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Purpose: Little is known regarding long-term neurocognitive outcomes in osteosarcoma and Ewing sarcoma (EWS) survivors despite potential risk factors. We evaluated associations among treatment exposures, chronic health conditions, and patient-reported neurocognitive outcomes in adult survivors of childhood osteosarcoma and EWS. Methods: Five-year survivors of osteosarcoma (N = 604; median age 37.0 years) and EWS (N = 356; median age 35.0 years) diagnosed at < 21 years from 1970 to 1999, and 697 siblings completed the Childhood Cancer Survivor Study Neurocognitive Questionnaire and reported chronic health conditions, education, and employment. Prevalence of reported neurocognitive difficulties were compared between diagnostic groups and siblings. Modified Poisson regression identified factors associated with neurocognitive difficulties. Results: Osteosarcoma and EWS survivors, vs. siblings, reported higher prevalences of difficulties with task efficiency (15.4% [P = 0.03] and 14.0% [P = 0.04] vs. 9.6%, respectively) and emotional regulation (18.0% [P < 0.0001] and 15.2% [P = 0.03] vs. 11.3%, respectively), adjusted for age, sex, and ethnicity/race. Osteosarcoma survivors reported greater memory difficulties vs. siblings (23.5% vs. 16.4% [P = 0.01]). Comorbid impairment (i.e., ≥ 2 neurocognitive domains) was more prevalent in osteosarcoma (20.0% [P < 0.001]) and EWS survivors (16.3% [P = 0.02]) vs. siblings (10.9%). Neurological conditions were associated with worse task efficiency (RR = 2.17; 95% CI = 1.21–3.88) and emotional regulation (RR = 1.88; 95% CI = 1.01–3.52), and respiratory conditions were associated with worse organization (RR = 2.60; 95% CI = 1.05–6.39) for EWS. Hearing impairment was associated with emotional regulation difficulties for osteosarcoma (RR = 1.98; 95% CI = 1.22–3.20). Patient report of cognitive difficulties was associated with employment but not educational attainment. Conclusions: Survivors of childhood osteosarcoma and EWS are at increased risk for reporting neurocognitive difficulties, which are associated with employment status and appear related to chronic health conditions that develop over time. Implications for Cancer Survivors: Early screening, prevention, and treatment of chronic health conditions may improve/prevent long-term neurocognitive outcomes. [ABSTRACT FROM AUTHOR]

Purpose: To investigate racial/ethnic-related disparities by insurance status in "forgoing needed medical care in the last year due to finances" in childhood cancer survivors. Methods: Our study included 3310 non-Hispanic/Latinx White, 562 non-Hispanic/Latinx Black, and 92 Hispanic/Latinx survivors from the St. Jude Lifetime Cohort Study. Logistic regression analyses, guided by Andersen's Healthcare Utilization Model, were adjusted for "predisposing" (survey age, sex, childhood cancer diagnosis and treatment, and treatment era) and "need" (perceived health status) factors. Additional adjustment for household income/education and chronic health conditions was considered. Results: Risk of forgoing care was highest among non-Hispanic/Latinx Blacks and lowest among Hispanics/Latinxs for each insurance status. Among privately insured survivors, relative to non-Hispanic/Latinx Whites, non-Hispanic/Latinx Blacks were more likely to forgo care (adjusted OR: 1.82, 95% CI: 1.30–2.54): this disparity remained despite additional adjustment for household income/education (adjusted OR: 1.43, 95% CI: 1.01–2.01). In contrast, publicly insured survivors, regardless of race/ethnicity, had similar risk of forgoing care as privately insured non-Hispanic/Latinx Whites. All uninsured survivors had high risk of forgoing care. Additional chronic health condition adjustment did not alter these results. Conclusions: Provision of public insurance to all childhood cancer survivors may diminish racial/ethnic disparities in forgoing care that exist among the privately insured and reduce the risk of forgoing care among uninsured survivors to that of privately insured non-Hispanic/Latinx Whites. Implications for Cancer Survivors: Under public insurance, childhood cancer survivors had low risk of forgoing care, at the similar level to privately insured non-Hispanic/Latinx Whites, regardless of race/ethnicity. [ABSTRACT FROM AUTHOR]

Purpose: To examine self-reported (30-day) sleep versus nightly actigraphy-assessed sleep concordance in long-term survivors of childhood cancer. Methods: Four hundred seventy-seven participants enrolled in the St. Jude Lifetime Cohort (53.5% female, median (range) age 34.3 (19.3–61.6) years, 25.4 (10.9–49.3) years from diagnosis) completed the Pittsburgh Sleep Quality Index and ≥ 3 nights of actigraphy. Participants had neurocognitive impairment and/or a self-reported prolonged sleep onset latency (SOL). Self-reported 30-day sleep and nightly actigraphic sleep measures for sleep duration, SOL, and sleep efficiency (SE) were converted into ordinal categories for calculation of weighted kappa coefficients. General linear models estimated associations between measurement concordance and late effects. Results: Agreements between self-reported and actigraphic measures were slight to fair for sleep duration and SOL measures (kw = 0.20 and kw = 0.22, respectively; p < 0.0001) and poor for SE measures (kw = 0.00, p = 0.79). In multivariable models, severe fatigue and poor sleep quality were significantly associated with greater absolute differences between self-reported and actigraphy-assessed sleep durations (B = 26.6 [p < 0.001] and B = 26.8 [p = 0.01], respectively). Survivors with (versus without) memory impairment had a 44-min higher absolute difference in sleep duration (B = 44.4, p < 0.001). Survivors with, versus without, depression and poor sleep quality had higher absolute discrepancies of SOL (B = 24.5 [p = 0.01] and B = 16.4 [p < 0.0001], respectively). Poor sleep quality was associated with a 12% higher absolute difference in SE (B = 12.32, p < 0.0001). Conclusions: Self-reported sleep and actigraphic sleep demonstrated discordance in our sample. Several prevalent late effects were statistically significantly associated with increased measurement discrepancy. Future studies should consider the impacts of late effects on sleep assessment in adult survivors of childhood cancer. [ABSTRACT FROM AUTHOR]

Background: Young adult cancer survivors are at risk for subsequent human papillomavirus (HPV)-related malignancies. High-risk sexual behavior increases risk for HPV acquisition; HPV vaccination protects against infection. We aimed to determine the prevalence of sexual behaviors, factors related to high-risk sexual behaviors, and the relationship between sexual behaviors and HPV vaccine non-initiation among survivors. Methods: Survivors at comprehensive cancer centers, aged 18–26 years and 1–5 years post-treatment, reported sexual behaviors and HPV vaccine initiation (i.e., ≥ 1 dose). Multivariable logistic regression was performed to calculate odds ratios (OR) and 95% confidence intervals (95%CI) for factors associated with high-risk sexual behaviors (age at first intercourse < 16 years, ≥ 3 lifetime sexual partners, or condom use ≤ 50% of the time) and to explore the relationship between sexual behaviors and vaccine non-initiation. Results: Of the 312 participants (48.1% female, median age at cancer diagnosis 17.2 years and at survey 20.9 years), sexual intercourse was reported by 63.1%. Of those reporting intercourse, 74.6% reported high-risk sexual behavior. Factors related to high-risk sexual behavior included currently dating/partnered (OR = 4.39, 95%CI 2.5–7.7, P < 0.001) and perceived susceptibility to HPV (OR = 1.76, 95%CI 1.3-2.5, P < 0.001). Most survivors (75.3%) reported HPV vaccine non-initiation; sexual behaviors were not associated with vaccine non-initiation (P = 0.4). Conclusions: Many survivors participate in high-risk sexual behaviors, yet HPV vaccine initiation rates are low. Factors related to high-risk sexual behaviors can inform interventions to reduce risk for HPV acquisition among survivors. Implications for Cancer Survivors: Cancer survivors participate in sexual behaviors that increase risk for HPV acquisition and would benefit from vaccination. [ABSTRACT FROM AUTHOR]

Purpose: The study aims were to determine the prevalence of balance impairments in adult survivors of pediatric central nervous system (CNS) tumors, and to identify predictors of and limitations associated with balance impairments. Methods: Participants were adult survivors (N = 329) of pediatric CNS tumors. Balance was considered impaired among those with composite scores < 70 on the sensory organization test. Potential predictors of impaired balance were evaluated with generalized linear regression. Multivariable logistic regression was used to evaluate associations between balance impairment and function. Results: Balance impairment was observed in 48% of survivors, and associated with infratentorial tumor location (OR = 4.0, 95% CI, 2.0–7.6), shunt placement (OR = 3.5, 95% CI, 1.8–6.7), increased body fat percentage (OR = 1.1, 95% CI, 1.0–1.1), hearing loss (OR = 11.1, 95% CI, 5.6–22.2), flexibility limitations (OR = 2.0, 95% CI, 1.0–3.9), peripheral neuropathy (OR = 2.4, 95% CI, 1.2–4.5), and cognitive deficits (OR = 2.2, 95% CI, 1.1–4.7). In adjusted models, impaired balance was associated with limitations in overall physical performance (OR = 3.6, 95% CI, 2.0–6.3), mobility (OR = 2.6, 95% CI, 1.5–4.4), diminished walking endurance (OR = 2.9, 95% CI, 1.7–5.0), and non-independent living (OR = 2.0, 95% CI, 1.0–4.3). Conclusions: Nearly half of adult survivors of pediatric CNS tumors have impaired balance, which is associated with mobility and physical performance limitations. Interventions to address the complex needs of this population should be prioritized. Implications for Cancer Survivors: Survivors with identified risk factors should be closely evaluated for presence of balance impairment. Interventions tailored to improve balance also can positively affect function and mobility in survivors. [ABSTRACT FROM AUTHOR]

Both panel-count data and panel-binary data are common data types in recurrent event studies. Because of inconsistent questionnaires or missing data during the follow-ups, mixed data types need to be addressed frequently. A recently proposed semiparametric approach uses a proportional means model to facilitate regression analyses of mixed panel-count and panel-binary data. This method can use all available information regardless of the record type and provide unbiased estimates. However, the large number of nuisance parameters in the nonparametric baseline hazard function makes the estimating procedure very complicated and time-consuming. We approximated the baseline hazard function to simplify the estimating procedure. Simulation studies showed that our method performed similarly to that of the previous semiparametric likelihood-based method, but with much faster speed. Approximating the baseline hazard not only reduced the computational burden but also made it possible to implement the estimating procedure in a standard software, such as SAS. [ABSTRACT FROM AUTHOR]

In long-term follow-up studies on recurrent events, the observation patterns may not be consistent over time. During some observation periods, subjects may be monitored continuously so that each event occurence time is known. While during the other observation periods, subjects may be monitored discretely so that only the number of events in each period is known. This results in mixed recurrent-event and panel-count data. In these data, there is dependence among within-subject events. Furthermore, if the data are collected from multiple centers, then there is another level of dependence among within-center subjects. Literature exists for clustered recurrent-event data, but not for clustered mixed recurrent-event and panel-count data. Ignoring the cluster effect may lead to less efficient analysis. In this paper, we present a marginal modeling approach to take into account the cluster effect and provide asymptotic distributions of the resulting regression parameters. Our simulation study demonstrates that this approach works well for practical situations. It was applied to a study comparing the hospitalization rates between childhood cancer survivors and healthy controls, with data collected from 26 medical institutions across North America during more than 20 years of follow-up. [ABSTRACT FROM AUTHOR]

Purpose: This cross-sectional study compared breastfeeding outcomes among childhood cancer survivors to those of women in the general population and evaluated whether breastfeeding is adversely affected by cancer treatment or endocrine-related late effects. Methods: A self-reported survey ascertained breastfeeding practices and incorporated items from the questionnaires used in the Infant Feeding Practices Study II (IFPS II) to allow comparison with the general population. Among 710 eligible survivors, 472 (66%) responded. The participants were predominantly non-Hispanic White (84%), married (73%), and had some college or less (60%). The mean maternal age at the time of birth of the first child after cancer treatment was 24 years (SD 24.3 ± 4.8). Results: Fewer survivors planned to breastfeed than did IFPS II controls (67% vs. 82%, P <.0001), and fewer survivors initiated breastfeeding (66% vs. 85%, P <.0001). The median breastfeeding duration was shorter among survivors, with early undesired weaning occurring sooner in the survivor group (1.4 months, interquartile range (IQR) 0.5–3.5 months) than in the IFPS II group (2.7 months, IQR 0.9–5.4 months). A higher proportion of survivors reported an unfavorable breastfeeding experience (19% vs. 7.5%, P <.0001) and early, undesired weaning (57.5%, 95% CI 51–64) than did IFPS II participants (45.2%, 95% CI 44–47, P =.0164). Among survivors who expressed intention and chose to breastfeed, 46% endorsed disrupted lactation related to physiologic problems with high risk in those overweight/obese. Conclusions: Survivors are at risk of negative breastfeeding experiences; however, lactation outcomes were not significantly associated with cancer diagnosis, treatments, or endocrine complications. Implications for cancer survivors: Prior research has not examined the association of cancer treatments and clinically validated late effects with lactation outcomes in a clinically diverse childhood cancer survivor cohort. Findings from this study suggest that childhood cancer survivors, especially those who are overweight/obese, are at risk of having negative breastfeeding experiences. Early undesired weaning, physiologic problems related to lactation and misconceptions about breastfeeding, especially fears of passing on cancer through breastmilk, highlight the need for counseling and specialized support to optimize lactation outcomes in this vulnerable population. [ABSTRACT FROM AUTHOR]

Cranial radiation therapy is associated with white matter-specific brain injury, cortical volume loss, mineralization, microangiopathy and neurocognitive impairment in survivors of childhood acute lymphoblastic leukemia. In this retrospective cross-sectional analysis, neurocognitive testing and 3 T brain MRI's were obtained in 101 survivors treated with cranial radiation. Small focal intracerebral hemorrhages only visible on exquisitely sensitive MRI sequences were identified and localized using susceptibility weighted imaging. Modified Poisson regression was used to assess the effect of cranial radiation on cumulative number and location of microbleeds in each brain region, and multiple linear regression was used to evaluate microbleeds on neurocognitive outcomes, adjusting for age at diagnosis and sex. At least one microbleed was present in 85% of survivors, occurring more frequently in frontal lobes. Radiation dose of 24 Gy conveyed a 5-fold greater risk (95% CI 2.57–10.32) of having multiple microbleeds compared to a dose of 18 Gy. No significant difference was found in neurocognitive scores with either the absence or presence of microbleeds or their location. Greater prevalence of microbleeds in our study compared to prior reports is likely related to longer time since treatment, better sensitivity of SWI for detection of microbleeds and the use of a 3 T MRI platform. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Survivors of childhood cancer require life-long outpatient healthcare, which may be impacted by health insurance. This study sought to understand survivors' utilization of outpatient healthcare provider services.Methods: The study examined cross-sectional survey data using an age-stratified sample from the Childhood Cancer Survivor Study of self-reported annual use of outpatient services. Multivariable logistic regression analyses were used to identify risk factors associated with utilization of services.Results: Six hundred ninety-eight survivors were surveyed, median age 36.3 years (range 22.2-62.6), median time from diagnosis 28.8 years (range 23.1-41.7). Almost all (93%) of survivors had at least one outpatient visit during the previous year; 81.3% of these visits were with a primary care providers (PCP), 54.5% were with specialty care physicians, 30.3% were with nurse practitioner/physician's assistants (NP/PA), and 14.2% were with survivorship clinic providers. Survivors with severe to life-threatening chronic health conditions had greater odds of utilizing a specialty care physician (OR = 5.15, 95% CI 2.89-9.17) or a survivorship clinic (OR = 2.93, 95% CI 1.18-7.26) than those with no chronic health conditions. Having health insurance increased the likelihood of seeking care from NP/PA (private, OR = 2.76, 95% CI 1.37-5.58; public, OR = 2.09, 95% CI 0.85-5.11), PCP (private, OR = 7.82, 95% CI 3.80-13.10; public, OR = 7.24, 95% CI 2.75-19.05), and specialty care (private, OR = 2.96, 95% CI 1.48-5.94; public, OR = 2.93, 95% CI 1.26-6.84) compared to without insurance.Conclusion: Most childhood cancer survivors received outpatient care from a PCP, but a minority received care from a survivorship clinic provider. Having health insurance increased the likelihood of outpatient care.Implications For Cancer Survivors: Targeted interventions in the primary care setting may improve risk-based, survivor-focused care for this vulnerable population. [ABSTRACT FROM AUTHOR]

Purpose: To describe and compare the prevalence of mental health access, preference, and use among pediatric cancer survivors and their siblings. To identify factors associated with mental health access and use among survivors.Methods: Six hundred ninety-eight survivors in the Childhood Cancer Survivor Study (median age = 39.4; median years from diagnosis = 30.8) and 210 siblings (median age = 40.4) were surveyed. Outcomes included having mental health insurance coverage, delaying care due to cost, perceived value of mental health benefits, and visiting a mental health provider in the past year.Results: There were no differences in mental health access, preferences, and use between survivors and siblings (p > 0.05). Among respondents with a history of distress, most reported not having seen a mental health provider in the past year (80.9% survivors vs. 77.1% siblings; p = 0.60). Uninsured survivors were more likely to defer mental health services due to cost (24.6 vs. 8.4%; p < 0.001). In multivariable models, males (OR = 2.96) and survivors with public (OR = 6.61) or employer-sponsored insurance (ESI; OR = 14.37) were more likely to have mental health coverage.Conclusions: Most childhood cancer survivors value having mental healthcare benefits; however, coverage and use of mental health services remain suboptimal. The most vulnerable of survivors, specifically the uninsured and those with a history of distress, are at risk of experiencing challenges accessing mental health care.Implications For Cancer Survivors: Childhood cancer survivors are at risk for experiencing high levels of daily life stress that is compounded by treatment-related sequelae. Integrative, system-based approaches that incorporate financial programs with patient education about insurance benefits can help reduce some of the financial barriers survivors face. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to investigate workplace experiences and turnover intention (consideration of leaving or changing a job) and to examine factors associated with turnover intention among survivors.Methods: Adult survivors of childhood cancer with a history of employment (n = 289) completed measures of workplace experiences (n = 50, 18-29 years; n = 183, 30-44 years; n = 56; > 45 years of age at follow-up). Turnover intention was assessed using three items from the Job Satisfaction Scale. Responses were dichotomized as reflecting high vs. low turnover intention. Path analysis was used to estimate the influence of demographic characteristics, treatment exposures (cranial radiation therapy [CRT]), and workplace experiences on turnover intention.Results: Thirty percent of survivors reported high turnover intention (95% CL, 25 to 36%). Exposure to CRT (P = 0.003), older attained age (P < 0.001), experiencing formal workplace discrimination (P = 0.008), and having lower continuance (P < 0.001) or affective commitment (P < 0.001) were associated with high turnover intention among survivors. Informal discrimination, mediated through job satisfaction, also influenced survivors' reported intent to leave their jobs.Conclusions: One third of adult survivors of childhood cancer report turnover intention, which is related to their cancer treatment, but more temporally proximal, workplace discrimination. Additional research is needed to understand the consequences of turnover intention among survivors.Implications For Cancer Survivors: Survivors and their health care providers should be aware of legislative policies related to workplace discrimination (e.g., American with Disabilities Act) and related implications for job turnover. [ABSTRACT FROM AUTHOR]

Purpose: To compare importance ratings of patient-reported outcomes (PROs) items from the viewpoints of childhood cancer survivors, parents, and clinicians for further developing short-forms to use in survivorship care.Methods: 101 cancer survivors, 101 their parents, and 36 clinicians were recruited from St. Jude Children's Research Hospital. Participants were asked to select eight items that they deemed useful for clinical decision making from each of the four Patient-Reported Outcomes Measurement Information System Pediatric item banks. These item banks were pain interference (20 items), fatigue (23 items), psychological stress (19 items), and positive affect (37 items).Results: Compared to survivors, clinicians rated more items across four domains that were statistically different than did parents (23 vs. 13 items). Clinicians rated five items in pain interference domain (ORs 2.33-6.01; p's < 0.05) and three items in fatigue domain (ORs 2.22-3.80; p's < .05) as more important but rated three items in psychological stress domain (ORs 0.14-0.42; p's < .05) and six items in positive affect domain (ORs 0.17-0.35; p's < .05) as less important than did survivors. In contrast, parents rated seven items in positive affect domain (ORs 0.25-0.47; p's < .05) as less important than did survivors.Conclusions: Survivors, parents, and clinicians viewed importance of PRO items for survivorship care differently. These perspectives should be used to assist the development of PROs tools. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to determine the evolution of neurocognitive problems from therapy completion to long-term follow-up in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only.Methods: We evaluated whether attention problems observed at therapy completion evolve into long-term executive dysfunction in 158 survivors treated on a single institution protocol. Treatment data (high-dose intravenous methotrexate exposure [serum concentration] and triple intrathecal chemotherapy injections) were collected. Parent report of behavior and direct cognitive testing of survivors was conducted at end of therapy, and survivors completed neurocognitive testing when > 5 years post-diagnosis.Results: At the end of chemotherapy, survivors (52% female; mean age 9.2 years) demonstrated higher frequency of impairment in sustained attention (38%) and parent-reported inattention (20%) compared to population expectations (10%). At long-term follow-up, survivors (mean age 13.7 years; 7.6 years post-diagnosis) demonstrated higher impairment in executive function (flexibility 24%, fluency 21%), sustained attention (15%), and processing speed (15%). Sustained attention improved from end of therapy to long-term follow-up (p < 0.001). Higher methotrexate AUC and greater number of intrathecal injections were associated with attention problems (p = 0.009, p = 0.002, respectively) at the end of chemotherapy and executive function (p < 0.001, p = 0.02, respectively) problems at long-term follow-up. Attention problems at the end of therapy were not associated with executive function problems at long-term follow-up (p's > 0.05). The direct effect of chemotherapy exposure predicted outcomes at both time points.Conclusions and Implications For Cancer Survivors: Survivors should be monitored for neurocognitive problems well into long-term survivorship, regardless of whether they show attention problems at the end of therapy. Treatment exposures are the best predictor of long-term complications. [ABSTRACT FROM AUTHOR]

Purpose: The majority of research examining posttraumatic stress symptoms/disorder (PTSS/PTSD) among adult survivors of childhood cancer has been oriented to cancer, assuming that cancer has been the most traumatic experience in their lives. Whether that assumption is valid, and how it might impact assessment of PTSS, is unknown.Methods: Survivors in the St. Jude Lifetime Cohort study completed an assessment of PTSS without cancer orientation, global psychological functioning, perceived stress, and cancer-related anxiety.Results: Participants (n = 2969; Mage = 32.5 ± 8.5 years, 24.1 years since diagnosis, 49.1% female) obtained a mean score on the PTSD Checklist of 27.7, which is comparable to a normative population. Using established cutoffs, 11.8% obtained scores in the at-risk range. Multivariable modeling indicated that psychological factors [global distress (p < 0.0001), perceived stress (p = 0.001), cancer-related anxiety (p < 0.0001)] and demographic variables [female gender (p < 0.0001), survivors with less than a college education (p = 0.002)] were risk factors for increased PTSS. Only 14.5% identified a cancer-related traumatic event, and there was no difference in PTSS scores between those who identified cancer vs. non-cancer events as most stressful (28.4 ± 12.6 vs. 28.5 ± 12.7, p = 0.93).Conclusion: One in eight adult long-term survivors of childhood cancer had PTSS above the cutoff, though subgroups (e.g., females and those with lower education) report more distress symptoms. Most adult survivors do not identify cancer as their most stressful event.Implications For Cancer Survivors: Screening for distress in survivorship clinics should not assume that distress is directly related to the survivor's cancer experience. [ABSTRACT FROM AUTHOR]

Purpose: Childhood cancer survivors are at risk for deficits in health-related quality of life (HRQL) as they age. Youth (8-12 years) and adolescent (13-20 years) versions of the Minneapolis-Manchester Quality of Life Instrument (MMQL) have been developed to address survivor-specific issues and are currently in use; the MMQL-Adult Form has now been developed to assess HRQL in childhood cancer survivors aged 21-55 years.Methods: The MMQL-Adult Form was administered to 499 adults: 65 cancer patients on-therapy, 107 off-therapy, and 327 healthy controls. Forty-four percent of patients were under 30 years old at cancer diagnosis. Principal components analysis was performed. We evaluated internal consistency reliability, stability (re-administration of the MMQL-Adult Form 2 weeks later), construct validity (concurrent administration of the SF-36), and known-groups validity (score comparisons across the three groups).Results: Principal components analysis resulted in retention of 44 items across six scales: social functioning, physical functioning, cognitive functioning, outlook on life, body image, and psychological functioning. Internal consistency (Cronbach's α) was 0.80-0.90 for individual scales and 0.95 overall. Strong intraclass correlations (0.98 overall) indicated high stability. The MMQL-Adult Form distinguished between known groups; healthy controls scored better than patients on four of six scales. The MMQL-Adult Form scales correlated highly with similar SF-36 scales, demonstrating construct validity.Conclusions: The MMQL-Adult Form is a reliable and valid self-report instrument for measuring multidimensional HRQL in cancer survivors. Development of this instrument ensures availability of a tool enabling cross-sectional and longitudinal assessment of HRQL in childhood cancer survivors as they age. [ABSTRACT FROM AUTHOR]

Background: The relationship between hormone exposure and breast cancer risk in women treated with chest radiotherapy for childhood cancer is uncertain.Methods: Participants included 1108 females from the Childhood Cancer Survivor Study who were diagnosed with childhood cancer 1970-1986, treated with chest radiotherapy, and survived to ages ⩾20 years. Hazard ratios (HRs) and 95% confidence intervals (CIs) from Cox models adjusted for chest radiation field, delivered dose, anthracycline exposure, and age at childhood cancer estimated risk.Results: Among 195 women diagnosed with breast cancer, 102 tumours were oestrogen-receptor positive (ER+). Breast cancer risk increased with ⩾10 years of ovarian function after chest radiotherapy vs <10 years (HR=2.89, CI 1.56-5.53) and for radiotherapy given within 1 year of menarche vs >1 year from menarche (HR=1.80, CI 1.19-2.72). Risk decreased with decreasing age at menopause (Ptrend=0.014). Risk factors did not differ for ER+ breast cancer. Survivors with an age at menopause <20 years treated with hormone therapy had a lower breast cancer risk than premenopausal survivors (HR=0.47, CI 0.23-0.94).Conclusions: Endogenous hormones are key contributors to breast cancer observed among childhood cancer survivors. Hormone therapy given for premature ovarian insufficiency does not fully replace the function that endogenous hormones have in breast cancer development. [ABSTRACT FROM AUTHOR]

Purpose: We compared health-related quality of life (HRQOL) between adult survivors of childhood cancer and siblings by investigating the mediating role of emotional distress on HRQOL assessment, and examining the extent to which emotional distress affected the item responses of HRQOL measures given the same underlying HRQOL (i.e., measurement non-invariance).Methods: Cancer survivors (7103) and siblings (390) enrolled in Childhood Cancer Survivor Study who completed the SF-36 measuring HRQOL and the Brief Symptom Inventory-18 measuring anxiety, depression, and somatization were analyzed. Multiple Indicators & Multiple Causes modeling was performed to identify measurement non-invariance related to emotional distress on the responses to HRQOL items. Mediation analysis was performed to test the effects of cancer experience on HRQOL accounting for the mediating role of emotional distress.Results: Twenty-nine percent, 40%, and 34% of the SF-36 items were identified with measurement non-invariance related to anxiety, depression, and somatization, respectively. Survivors reported poorer HRQOL than siblings in all domains (ps < 0.05), except for pain. Other than physical functioning and general health perceptions, poorer HRQOL was explained by the mediating role of emotional distress (ps < 0.05).Conclusions: Differences in HRQOL between survivors and siblings appear due, in part, to the mediating effect of emotional distress through which cancer experience influences the responses to HRQOL measures.Implications Of Cancer Survivors: Interventions to treat emotional distress may improve cancer survivors' HRQOL. [ABSTRACT FROM AUTHOR]

Purpose: Survivors of pediatric Hodgkin's lymphoma (HL) are at risk for a number of debilitating late effects. Excessive fatigue and poor sleep quality are primary complaints of HL survivors. Understanding the emotional and physical factors that influence fatigue and sleep quality may provide opportunities for intervention to improve health-related quality of life for HL survivors.Methods: Data from 751 adult survivors of childhood HL who participated in the Childhood Cancer Survivor Study (CCSS) from 2000-2002 were analyzed. Multivariable logistic regression analyses investigated the demographic, psychological, and physical variables that predicted clinically significant levels of poor sleep quality, fatigue, and excessive daytime sleepiness.Results: Survivors' self-reported level of emotional distress, pain, and physical functioning limitations did not differ from population norms. Clinically elevated levels of emotional distress (OR 8.38, 95% CI 4.28-16.42) and pain (OR 3.73, 95% CI 2.09-6.67) increased the risk for endorsing elevated levels of fatigue. Survivors with elevated levels of emotional distress (OR 6.83, 95% CI 2.71-15.90) and pain (OR 5.27, 95% CI 1.78-15.61) were more likely to report poor sleep quality. Pain (OR 2.11, 95% CI 1.39-3.34) was related to excessive daytime sleepiness.Conclusions: Emotional and physical factors are associated with elevated levels of fatigue, excessive daytime sleepiness, and poor sleep quality in survivors of pediatric HL. This is consistent with findings from research conducted with non-cancer survivors.Implications For Cancer Survivors: These results suggest that interventions designed to target sleep and fatigue difficulties in the general population may be well suited for pediatric HL survivors as well. [ABSTRACT FROM AUTHOR]

Purpose: Anthracyclines and chest irradiation place adult survivors of childhood cancer at risk of cardiomyopathy; many survivors do not obtain the recommended screening. Based on our recent clinical trial, the addition of telephone counseling to a printed survivorship care plan more than doubled survivors' risk-based screening. Here, we sought to measure the impact of specific factors targeted in the intervention for their impact on survivors' screening participation.Methods: Study population-survivors participating in a randomized longitudinal intervention trial. Survivor questionnaires and medical records at baseline and 1-year follow-up provided the data. Within- and between-group differences in factors were assessed at baseline and follow-up; structural equation modeling (SEM) identified direct and indirect effects on screening participation.Results: Of the 411 survivors, 55.3% were female, 89.3% white, 38.9% college graduates, and age 26-59 years (mean = 41 years, SD = 7.68 years). At follow-up, the counseling group demonstrated higher scores for intent to undergo screening (p < 0.001), adherence determination (p < 0.001), autonomous regulation (p < 0.001), competency (p = 0.03), perceived effort warranted for screening (p < 0.001), and perceived value of screening (p = 0.02). SEM identified four factors that directly influenced screening participation (n = 411, RMSEA = 0.02 [90% CI = 0.000-0.05]; CFI = 0.99; TLI = 0.99; WRMR = 0.63): the counseling intervention (p < 0.0001), intrinsic motivation (p < 0.0001), competency (p < 0.0001), and decisional control (p = 0.001); intrinsic motivation was also a mediator (p = 0.002) of screening participation.Conclusions: Direct interpersonal interaction that focused on multiple modifiable, autonomy-supportive factors powerfully enhances the efficacy of a print survivorship care plan in increasing survivors' screening participation. This finding challenges providers to reach beyond the disease treatment focus and embrace these strategies in their behavior change efforts. [ABSTRACT FROM AUTHOR]

Survival rates for most paediatric cancers have improved at a remarkable pace over the past four decades. In developed countries, cure is now the probable outcome for most children and adolescents who are diagnosed with cancer: their 5-year survival rate approaches 80%. However, the vast majority of these cancer survivors will have at least one chronic health condition by 40 years of age. The burden of responsibility to understand the long-term morbidity and mortality that is associated with currently successful treatments must be borne by many, including the research and health care communities, survivor advocacy groups, and governmental and policy-making entities. [ABSTRACT FROM AUTHOR]

Objective: Utilizing data from the largest study to date, we examined associations between maternal preconception/prenatal exposure to household chemicals and infant acute leukemia.Methods: We present data from a Children's Oncology Group case-control study of 443 infants (<1 year of age) diagnosed with acute leukemia [including acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML)] between 1996 and 2006 and 324 population controls. Mothers recalled household chemical use 1 month before and throughout pregnancy. We used unconditional logistic regression adjusted for birth year, maternal age, and race/ethnicity to calculate odds ratios (ORs) and 95% confidence intervals (CIs).Results: We did not find evidence for an association between infant leukemia and eight of nine chemical categories. However, exposure to petroleum products during pregnancy was associated with AML (OR = 2.54; 95% CI:1.40-4.62) and leukemia without mixed lineage leukemia (MLL) gene rearrangements ("MLL-") (OR = 2.69; 95% CI: 1.47-4.93). No associations were observed for exposure in the month before pregnancy.Conclusions: Gestational exposure to petroleum products was associated with infant leukemia, particularly AML, and MLL- cases. Benzene is implicated as a potential carcinogen within this exposure category, but a clear biological mechanism has yet to be elucidated. [ABSTRACT FROM AUTHOR]

Family history of testicular cancer is an established risk factor for adult testicular germ cell tumors (GCT). We evaluated the association between family history of cancer and pediatric GCT in a Children's Oncology Group case-control study that included 274 GCT cases (195 female and 79 male) diagnosed < age 15 years and 418 controls frequency matched to cases on sex and age. Family history data were collected through telephone interviews with biological mothers and fathers and unconditional logistic regression was used to evaluate associations with GCT adjusting for potential confounders. A family history of cancer with onset < age 40 years was associated with a reduced risk of GCT among female cases (Odds Ratio (OR) = 0.50, 95% Confidence Interval (CI) 0.28-0.89) and an increased risk among male cases (OR = 2.56, 95% CI 1.02-6.44). Male cases were more likely to report family history of melanoma compared with male controls (OR = 4.65, 95% CI 1.40-15.4). There was an inverse association between family history of ovarian or uterine cancers and GCT in girls (OR = 0.46, 95% CI 0.22-0.96). These sex and cancer site specific associations should be confirmed in additional studies as they may provide clues to the etiology of pediatric GCT. [ABSTRACT FROM AUTHOR]

Objective: We explored whether maternal medication use during pregnancy may be an important etiologic area for investigation in studies of infant leukemia.Methods: In this case-control study, associations were explored between specific medications as recorded in the medical records of 243 mothers of infants who were diagnosed with leukemia at < 18 months of age and 393 mothers ol infants without leukemia identified through random digit dialing. Cases included 157 acute lymphoblastic (ALL), 77 acute myeloid (AML), and nine other leukemias. A total of 27 different drugs that were prescribed for at least six women were analyzed.Results: Overall, non-statistically significant negative associations (Odds ratios, OR < 0.5) were observed with amoxicillin, nystatin, clomiphene, levothyroxine, cefaclor, and trimethobenzamide HCL. When cases were restricted to either myeloid or lymphoblastic leukemia, cotrimoxazole was prescribed for five ALL case mothers and no matched controls; no association with cotrimoxazole was observed with AML.Conclusions: Given the number of comparisons, chance cannot be ruled out for any of the associations found here. However, a strength of this study is the lack of recall bias. The disparate data observed between AML and ALL in some instances may indicate areas of interest; they will be explored further in a case-control study of infant leukemia that is currently underway. [ABSTRACT FROM AUTHOR]

Survivors of pediatric Hodgkin's lymphoma are at risk for radiation therapy-induced second malignant neoplasms (SMNs). We identified two variants at chromosome 6q21 associated with SMNs in survivors of Hodgkin's lymphoma treated with radiation therapy as children but not as adults. The variants comprise a risk locus associated with decreased basal expression of PRDM1 (encoding PR domain containing 1, with ZNF domain) and impaired induction of the PRDM1 protein after radiation exposure. These data suggest a new gene-exposure interaction that may implicate PRDM1 in the etiology of radiation therapy-induced SMNs. [ABSTRACT FROM AUTHOR]