 95% CI 1.6-6.9), or cardiovascular (OR 3.3; 95% CI 1.6-6.9) chronic conditions who used PT/chiropractic services were more likely to report poor physical health than survivors who did not use services., Conclusions: The reported prevalence of PT/chiropractic among survivors is consistent with that reported by siblings. Severity of late effects is associated with service use and with reporting poor physical health., Implications for Cancer Survivors: Long-term childhood cancer survivors do not appear to utilize rehabilitation services to optimize physical function and support increased HRQL.

Background: Despite interest in the well-being of adult survivors of childhood rhabdomyosarcoma (RMS), few studies have examined their health-related quality of life (HRQOL). This study evaluated physical and social aspects of HRQOL among long-term childhood RMS survivors relative to a sibling comparison group, and assessed whether physical impairment among RMS survivors adversely affected their ability to achieve adult life goals., Methods: Using baseline data from the Childhood Cancer Survivor Study, we evaluated self-reported physical impairment and social adaptation among 417 survivors of childhood RMS and 2685 siblings > or =18 years of age at survey completion., Results: Survivors were more likely than siblings to report physical impairment, characterized by: at least one medically diagnosed condition, limitations in the performance of routine activities, a health-related inability to work or attend school, cancer-related pain. Survivors were less likely than siblings to have completed high school, ever worked a job, or ever been married. The odds of completing high school were lower among survivors with performance limitations, a health-related inability to work or attend school, or moderate to high levels of cancer-related pain. Survivors who reported cancer-related pain had an increased likelihood of ever being married., Conclusions: The majority of adult survivors of pediatric RMS are successful in attaining adult life goals despite higher reported occurrence of physical impairment than their sibling counterparts. Additional studies are needed to advance our understanding of other aspects of HRQOL in this population of pediatric cancer survivors., (Copyright 2006 John Wiley & Sons, Ltd.)

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.

Background Childhood cancer survivors are at high risk for morbidity and mortality and poor patient-reported outcomes, typically health-related quality of life (HRQOL). However, associations between DNA methylation–based aging biomarkers and HRQOL have not been evaluated. Methods DNA methylation was generated with Infinium EPIC BeadChip on blood-derived DNA (median for age at blood draw = 34.5 years, range = 18.5-66.6 years), and HRQOL was assessed with age at survey (mean = 32.3 years, range = 18.4-64.5 years) from 2206 survivors in the St Jude Lifetime Cohort. DNA methylation–based aging biomarkers, including epigenetic age using multiple clocks (eg, GrimAge) and others (eg, DNAmB2M: beta-2-microglobulin; DNAmADM: adrenomedullin), were derived from the DNAm Age Calculator (https://dnamage.genetics.ucla.edu). HRQOL was assessed using the Medical Outcomes Study 36-Item Short-Form Health Survey to capture 8 domains and physical and mental component summaries. General linear models evaluated associations between HRQOL and epigenetic age acceleration (EAA; eg, EAA_GrimAge) or other age-adjusted DNA methylation–based biomarkers (eg, ageadj_DNAmB2M) after adjusting for age at blood draw, sex, cancer treatments, and DNA methylation–based surrogate for smoking pack-years. All P values were 2-sided. Results Worse HRQOL was associated with greater EAA_GrimAge (physical component summaries: β = -0.18 years, 95% confidence interval [CI] = -0.251 to -0.11 years; P  = 1.85 × 10−5; and 4 individual HRQOL domains), followed by ageadj_DNAmB2M (physical component summaries: β = -0.08 years, 95% CI = -0.124 to -0.037 years; P  = .003; and 3 individual HRQOL domains) and ageadj_DNAmADM (physical component summaries: β = -0.082 years, 95% CI = -0.125 to -0.039 years; P  = .002; and 2 HRQOL domains). EAA_Hannum (Hannum clock) was not associated with any HRQOL. Conclusions Overall and domain-specific measures of HRQOL are associated with DNA methylation measures of biological aging. Future longitudinal studies should test biological aging as a potential mechanism underlying the association between poor HRQOL and increased risk of clinically assessed adverse health outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: This cross-sectional study analyzed how multilevel social factors affect patient-reported outcomes in children under 18 who survived cancer. Study participants include 293 pairs of these survivors who received survivorship care at a U.S.-based comprehensive cancer center between 2017 and 2018 and their primary caregivers. Findings indicate that higher caregiver anxiety is linked to worse depression, stress, fatigue, sleep problems, and lower positive affect in survivors of pediatric cancer. The study also found that family conflicts are associated with sleep issues in childhood cancer survivors. Furthermore, survivors living in socioeconomically deprived areas experience poorer sleep quality, and those residing in environments with high physical deprivation experience more psychological stress and fatigue, alongside reduced positivity and mobility. These results highlight the significant impact of parental, familial, and neighborhood factors on a range of patient-reported outcomes among young cancer survivors, suggesting these social factors as crucial targets for intervention. In this study, the social determinants of patient-reported outcomes (PROs) in young survivors of childhood cancer aged <18 years are researched. This cross-sectional study investigated social determinants associated with poor PROs among young childhood cancer survivors. We included 293 dyads of survivors receiving treatment at St. Jude Children's Research Hospital who were <18 years of age during follow-up from 2017 to 2018 and their primary caregivers. Social determinants included family factors (caregiver-reported PROs, family dynamics) and county-level deprivation (socioeconomic status, physical environment via the County Health Rankings & Roadmaps). PROMIS measures assessed survivors' and caregivers' PROs. General linear regression tested associations of social determinants with survivors' PROs. We found that caregivers' higher anxiety was significantly associated with survivors' poorer depression, stress, fatigue, sleep issues, and reduced positive affect (p < 0.05); caregivers' sleep disturbances were significantly associated with lower mobility in survivors (p < 0.05). Family conflicts were associated with survivors' sleep problems (p < 0.05). Residing in socioeconomically deprived areas was significantly associated with survivors' poorer sleep quality (p < 0.05), while higher physical environment deprivation was associated with survivors' higher psychological stress and fatigue and lower positive affect and mobility (p < 0.05). Parental, family, and neighborhood factors are critical influences on young survivors' quality of life and well-being and represent new intervention targets. [ABSTRACT FROM AUTHOR]

The article examines the effects of financial toxicity on childhood cancer survivors. Topics discussed include individual-level drivers of financial toxicity, estimated childhood cancer survivors in the U.S. who potentially face decades more of indirect costs related to their childhood cancer, and multilevel interventions for financial toxicity.

Simple Summary: Patient-reported outcome measures (PROMs) are a useful way to assess the subjective experiences of health-related quality of life, functional status, symptoms, and other outcomes in childhood cancer survivors. In survivorship care, PROMs can be used to monitor health status and inform medical decision making. This article provides 10 important considerations for clinicians when they are assessing patient-reported outcomes for childhood cancer survivors. From choosing the right measure to selecting a strategy for clinical response, the purpose of these considerations is to support clinicians in implementing PROMs in their practice while keeping in mind some of the practical barriers and solutions of using PROMs with childhood cancer survivors. We end with an example of a framework for integrating PROMs into the clinical workflow that uses cutting-edge technologies (e.g., mHealth, natural language processing, and machine learning) to minimize interruptions to the clinical workflow and maximize the powerful utility of PROMs in cancer survivorship care. Patient-reported outcome measures (PROMs) are subjective assessments of health status or health-related quality of life. In childhood cancer survivors, PROMs can be used to evaluate the adverse effects of cancer treatment and guide cancer survivorship care. However, there are barriers to integrating PROMs into clinical practice, such as constraints in clinical validity, meaningful interpretation, and technology-enabled administration of the measures. This article discusses these barriers and proposes 10 important considerations for appropriate PROM integration into clinical care for choosing the right measure (considering the purpose of using a PROM, health profile vs. health preference approaches, measurement properties), ensuring survivors complete the PROMs (data collection method, data collection frequency, survivor capacity, self- vs. proxy reports), interpreting the results (scoring methods, clinical meaning and interpretability), and selecting a strategy for clinical response (integration into the clinical workflow). An example framework for integrating novel patient-reported outcome (PRO) data collection into the clinical workflow for childhood cancer survivorship care is also discussed. As we continuously improve the clinical validity of PROMs and address implementation barriers, routine PRO assessment and monitoring in pediatric cancer survivorship offer opportunities to facilitate clinical decision making and improve the quality of survivorship care. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to determine the impact of seizure‐related factors on neurocognitive, health‐related quality of life (HRQOL), and social outcomes in survivors of childhood cancer. Methods: Survivors of childhood cancer treated at St. Jude Children's Hospital (n = 2022; 48.3% female; median age, 31.5 years; median time since diagnosis, 23.6 years) completed neurocognitive testing and questionnaires. The presence, severity, resolution, and treatment history of seizures were abstracted from medical records. Adjusting for the age at diagnosis, sex, and prior cancer therapy, multivariable models examined the impact of seizures on neurocognitive and HRQOL outcomes. Mediation analyses were conducted for social outcomes. Results: Seizures were identified in 232 survivors (11.5%; 29.9% of survivors with central nervous system [CNS] tumors and 9.0% of those without CNS tumors). In CNS tumor survivors, seizures were associated with poorer executive function and processing speed (P <.02); in non‐CNS tumor survivors, seizures were associated with worse function in every domain (P <.05). Among non‐CNS survivors, seizure severity was associated with worse processing speed (P =.023), and resolution was associated with better executive function (P =.028) and attention (P =.044). In CNS survivors, seizure resolution was associated with improved attention (P =.047) and memory (P <.02). Mediation analysis revealed that the impact of seizures on social outcomes was mediated by neurocognitive function. Conclusions: Seizures in cancer survivors adversely affect long‐term functional and psychosocial outcomes independently of cancer therapy. The resolution of seizure occurrence is associated with better outcomes. Seizure severity is associated with poorer outcomes and should be a focus of clinical management and patient education. Adult survivors of childhood cancer are at risk for poorer cognitive, health‐related quality of life, and social outcomes. Seizure frequency, independently of the underlying etiology, is associated with poorer outcomes in non–brain tumor survivors, and this implies that they may be a more vulnerable population with a lower threshold for impact from seizures of any severity. [ABSTRACT FROM AUTHOR]

Background: Although survivors of childhood cancer are at risk of chronic pain, the impact of pain on daily functioning is not well understood. Methods: A total of 2836 survivors (mean age, 32.2 years [SD, 8.5 years]; mean time since diagnosis, 23.7 years [SD, 8.2 years]) and 343 noncancer community controls (mean age, 35.5 years [SD, 10.2 years]) underwent comprehensive medical, neurocognitive, and physical performance assessments, and completed measures of pain, health‐related quality of life (HRQOL), and social functioning. Multinomial logistic regression models, using odds ratios and 95% confidence intervals (95% CIs), examined associations between diagnosis, treatment exposures, chronic health conditions, and pain. Relative risks (RRs) between pain and neurocognition, physical performance, social functioning, and HRQOL were examined using modified Poisson regression. Results: Approximately 18% of survivors (95% CI, 16.1%‐18.9%) versus 8% of controls (95% CI, 5.0%‐10.9%) reported moderate to very severe pain with moderate to extreme daily interference (P <.001). Severe and life‐threatening chronic health conditions were associated with an increased likelihood of pain with interference (odds ratio, 2.03; 95% CI, 1.62‐2.54). Pain with daily interference was found to be associated with an increased risk of impaired neurocognition (attention: RR, 1.88 [95% CI, 1.46‐2.41]; and memory: RR, 1.65 [95% CI, 1.25‐2.17]), physical functioning (aerobic capacity: RR, 2.29 [95% CI, 1.84‐2.84]; and mobility: RR, 1.71 [95% CI, 1.42‐2.06]), social functioning (inability to hold a job and/or attend school: RR, 4.46 [95% CI, 3.45‐5.76]; and assistance with routine and/or personal care needs: RR, 5.64 [95% CI, 3.92‐8.10]), and HRQOL (physical: RR, 6.34 [95% CI, 5.04‐7.98]; and emotional: RR, 2.83 [95% CI, 2.28‐3.50]). Conclusions: Survivors of childhood cancer are at risk of pain and associated functional impairments. Survivors should be screened routinely for pain and interventions targeting pain interference are needed. Adult survivors of childhood cancer are at an increased risk of moderate to very severe pain compared with community controls. In long‐term survivors, pain significantly interferes with multiple aspects of daily functioning. [ABSTRACT FROM AUTHOR]

Background: To the authors' knowledge, few studies to date have examined long-term neurocognitive outcomes in survivors of childhood soft-tissue sarcoma.Methods: A total of 150 survivors (41% of whom were female with a mean current age of 33 years [SD, 8.9 years] and a time since diagnosis of 24 years [SD, 8.7 years]) and 349 community controls (56% of whom were female with a mean current age of 35 years [SD, 10.2 years]) completed comprehensive neuropsychological testing, echocardiography, electrocardiography, pulmonary function tests, endocrine evaluation, and physical examination. Patient-reported outcomes of health-related quality of life (HRQOL) and social attainment were collected. Survivors were compared with norms and controls on neurocognitive outcomes using general linear models, and on HRQOL and social attainment using modified Poisson models. The impacts of treatment and chronic health conditions on outcomes were examined using multivariable general linear models (effect size was expressed as unstandardized β estimates that reflected the unit of change from a mean of 0 and an SD of 1) and modified Poisson models (effect size expressed as relative risks).Results: Compared with controls and population norms, survivors demonstrated lower performance on measures of verbal reasoning (mean z score, -0.45 [SD, 1.15]; P < .001) mathematics (mean z score, -0.63 [SD, 1.07]; P < .001), and long-term memory (mean z score, -0.37 [SD, 1.14]; P < .001). Cumulative anthracycline exposure (per 100 mg/m2 ) was found to be associated with poorer verbal reasoning (β = -0.14 z scores; P = .04), reading (β = -0.09 z score; P = .04), and patient-reported vitality (relative risk, 1.32; 95% CI, 1.09-1.59). Neurologic and neurosensory chronic conditions were associated with poorer mathematics (neurologic conditions: β = -0.63 z score [P = 0.02]; and hearing impairment: β = -0.75 z scores [P < 0.01]). Better cognitive performance was associated with higher social attainment.Conclusions: Long-term survivors of soft-tissue sarcoma are at risk of neurocognitive problems and poor HRQOL associated with anthracycline treatment and chronic health conditions. [ABSTRACT FROM AUTHOR]

Background: Survivors of childhood cancer are at risk of neurocognitive impairment, emotional distress, and poor health-related quality of life (HRQOL); however, the effect of race/ethnicity is understudied. The objective of this study was to identify race/ethnicity-based disparities in neurocognitive, emotional, and HRQOL outcomes among survivors of childhood cancer.Methods: Self-reported measures of neurocognitive function, emotional distress (the Brief Symptom Inventory-18), and HRQOL (the Medical Outcomes Study Short Form-36 health survey) were compared between minority (Hispanic, n = 821; non-Hispanic black [NHB], n = 600) and non-Hispanic white (NHW) (n = 12,287) survivors from the Childhood Cancer Survivor Study (median age, 30.9 years; range, 16.0-54.1 years). By using a sample of 3055 siblings, the magnitude of same-race/same-ethnicity survivor-sibling differences was compared between racial/ethnic groups, adjusting for demographic and treatment characteristics and current socioeconomic status (SES).Results: No clear pattern of disparity in neurocognitive outcomes by race/ethnicity was observed. The magnitude of the survivor-sibling difference in the mean score for depression was greater in Hispanics than in NHWs (3.59 vs 1.09; P = .004). NHBs and Hispanics had greater survivor-sibling differences in HRQOL than NHWs for mental health (NHBs: -5.78 vs -0.69; P = .001; Hispanics: -3.87 vs -0.69; P = .03), and social function (NHBs: -7.11 vs -1.47; P < .001; Hispanics: -5.33 vs -1.47; P = .001). NHBs had greater survivor-sibling differences in physical subscale scores for HRQOL than NHWs. In general, the findings were not attenuated by current SES.Conclusions: Although no pattern of disparity in neurocognitive outcomes was observed, differences across many HRQOL outcomes among minorities compared with NHWs, not attenuated by current SES, were identified. This suggests that further research into environmental and sociocultural factors during and immediately after treatment is needed. [ABSTRACT FROM AUTHOR]

Objective: How family environment and parental factors affect health status and symptoms in childhood cancer survivors is understudied. We examined the influence of family cohesion, parent distress, and overprotection on child symptom burden and health-related quality of life (HRQOL) and family strain in survivors of childhood acute lymphoblastic leukemia.Methods: Parents of 213 children treated with chemotherapy only completed a survey when survivors were at least 5-year postdiagnosis. Family Environment Scale, Brief Symptom Inventory-18, Parent Protection Scale, Pediatric Quality of Life Inventory, and Impact on Family were used to assess family cohesion, parental distress, overprotection, child symptom burden and HRQOL, and family strain, respectively. Path analysis was conducted to quantify effects of family cohesion on family strain through parental distress, overprotection, child symptoms, and HRQOL.Results: Lower family cohesion (β = 0.06, 95% CI, 0.01-0.13), higher parental distress (β = 0.35, 95% CI, 0.20-0.45), and overprotection (β = 0.17, 95% CI, 0.01-0.32) were associated with more child symptom burden. More symptom burden were associated with poorer child HRQOL (β = 0.66, 95% CI, 0.57-0.75), which in turn was associated with more family strain (β = 0.11, 95% CI, 0.01-0.22). Lower maternal education was associated with overprotection (β = -0.23, 95% CI, -0.33 to -0.12), more child symptoms (β = -0.30, 95% CI, -0.41 to -0.16), poorer child HRQOL (β = -0.36, 95% CI, -0.46 to -0.21), and more family strain (β = -0.15, 95% CI, -0.23 to -0.08).Conclusions: Family and parental factors contributed to health outcomes of childhood acute lymphoblastic leukemia survivors. Interventions to enhance family cohesion, decrease parental distress and overprotection, and ameliorate child symptoms may improve family functioning. [ABSTRACT FROM AUTHOR]

Objective: To examine the potential mediating role of body image dissatisfaction on the association between treatment-related scarring/disfigurement and psychological distress in adult survivors of childhood cancer.Methods: Participants included 1714 adult survivors of childhood cancer (mean [SD] age at evaluation = 32.4 [8.0] years, time since diagnosis = 24.1 [8.1] years) enrolled in the St. Jude Lifetime Cohort Study. Survivors completed measures of body image, emotional distress, and posttraumatic stress symptoms (PTSS). Body image dissatisfaction (BID) was categorized into 2 groups (cancer-related and general) based on factor analysis. Using causal mediation analysis, we estimated the proportion of psychological distress associated with treatment-related scarring/disfigurement that could be eliminated by resolving BID through a hypothetical intervention.Results: Among survivors with scarring/disfigurement of the head, a sizable proportion of the relative excess of psychological distress could be eliminated if BID was successfully treated (males: [cancer-related BID: depression: 63%; anxiety: 100%; PTSS: 52%]; [general BID: depression: 70%; anxiety: 100%; PTSS: 42%]; females: [cancer-related BID: depression: 20%; anxiety; 36%; PTSS: 23%]; [general BID: depression: 32%; anxiety: 87%; PTSS: 38%]). The mediating effect of BID was less pronounced for the association between scarring/disfigurement of the body and psychological distress for both males and females.Conclusions: Body image dissatisfaction mediates the association treatment-related scarring/disfigurement and psychological distress among adult survivors of childhood cancer, particularly among survivors with scarring/disfigurement of the head and male survivors. Successful treatment of body image dissatisfaction has the potential to eliminate a substantial proportion of psychological distress related to scarring/disfigurement among adult survivors of childhood cancer. [ABSTRACT FROM AUTHOR]

Background: Cancer survivors transfused with blood products before reliable screening for hepatitis C virus (HCV) are at risk for infection. This study examined the impact of HCV on neurocognitive function and health-related quality of life (HRQOL) among adult survivors of childhood cancer.Methods: Neurocognitive testing was conducted for 836 adult survivors of childhood cancer (mean age, 35 years [standard deviation, 7.4 years]; time since diagnosis, 29 years [standard deviation, 6.2 years]) who received blood products before universal HCV screening. No differences were observed between confirmed HCV-seropositive survivors (n = 79) and HCV-seronegative survivors (n = 757) in the primary diagnosis or neurotoxic therapies. Multivariate regression models were used to compare functional outcomes between seropositive and seronegative survivors.Results: Compared with seronegative survivors, seropositive survivors demonstrated lower performance on measures of attention (P < .001), processing speed (P = .008), long-term verbal memory (P = .01), and executive function (P = .001). After adjustments for sex, age at diagnosis, and treatment exposures, seropositive survivors had a higher prevalence of impairment in processing speed (prevalence ratio [PR], 1.3; 95% confidence interval [CI], 1.1-1.6) and executive functioning (PR, 1.3; 95% CI, 1.1-1.6). Differences were not associated with the treatment of HCV or the presence of liver cirrhosis. Seropositive survivors reported worse general HRQOL (PR, 1.6; 95% CI, 1.2-2.1), which was associated with the presence of liver cirrhosis (P = .001).Conclusions: Survivors of childhood cancer with a history of HCV infection are at risk for neurocognitive impairment and reduced HRQOL beyond the known risks associated with neurotoxic cancer therapies. Cancer 2017;123:4498-505. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to describe perceptions and associated risk factors of the impact of cancer on functional outcomes, including social relationships, exercise, finances, and religion, among adult survivors of childhood cancer.Methods: Evaluable participants included 3001 adult survivors (mean age, 32.5 years; range, 18.3-63.8 years; 24.1 years from diagnosis; 50.8% male; 84.9% Caucasian) who were enrolled in the St. Jude Lifetime Cohort study. Perceptions of the impact of cancer were assessed using the Brief Cancer Impact Assessment (BCIA). Regression models were used to evaluate risk factors for functional outcomes.Results: The median response on the BCIA was a perception that cancer had minimal impact on the domains assessed. Approximately 33.1% to 46.6% of survivors indicated this response across the 4 subscales, although responses ranged from very positive to very negative impact. Other than diagnosis (with survivors of brain tumors generally indicating a more negative impact of cancer, with subscale estimates of -1.25 for caregiving and finance and -1.01 for social and emotional and an odds ratio of 1.83 for exercise and diet), most variability was because of demographic factors, including sex, age, race, education, and employment.Conclusions: The current findings highlight that many long-term adult survivors perceive minimal impact of childhood cancer on functional aspects of adulthood, including caregiving, finances, exercise, social-emotional relationships, and religion. This suggests that survivors may not be focusing on the influence of likely physical and psychological late effects of their disease in their day-to-day lives. For those who do perceive a negative impact, variability in responses suggests that there are of survivors who may benefit from interventions focused on the achievement of functional goals. Cancer 2017;123:1625-1634. © 2017 American Cancer Society. [ABSTRACT FROM AUTHOR]

Health utility, a summary measure of quality of life, has not been previously used to compare outcomes among childhood cancer survivors and individuals without a cancer history. We estimated health utility (0, death; 1, perfect health) using the Short Form-6D (SF-6D) in survivors (n = 7105) and siblings of survivors (n = 372) (using the Childhood Cancer Survivor Study cohort) and the general population (n = 12 803) (using the Medical Expenditures Panel Survey). Survivors had statistically significantly lower SF-6D scores than the general population (mean = 0.769, 95% confidence interval [CI] = 0.766 to 0.771, vs mean = 0.809, 95% CI = 0.806 to 0.813, respectively, ITALIC! P< .001, two-sided). Young adult survivors (age 18-29 years) reported scores comparable with general population estimates for people age 40 to 49 years. Among survivors, SF-6D scores were largely determined by number and severity of chronic conditions. No clinically meaningful differences were identified between siblings and the general population (mean = 0.793, 95% CI = 0.782 to 0.805, vs mean = 0.809, 95% CI = 0.806 to 0.813, respectively). This analysis illustrates the importance of chronic conditions on long-term survivor quality of life and provides encouraging results on sibling well-being. Preference-based utilities are informative tools for outcomes research in cancer survivors. [ABSTRACT FROM AUTHOR]

Background: Health complications related to childhood cancer may be influenced by risky health behaviors (RHBs), particularly when RHBs co-occur. To the authors' knowledge, only limited information is available describing how RHBs cluster among survivors of childhood cancer and their siblings and the risk factors for co-occurring RHBs.Methods: Latent class analysis was used to identify RHB clusters using longitudinal survey data regarding smoking, alcohol use, and physical activity from adult survivors (4184 survivors) and siblings (1598 siblings) in the Childhood Cancer Survivor Study. Generalized logistic regression was used to evaluate associations between demographic characteristics, treatment exposures, psychological distress, health conditions, and cluster membership.Results: Three RHB clusters were identified: a low-risk cluster, an insufficiently active cluster, and a high-risk cluster (tobacco and risky alcohol use and insufficient activity). Compared with siblings, survivors were more likely to be in the insufficiently active cluster (adjusted odds ratio [ORadj ], 1.17; 95% confidence interval [95% CI], 1.06-1.27) and were less likely to be in the high-risk cluster (ORadj , 0.79; 95% CI, 0.69-0.88). Risk factors for membership in the high-risk cluster included psychological distress (ORadj , 2.76; 95% CI, 1.98-3.86), low educational attainment (ORadj , 7.49; 95% CI, 5.15-10.88), income <$20,000 (ORadj , 2.62; 95% CI, 1.93-3.57), being divorced/separated or widowed (ORadj , 1.36; 95% CI, 1.03-1.79), and limb amputation (ORadj , 1.52; 95% CI, 1.03-2.24). Risk factors for the insufficiently active cluster included chronic health conditions, psychological distress, low education or income, being obese or overweight, female sex, nonwhite race/ethnicity, single marital status, cranial radiation, and cisplatin exposure.Conclusions: RHBs co-occur in survivors of childhood cancer and their siblings. Economic and educational disadvantages and psychological distress should be considered in screening and interventions to reduce RHBs. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2747-2756. © 2016 American Cancer Society. [ABSTRACT FROM AUTHOR]

Treatment with chemotherapy, radiotherapy, or surgery that involves reproductive organs can cause impaired spermatogenesis, testosterone deficiency, and physical sexual dysfunction in male pubertal, adolescent, and young adult cancer survivors. Guidelines for surveillance and management of potential adverse effects could improve cancer survivors' health and quality of life. Surveillance recommendations vary considerably, causing uncertainty about optimum screening practices. This clinical practice guideline recommended by the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCareSurFup Consortium, developed using evidence-based methodology, critically synthesises surveillance recommendations for gonadotoxicity in male childhood, adolescent, and young adult (CAYA) cancer survivors. The recommendations were developed by an international multidisciplinary panel including 25 experts in relevant medical specialties, using a consistent and transparent process. Recommendations were graded according to the strength of underlying evidence and potential benefit gained by early detection and appropriate management. The aim of the recommendations is to enhance evidence-based care for male CAYA cancer survivors. The guidelines reveal the paucity of high-quality evidence, highlighting the need for further targeted research. [ABSTRACT FROM AUTHOR]