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1.  Psychological Status in Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study 
Journal of Clinical Oncology  2009;27(14):2396-2404.
Psychological quality of life (QOL), health-related QOL (HRQOL), and life satisfaction outcomes and their associated risk factors are reviewed for the large cohort of survivors and siblings in the Childhood Cancer Survivor Study (CCSS). This review includes previously published manuscripts that used CCSS data focused on psychological outcome measures, including the Brief Symptom Inventory (BSI-18), the Medical Outcomes Survey Short Form-36 (SF-36), the Cantril Ladder of Life, and other self-report questionnaires. Comparisons and contrasts are made between siblings and survivors, and to normative data when available, in light of demographic/health information and abstracted data from the medical record. These studies demonstrate that a significant proportion of survivors report more symptoms of global distress and poorer physical, but not emotional, domains of HRQOL. Other than brain tumor survivors, most survivors report both good present and expected future life satisfaction. Risk factors for psychological distress and poor HRQOL are female sex, lower educational attainment, unmarried status, annual household income less than $20,000, unemployment, lack of health insurance, presence of a major medical condition, and treatment with cranial radiation and/or surgery. Cranial irradiation impacted neurocognitive outcomes, especially in brain tumor survivors. Psychological distress also predicted poor health behaviors, including smoking, alcohol use, fatigue, and altered sleep. Psychological distress and pain predicted use of complementary and alternative medicine. Overall, most survivors are psychologically healthy and report satisfaction with their lives. However, certain groups of childhood cancer survivors are at high risk for psychological distress, neurocognitive dysfunction, and poor HRQOL, especially in physical domains. These findings suggest targeting interventions for groups at highest risk for adverse outcomes and examining the positive growth that remains despite the trauma of childhood cancer.
doi:10.1200/JCO.2008.21.1433
PMCID: PMC2677925  PMID: 19255309
2.  Prevalence and Predictors of Risky and Heavy Alcohol Consumption Among Adult Siblings of Childhood Cancer Survivors 
Psycho-oncology  2012;22(5):1134-1143.
Objective
To describe alcohol consumption patterns and risk factors for heavy alcohol use among siblings of childhood cancer survivors compared to survivors and national controls.
Methods
Secondary analysis of prospectively collected data from two national surveys was performed including a cohort of 3,034 adult siblings of childhood cancer survivors (age 18-56 years) and 10,398 adult childhood cancer survivors both from the Childhood Cancer Survivor Study, plus 5,712 adult participants from the population-based National Alcohol Survey. Cancer-related experiences, self-reported current health and mental health were examined in relation to alcohol consumption patterns including heavy and risky drinking.
Results
Adult siblings of childhood cancer survivors were more likely to be heavy drinkers (ORadj=1.3; 1.0-1.6) and risky drinkers (ORadj=1.3; 1.1-1.6) compared to controls from a national sample. Siblings were also more likely to drink at these two levels compared to survivors. Factors associated with heavy drinking among siblings include being 18-21 years old (ORadj=2.9; 2.0-4.4), male (ORadj=2.3; 1.7-3.0), having a high school education or less (ORadj=2.4; 1.7-3.5), and drinking initiation at a young age (ORadj=5.1; 2.5-10.3). Symptoms of depression, (ORadj=2.1; 1.3-3.2), anxiety (ORadj=1.9; 1.1-3.3) and global psychiatric distress (ORadj=2.5; 1.5-4.3) were significantly associated with heavy alcohol use.
Conclusions
Siblings of children with cancer are more likely to be heavy drinkers as adults compared to childhood cancer survivors or national controls. Early initiation of drinking and symptoms of psychological distress should be identified during early adolescence and effective sibling-specific interventions should be developed and made available for siblings of children with cancer.
doi:10.1002/pon.3121
PMCID: PMC3648621  PMID: 22736595
alcohol; childhood cancer; heavy drinking; risky drinking; siblings; cancer; alcohol/drug use; mental health; psychological impact
3.  Neurocognitive Status in Long-Term Survivors of Childhood CNS Malignancies: A Report from the Childhood Cancer Survivor Study 
Neuropsychology  2009;23(6):705-717.
Background
Among survivors of childhood cancer, those with Central Nervous System (CNS) malignancies have been found to be at greatest risk for neuropsychological dysfunction in the first few years following diagnosis and treatment. This study follows survivors to adulthood to assess the long term impact of childhood CNS malignancy and its treatment on neurocognitive functioning.
Participants & Methods
As part of the Childhood Cancer Survivor Study (CCSS), 802 survivors of childhood CNS malignancy, 5937 survivors of non-CNS malignancy and 382 siblings without cancer completed a 25 item Neurocognitive Questionnaire (CCSS-NCQ) at least 16 years post cancer diagnosis assessing task efficiency, emotional regulation, organizational skills and memory. Neurocognitive functioning in survivors of CNS malignancy was compared to that of non-CNS malignancy survivors and a sibling cohort. Within the group of CNS malignancy survivors, multiple linear regression was used to assess the contribution of demographic, illness and treatment variables to reported neurocognitive functioning and the relationship of reported neurocognitive functioning to educational, employment and income status.
Results
Survivors of CNS malignancy reported significantly greater neurocognitive impairment on all factors assessed by the CCSS-NCQ than non-CNS cancer survivors or siblings (p<.01), with mean T scores of CNS malignancy survivors substantially more impaired that those of the sibling cohort (p<.001), with a large effect size for Task Efficiency (1.16) and a medium effect size for Memory (.68). Within the CNS malignancy group, medical complications, including hearing deficits, paralysis and cerebrovascular incidents resulted in a greater likelihood of reported deficits on all of the CCSS-NCQ factors, with generally small effect sizes (.22-.50). Total brain irradiation predicted greater impairment on Task Efficiency and Memory (Effect sizes: .65 and .63, respectively), as did partial brain irradiation, with smaller effect sizes (.49 and .43, respectively). Ventriculoperitoneal (VP) shunt placement was associated with small deficits on the same scales (Effect sizes: Task Efficiency .26, Memory .32). Female gender predicted a greater likelihood of impaired scores on 2 scales, with small effect sizes (Task Efficiency .38, Emotional Regulation .45), while diagnosis before age 2 years resulted in less likelihood of reported impairment on the Memory factor with a moderate effect size (.64). CNS malignancy survivors with more impaired CCSS-NCQ scores demonstrated significantly lower educational attainment (p<.01), less household income (p<.001) and less full time employment (p<.001).
Conclusions
Survivors of childhood CNS malignancy are at significant risk for impairment in neurocognitive functioning in adulthood, particularly if they have received cranial radiation, had a VP shunt placed, suffered a cerebrovascular incident or are left with hearing or motor impairments. Reported neurocognitive impairment adversely affected important adult outcomes, including education, employment, income and marital status.
doi:10.1037/a0016674
PMCID: PMC2796110  PMID: 19899829
Neurocognitive functioning; brain tumors; CNS malignancies; Childhood Cancer Survivor Study
4.  Scarring, Disfigurement, and Quality of Life in Long-Term Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study 
Journal of Clinical Oncology  2012;30(20):2466-2474.
Purpose
Childhood cancer survivors are at increased risk for adverse outcomes and chronic medical conditions. Treatment-related scarring, disfigurement, and persistent hair loss, in addition to their long-term impact on psychological distress or health-related quality of life (HRQOL), have received little attention.
Patients and Methods
Self-reported scarring/disfigurement and persistent hair loss were examined in 14,358 survivors and 4,023 siblings from the Childhood Cancer Survivor Study. Multivariable models were used to examine associations with demographic and cancer treatment. The impact of disfigurement and hair loss on HRQOL (ie, Medical Outcomes Short Form–36) and emotional distress (ie, Brief Symptom Inventory–18) was examined.
Results
Survivors reported a significantly higher rate of scarring/disfigurement compared with siblings for head/neck (25.1% v 8.4%), arms/legs (18.2% v 10.2%), and chest/abdomen (38.1% v 9.1%), as well as hair loss (14.0% v 6.3%). In age-, sex-, and race-adjusted models, cranial radiation exposure ≥ 36 Gy increased risk for head/neck disfigurement (relative risk [RR], 2.42; 95% CI, 2.22 to 2.65) and hair loss (RR, 4.24; 95% CI, 3.63 to 4.95). Adjusting for cranial radiation, age, sex, race, education, and marital status, survivor hair loss increased risk of anxiety (RR, 1.60; 95% CI, 1.23 to 2.07), whereas head/neck disfigurement increased risk of depression (RR, 1.19; 95% CI, 1.01 to 1.41). Limitations due to emotional symptoms were associated with head/neck disfigurement (RR, 1.24; 95% CI, 1.10 to 1.41), arm/leg disfigurement (RR, 1.19; 95% CI, 1.05 to 1.35), and hair loss (RR, 1.26; 95% CI, 1.09 to 1.47).
Conclusion
Survivors of childhood cancer are at increased risk for disfigurement and persistent hair loss, which is associated with future emotional distress and reduced quality of life. Future studies are needed to better identify and manage functional outcomes in these patients.
doi:10.1200/JCO.2011.39.3611
PMCID: PMC3397782  PMID: 22614987
5.  Prevalence and Predictors of Posttraumatic Stress Disorder in Adult Survivors of Childhood Cancer: a report from the Childhood Cancer Survivor Study 
Pediatrics  2010;125(5):e1124-e1134.
Objective
Recent studies have found that a subset of young adult survivors of childhood cancer report posttraumatic stress symptoms in response to their diagnosis and treatment. However, it is unclear if these symptoms are associated with impairment in daily functions and/or significant distress, thereby resulting in a clinical disorder. Furthermore, it is unknown whether this disorder continues into very long-term survivorship, including the 3rd and 4th decades of life. This study hypothesized that very long-term survivors of childhood cancer would be more likely to report symptoms of posttraumatic stress disorder, with functional impairment and/or clinical distress, compared to a group of healthy siblings.
Patients and Methods
6,542 childhood cancer survivors over the age of 18 who were diagnosed between 1970 and 1986 and 368 siblings of cancer survivors completed a comprehensive demographic and health survey.
Results
589 survivors (9%) and 8 siblings (2%) reported functional impairment and/or clinical distress in addition to the set of symptoms consistent with a full diagnosis of Posttraumatic Stress Disorder (PTSD). Survivors had more than a four-fold risk of PTSD compared to siblings (OR=4.14, 95%CI: 2.08-8.25). Controlling for demographic and treatment variables, increased risk of PTSD was associated with educational level of high school or less (OR=1.51, 95% CI=1.16-1.98), being unmarried (OR=1.99, 95% CI=1.58-2.50), annual income less than $20,000 (OR=1.63, 95% CI=1.21-2.20), and being unemployed (OR=2.01, 95% CI=1.62-2.51). Intensive treatment was also associated with increased risk of full PTSD (OR=1.36, 95% CI 1.06 -1.74).
Conclusions
Posttraumatic stress disorder is reported significantly more often by childhood cancer survivors than by sibling controls. Although most survivors are apparently doing well, a subset report significant impairment that may warrant targeted intervention.
doi:10.1542/peds.2009-2308
PMCID: PMC3098501  PMID: 20435702
childhood cancer; young adult
6.  Prevalence and Predictors of Prescription Psychoactive Medication Use in Adult Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study 
Purpose
Childhood cancer survivors are at-risk for late effects which may be managed pharmacologically. The purpose of this study was to estimate and compare the prevalence of psychoactive medication use of adult survivors of childhood cancer and sibling controls, identify predictors of medication use in survivors, and investigate associations between psychoactive medications and health-related quality of life (HRQOL).
Methods
Psychoactive medication use from 1994 to 2010 was evaluated in 10,378 adult survivors from the Childhood Cancer Survivor Study. A randomly selected subset of 3,206 siblings served as a comparison group. Multivariable logistic regression models were used to calculate odds ratios (OR) for baseline and new onset of self-reported psychoactive medication use and HRQOL.
Results
Survivors were significantly more likely to report baseline (22% vs. 15%, p<0.001) and new onset (31% vs. 25%, p<0.001) psychoactive medication use compared to siblings, as well as use of multiple medications (p<0.001). In multivariable models, controlling for pain and psychological distress, female survivors were significantly more likely to report baseline and new onset use of antidepressants (OR=2.66; 95% CI=2.01–3.52; OR=2.02; 95% CI=1.72–2.38, respectively) and multiple medications (OR=1.80; 95% CI=1.48–2.19; OR=1.77; 95% CI=1.48–2.13, respectively). Non-cranial radiation and amputation predicted incident use of analgesics >15 years following diagnosis. Antidepressants were associated with impairment across all domains of HRQOL, with the exception of physical function.
Conclusions
Prevalence of psychoactive medication use was higher among survivors for most medication classes, as was the use of multiple medications. Clinicians should be aware of the possible contribution of psychoactive medications to HRQOL.
doi:10.1007/s11764-012-0250-x
PMCID: PMC3568188  PMID: 23224753
psychoactive medication; quality of life; survivorship
7.  Antioxidant enzyme polymorphisms and neuropsychological outcomes in medulloblastoma survivors: a report from the Childhood Cancer Survivor Study 
Neuro-Oncology  2012;14(8):1018-1025.
Psychological or neurocognitive impairment is often seen in medulloblastoma survivors after craniospinal radiation; however, significant variability in outcomes exists. This study investigated the role of antioxidant enzyme polymorphisms in moderating this outcome and hypothesized that patients who had polymorphisms associated with lower antioxidant enzyme function would have a higher occurrence of impairment. From the Childhood Cancer Survivor Study (CCSS) cohort, 109 medulloblastoma survivors and 143 siblings were identified who completed the CCSS Neurocognitive Questionnaire (NCQ) and the Brief Symptom Inventory-18 (BSI-18) and who provided buccal DNA samples. Real-time polymerase chain reaction (PCR) allelic discrimination was used for SOD2 (rs4880), GPX1 (rs1050450), and GSTP1 (rs1695 and rs1138272) genotyping and PCR for GSTM1 and GSTT1 gene deletions. Outcomes on NCQ and BSI-18 subscale scores were examined in association with genotypes and clinical factors, including age at diagnosis, sex, and radiation dose, using univariate and multivariate analysis of variance. Patients <7 years of age at diagnosis displayed more problems with task efficiency (P < .001) and fewer problems with somatic complaints (P = .004) than did patients ≥7 years of age. Female patients reported more organization problems than did male patients (P = .02). Patients with homozygous GSTM1 gene deletion reported higher anxiety (mean null genotype = 47.3 ± 9.2, non-null = 43.9 ± 7.8; P = .04), more depression (null = 51.0 ± 9.8, non-null = 47.0 ± 9.4; P = .03), and more global distress (null = 50.2 ± 9.7, non-null = 45.2 ± 9.9; P = .01). All associations for the GSTM1 polymorphism remained statistically significant in a multivariate model controlling for age, sex, and radiation dose. Homozygous GSTM1 gene deletion was consistently associated with greater psychological distress in medulloblastoma survivors across multiple domains, suggesting that this genotype may predispose patients for increased emotional late effects.
doi:10.1093/neuonc/nos123
PMCID: PMC3408256  PMID: 22661588
Childhood Cancer Survivor Study; glutathione S-transferase polymorphisms; medulloblastoma; neuropsychological impairment; radiation therapy
8.  Fractures among long-term survivors of childhood cancer: A report from the Childhood Cancer Survivor Study 
Cancer  2012;118(23):5920-5928.
Background
Although reductions in bone mineral density are well-documented among children during treatment for cancer and among childhood cancer survivors, little is known about the long-term risk of fracture. The aim of this study was to ascertain the prevalence of and risk factors for fractures among individuals participating in the Childhood Cancer Survivor Study (CCSS).
Methods
Analyses included 7414 5+ year survivors of childhood cancer diagnosed between 1970-86 who completed the 2007 CCSS follow-up questionnaire and a comparison group of 2374 siblings. Generalized linear models stratified by sex were used to compare the prevalence of reported fractures between survivors and siblings.
Results
The median ages at follow-up among survivors and siblings were 36.2, (range: 21.2-58.8) and 38.1 years (range: 18.4-62.6), respectively with a median 22.7 years of follow-up after cancer diagnosis for survivors. Approximately 35% of survivors and 39% of siblings reported ≥1 fractures during their lifetime. The prevalence of fractures was lower among survivors than siblings, both in males (prevalence ratio=0.87, 95%CI=0.81-0.94, p<0.001) and females (prevalence ratio=0.94, 95%CI=0.86-1.04, p=0.22). In multivariable analyses, increasing age at follow-up, white race, methotrexate treatment and balance difficulties were associated with increased prevalence of fractures among female survivors (p=0.05). Among males, only smoking history and white race were associated with an increased prevalence of fracture (p<0.001).
Conclusions
Findings from this study indicate that the prevalence of fractures among adult survivors is not increased compared to that of siblings. Additional studies of bone health among aging female cancer survivors may be warranted.
doi:10.1002/cncr.27626
PMCID: PMC3439597  PMID: 22605509
9.  Diabetes Mellitus in Long-Term Survivors of Childhood Cancer: Increased Risk Associated with Radiation Therapy A Report for the Childhood Cancer Survivor Study (CCSS) 
Archives of internal medicine  2009;169(15):1381-1388.
Background
Childhood cancer survivors are at increased risk of morbidity and mortality. To further characterize this risk, this study aimed to compare the prevalence of diabetes mellitus (DM) in childhood cancer survivors and their siblings.
Methods
Participants included 8599 survivors in the Childhood Cancer Survivor Study (CCSS), a retrospectively ascertained North American cohort of long-term survivors who were diagnosed 1970–1986, and 2936 randomly selected siblings of CCSS survivors. The main outcome was self-reported DM.
Results
Survivors and siblings had mean ages of 31.5 years (range, 17.0–54.1) and 33.4 years (range, 9.6–58.4), respectively. DM was reported in 2.5% of survivors and 1.7% of siblings. Adjusting for body mass index (BMI), age, sex, race/ethnicity, household income, and insurance, survivors were 1.8 times more likely to report DM (95% confidence interval [CI], 1.3–2.5; P<0.001) than siblings, with survivors who received total body irradiation (odds ratio [OR], 12.6; 95% CI, 6.2–25.3; P<0.001), abdominal irradiation (OR, 3.4; 95% CI, 2.3–5.0; P<0.001) and cranial irradiation (OR, 1.6; 95% CI 1.0–2.3; P=0.03) at increased risk. In adjusted models, increased risk of DM was associated with: total body irradiation (OR 7.2; 95% CI, 3.4–15.0; P<0.001); abdominal irradiation (OR 2.7; 95% CI, 1.9–3.8; P<0.001); alkylating agents (OR 1.7; 95% CI, 1.2–2.3; P<0.01); and younger age at diagnosis (0–4 years; OR 2.4; 95% CI 1.3–4.6; P<0.01).
Conclusions
Childhood cancer survivors treated with total body or abdominal irradiation have an increased risk of diabetes that appears unrelated to BMI or physical inactivity.
doi:10.1001/archinternmed.2009.209
PMCID: PMC3529471  PMID: 19667301
Childhood cancer survivor; diabetes mellitus; abdominal radiation; total body irradiation
10.  Late-Occurring Neurologic Sequelae in Adult Survivors of Childhood Acute Lymphoblastic Leukemia: A Report From the Childhood Cancer Survivor Study 
Journal of Clinical Oncology  2009;28(2):324-331.
Purpose
Children with acute lymphoblastic leukemia (ALL) are often cured, but the therapies they receive may be neurotoxic. Little is known about the incidence and severity of late-occurring neurologic sequelae in ALL survivors. Data were analyzed to determine the incidence of adverse long-term neurologic outcomes and treatment-related risk factors.
Patients and Methods
We analyzed adverse neurologic outcomes that occurred after diagnosis in 4,151 adult survivors of childhood ALL who participated in the Childhood Cancer Survivor Study (CCSS), a retrospective cohort of 5-year survivors of childhood cancer diagnosed between 1970 and 1986. A randomly selected cohort of the survivors' siblings served as a comparison group. Self-reported auditory-vestibular-visual sensory deficits, focal neurologic dysfunction, seizures, and serious headaches were assessed.
Results
The median age at outcome assessment was 20.2 years for survivors. The median follow-up time to death or last survey since ALL diagnosis was 14.1 years. Of the survivors, 64.5% received cranial radiation and 94% received intrathecal chemotherapy. Compared with the sibling cohort, survivors were at elevated risk for late-onset auditory-vestibular-visual sensory deficits (rate ratio [RR], 1.8; 95% CI, 1.5 to 2.2), coordination problems (RR, 4.1; 95% CI, 3.1 to 5.3), motor problems (RR, 5.0; 95% CI, 3.8 to 6.7), seizures (RR, 4.6; 95% CI, 3.4 to 6.2), and headaches (RR, 1.6; 95% CI, 1.4 to 1.7). In multivariable analysis, relapse was the most influential factor that increased risk of late neurologic complications.
Conclusion
Children treated with regimens that include cranial radiation for ALL and those who suffer a relapse are at increased risk for late-onset neurologic sequelae.
doi:10.1200/JCO.2009.22.5060
PMCID: PMC2815720  PMID: 19917844
11.  POSTTRAUMATIC STRESS DISORDER (PTSD) IN SURVIVORS OF HODGKIN’S LYMPHOMA (HL): PREVALENCE OF PTSD AND PARTIAL-PTSD COMPARED TO SIBLING CONTROLS 
Psycho-oncology  2011;22(2):434-440.
Objectives
Studies of PTSD document a significant proportion of cancer survivors reporting severe posttraumatic stress (PTS) symptoms, even when they do not meet full diagnostic criteria. However, few studies have directly examined the clinical significance of these “partial-PTSD” symptoms in survivors. This study aimed to investigate the prevalence of PTSD symptoms in a cohort of long-term survivors of HL, and to explore the clinical relevance of the partial-PTSD phenomenon by assessing impairment of function secondary to sub-threshold symptomatology.
Methods
The Posttraumatic Diagnostic Scale (PDS), was completed by 105 HL survivors and 101 sibling controls. Survivors age at time of participation ranged from 24–71 years, age at time of diagnosis ranged from 6–61 years, and the median time since diagnosis was 16 years (range = 7 – 34).
Results
PTSD prevalence was not significantly higher in HL survivors (13%) compared to sibling controls (6.9%, p = .098). However, a significantly larger proportion of survivors (35.2%) met criteria for partial-PTSD compared to siblings (17.8%, p = .004). Moreover, the majority of the survivors with partial-PTSD (86.5%) reported experiencing some functional impairment related to these PTS symptoms.
Conclusions
A significant number of HL survivors experience PTS symptoms severe enough to result in functional impairment. These findings underscore the importance of future research detailing the psychological and functional outcomes in survivors with partial-PTSD, and of careful clinical practice that assesses for functional impairment secondary to partial-PTSD symptomatology, in male and female survivors, even years after completion of therapy.
doi:10.1002/pon.2109
PMCID: PMC3908687  PMID: 22162210
Hodgkin’s Lymphoma; Long-Term Survivors; Posttraumatic Stress; Survey; Cancer; Oncology
12.  Survivors of Childhood Cancer Have Increased Risk for Gastrointestinal Complications Later in Life 
Gastroenterology  2011;140(5):1464-1471.e1.
Background & Aims
Children who receive cancer therapy experience numerous acute gastrointestinal (GI) toxicities. However, the long-term GI consequences have not been extensively studied. We evaluated the incidence of adverse long-term GI outcomes and identified treatment-related risk factors.
Methods
Upper GI, hepatic, and lower GI adverse outcomes were assessed in cases randomly selected from participants in the Childhood Cancer Survivor Study, a study of 14,358 survivors of childhood cancer who were diagnosed between 1970 and 1986; data were compared with those from siblings. The median age at cancer diagnosis was 6.8 years (0–21.0 years), the median age at outcome assessment was 23.2 years (5.6–48.9 years) for survivors and 26.6 years (1.8–56.2 years) for siblings. Rates of self-reported, late complications of the GI tract (occurred 5 or more years after cancer diagnosis) were determined and associated with patient characteristics and cancer treatments, adjusting for age, sex, and race; data were compared with those from siblings.
Results
Compared with siblings, survivors had increased risk for late-onset complications of the upper GI tract (relative risk [RR]=1.8; 95% confidence interval [CI], 1.6–2.0), liver (RR=2.1; 95% CI, 1.8–2.5), and lower GI tract (RR=1.9; 1.7–2.2). The RR for requiring colostomy, ileostomy, or liver biopsy, or for developing liver cirrhosis were 5.6 (95% CI, 2.4–13.1), 24.1 (95% CI, 7.5–77.8), and 8.9 (95% CI, 2.0–40.0), respectively. Older age at diagnosis, intensified therapy, abdominal radiation, and abdominal surgery increased the risk of certain GI complications.
Conclusions
Individuals who received therapy for cancer during childhood have an increased risk of developing GI complications later in life.
doi:10.1053/j.gastro.2011.01.049
PMCID: PMC3081911  PMID: 21315721
tumor; chemotherapy; side effect; toxicity; pediatric
13.  ALCOHOL CONSUMPTION PATTERNS AND RISK FACTORS AMONG CHILDHOOD CANCER SURVIVORS COMPARED TO SIBLINGS AND GENERAL POPULATION PEERS 
Addiction (Abingdon, England)  2008;103(7):1139-1148.
Aims
This study describes alcohol consumption among adult survivors of pediatric cancer compared to sibling controls and a national sample of healthy peers. Risk factors for heavy drinking among survivors are described.
Design, Setting and Participants
Cross-sectional data were utilized from the Childhood Cancer Survivor Study including adult survivors of pediatric cancer (N=10,398), and a sibling cohort (n=3,034). Comparison data were drawn from the National Alcohol Survey (n=4,774).
Measurement
Alcohol consumption, demographic, cancer diagnosis, treatment and psychosocial factors were measured.
Findings
Compared to peers, survivors were slightly less likely to be risky (ORadj=0.9; CI 0.8-1.0) and heavy drinkers (ORadj=0.8; CI 0.7-0.9) and more likely to be current drinkers. Compared to siblings, survivors were less likely to be current, risky and heavy drinkers. Risk factors for survivors’ heavy drinking included being age 18-21 (ORadj=2.0; 95% CI 1.5-2.6), male (ORadj=2.1; 95% CI 1.8-2.6), having high school education or less (ORadj=3.4; 95% CI 2.7-4.4), and drinking initiation before age 14 (ORadj=6.9; 95% CI 4.4-10.8). Among survivors, symptoms of depression, anxiety, or somatization, activity limitations and anxiety about cancer were associated with heavy drinking. Cognitively compromising treatment, brain tumors and older age at diagnosis were protective.
Conclusions
Adult survivors of childhood cancer show only a modest reduction in alcohol consumption compared to peers despite their more vulnerable health status. Distress and poorer health are associated with survivor heavy drinking. Screening for alcohol consumption should be instituted in long-term follow-up care and interventions among survivors and siblings should be established to reduce risk for early drinking.
doi:10.1111/j.1360-0443.2008.02242.x
PMCID: PMC2791534  PMID: 18554347
childhood cancer survivor; alcohol consumption; late-effects; risky drinking; long-term follow-up care
14.  Pain in Long-Term Adult Survivors of Childhood Cancers and Their Siblings: A Report from the Childhood Cancer Survivor Study 
Pain  2011;152(11):2616-2624.
Little is known about pain among long-term adult survivors of childhood cancers. The study investigated pain prevalence in this population compared with sibling controls and examined pain-related risk factors. Three self-reported pain outcomes including pain conditions, prescription analgesics used, and pain attributed to cancer and treatment were assessed among 10,397 cancer survivors and 3,034 sibling controls from the Childhood Cancer Survivor Study (CCSS). Pain conditions (pain/abnormal sensation, migraines, and other headaches) were reported by 12.3%, 15.5%, and 20.5% of survivors respectively; 16.7% of survivors reported use of prescription analgesics, and 21% attributed pain to cancer and treatment. Risks of reporting pain conditions and using prescription analgesics were higher among survivors than siblings adjusting for sociodemographic factors. Younger age at diagnosis and a history of non-Hodgkin lymphoma, Wilms tumor, or neuroblastoma (compared to leukemia) were associated with greater risk of reporting pain conditions. A history of bone cancer or soft tissue sarcoma (compared to leukemia) was associated with greater risks of using prescription analgesics and cancer-related pain attribution. Non-brain directed scatter irradiation was associated with elevated risk for migraines and cancer-related pain attribution. Female gender and lower educational attainment were associated with increased reports of all three pain outcomes; minority status, unemployment, and being single were associated with greater risks for reporting pain conditions. These findings contribute to the understanding of pain and associated risk factors among adult survivors of childhood cancer and suggest areas of focus for pain intervention.
doi:10.1016/j.pain.2011.08.006
PMCID: PMC3304496  PMID: 21907493
Long-term adult survivors of childhood cancer; Self-reported pain; Pain attribution; Risk factors
15.  Suicide Ideation in Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study 
Journal of Clinical Oncology  2009;28(4):655-661.
Purpose
To evaluate risk of suicide ideation (SI) after childhood cancer, prevalence of SI in a cohort of adult survivors of pediatric cancers was compared with prevalence in a sibling comparison group. The relationship of SI to cancer treatment and current health was examined, and the hypothesis that poor physical health is significantly associated with suicidality, after adjusting for depression, was specifically tested.
Methods
Nine thousand one hundred twenty-six adult survivors of childhood cancer and 2,968 siblings enrolled onto the Childhood Cancer Survivor Study completed a survey describing their demographics and medical and psychological functioning, including SI in the prior week.
Results
Of survivors, 7.8% reported SI compared with 4.6% of controls (odds ratio = 1.79; 95% CI, 1.4 to 2.4). Suicidality was unrelated to age, age at diagnosis, sex, cancer therapy, recurrence, time since diagnosis, or second malignancy. SI was associated with primary CNS cancer diagnosis, depression, and poor health outcomes including chronic conditions, pain, and poor global health rating. A logistic regression analysis showed that poor current physical health was significantly associated with SI even after adjusting for cancer diagnosis and depression.
Conclusion
Adult survivors of childhood cancers are at increased risk for SI. Risk of SI is related to cancer diagnosis and post-treatment mental and physical health, even many years after completion of therapy. The association of suicidal symptoms with physical health problems is important because these may be treatable conditions for which survivors seek follow-up care and underscores the need for a multidisciplinary approach to survivor care.
doi:10.1200/JCO.2009.22.8635
PMCID: PMC2816000  PMID: 19841325
16.  Neurocognitive Functioning in Adult Survivors of Childhood Non-Central Nervous System Cancers 
Background
We sought to measure self-reported neurocognitive functioning among survivors of non-central nervous system (CNS) childhood cancers, overall and compared with a sibling cohort, and to identify factors associated with worse functioning.
Methods
In a retrospective cohort study, 5937 adult survivors of non-CNS cancers and 382 siblings completed a validated neuropsychological instrument with subscales in task efficiency, emotional regulation, organization, and memory. Scores were converted to T scores; scores in the worst 10% of siblings’ scores (ie, T score ≥63) were defined as impaired. Non-CNS cancer survivors and siblings were compared with multivariable linear regression and log-binomial regression. Among survivors, log-binomial models assessed the association of patient and treatment factors with neurocognitive dysfunction. All statistical tests were two-sided.
Results
Non-CNS cancer survivors had similar or slightly worse (<0.5 standard deviation) mean test scores for all four subscales than siblings. However, frequencies of impaired survivors were approximately 50% higher than siblings in task efficiency (13.0% of survivors vs 7.3% of siblings), memory (12.5% vs 7.6%), and emotional regulation (21.2% vs 14.4%). Impaired task efficiency was most often identified in patients with acute lymphoblastic leukemia who received cranial radiation therapy (18.1% with impairment), myeloid leukemia who received cranial radiation therapy (21.2%), and non-Hodgkin lymphoma (13.9%). In adjusted analysis, diagnosis age of younger than 6 years, female sex, cranial radiation therapy, and hearing impairment were associated with impairment.
Conclusion
A statistically and clinically significantly higher percentage of self-reported neurocognitive impairment was found among survivors of non-CNS cancers than among siblings.
doi:10.1093/jnci/djq156
PMCID: PMC2886093  PMID: 20458059
17.  Cancer Prevention and Screening Practices of Siblings of Childhood Cancer Survivors: A Report from the Childhood Cancer Survivor Study 
Objective
To compare the skin and breast/cervical cancer prevention/screening practices of adult siblings of childhood cancer survivors with controls and to identify modifying factors for these practices.
Methods
Cross-sectional, self-report data from 2,588 adult siblings of 5+ year survivors of childhood cancer were analyzed to assess cancer prevention/screening practices. Two age, sex and race/ethnicity-matched samples (n=5,915 and n=37,789) of the Behavioral Risk Factor Surveillance System participants served as the comparison populations. Sociodemographic and cancer-related data were explored as modifying factors for sibling cancer prevention/screening practices through multivariable logistic regression.
Results
Compared to controls, siblings were more likely to practice skin cancer prevention behaviors: use of protective clothing (OR 2.85, 95% 2.39-3.39), use of shade (OR 2. 11, 95% 1.88-2.36), use of sunscreen (OR 1.27, 95% 1.14-1.40), and wearing a hat (OR 1.77, 95% 1.58-1.98). No differences were noted for breast/cervical cancer screening including mammography and Pap testing. Having less than a high school education and lack of health insurance were associated with diminished cancer prevention/screening behaviors. Survivor diagnosis, treatment intensity, adverse health, chronic health conditions, and second cancers were not associated with sibling cancer prevention/screening behaviors.
Conclusions
Siblings of cancer survivors report greater skin cancer prevention practices when compared with controls; however, no differences were noted for breast/cervical cancer screening practices. Access to care and lack of education may be associated with decreased cancer prevention/screening behaviors. Interventions are needed to address these barriers.
Impact
Research should be directed at understanding the impact of the cancer experience on sibling health behaviors.
doi:10.1158/1055-9965.EPI-11-1095
PMCID: PMC3392493  PMID: 22576363
Siblings; survivor; childhood cancer; prevention; screening
18.  Predictors of Marriage and Divorce in Adult Survivors of Childhood Cancers: A Report from the Childhood Cancer Survivor Study 
Background/Objective
Adult survivors of childhood cancer can have altered social functioning. We sought to identify factors that predict marriage and divorce outcomes in this growing population.
Methods
Retrospective cohort study of 8,928 ≥ five-year adult survivors of childhood malignancy and 2,879 random sibling controls participating in the Childhood Cancer Survivor Study. Marital status, current health, psychological status, and neurocognitive functioning were determined from surveys and validated instruments.
Results
Survivors were more likely to be never-married than siblings (relative risk (RR) = 1.21; 95% confidence interval (CI) 1.15–1.26) and the U.S. population (RR=1.25; 95% CI= 1.21 – 1.29), after adjusting for age, gender, and race. Patients with central nervous system (CNS) tumors were at greatest risk for not marrying (RR=1.50; 95% CI= 1.41–1.59). Married survivors divorced at frequencies similar to controls. In multivariable regression analysis, non-marriage was most associated with cranial radiation (RR=1.15; 95% CI=1.02–1.31 for >2400 centigray). In analysis of neurobehavioral functioning, non-marriage was associated with worse task efficiency (RR=1.27; 95% CI=1.20–1.35), but not with emotional distress, or problems with emotional regulation, memory, or organization. Physical conditions predictive of non-marriage included short stature (RR=1.27; 95% CI=1.20–1.34) and poor physical function (RR=1.08; 95% CI=1.00–1.18). Structural equation modeling suggested that cranial radiation influenced marriage status through short stature, cognitive problems, and poor physical function.
Conclusions
Childhood cancer survivors married at lower frequencies compared to peers. Patients with CNS tumors, cranial radiation, impaired processing efficiency, and short stature were more likely to never marry. Divorce patterns in survivors were similar to peers.
doi:10.1158/1055-9965.EPI-08-0959
PMCID: PMC2768276  PMID: 19815636
Survivorship; Cancer; Predictors; Marriage; Divorce
19.  Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort 
Objectives To assess the incidence of and risks for congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities among adult survivors of childhood and adolescent cancers.
Design Retrospective cohort study.
Setting 26 institutions that participated in the Childhood Cancer Survivor Study.
Participants 14 358 five year survivors of cancer diagnosed under the age of 21 with leukaemia, brain cancer, Hodgkin’s lymphoma, non-Hodgkin’s lymphoma, kidney cancer, neuroblastoma, soft tissue sarcoma, or bone cancer between 1970 and 1986. Comparison group included 3899 siblings of cancer survivors.
Main outcome measures Participants or their parents (in participants aged less than 18 years) completed a questionnaire collecting information on demographic characteristics, height, weight, health habits, medical conditions, and surgical procedures occurring since diagnosis. The main outcome measures were the incidence of and risk factors for congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities in survivors of cancer compared with siblings.
Results Survivors of cancer were significantly more likely than siblings to report congestive heart failure (hazard ratio (HR) 5.9, 95% confidence interval 3.4 to 9.6; P<0.001), myocardial infarction (HR 5.0, 95% CI 2.3 to 10.4; P<0.001), pericardial disease (HR 6.3, 95% CI 3.3 to 11.9; P<0.001), or valvular abnormalities (HR 4.8, 95% CI 3.0 to 7.6; P<0.001). Exposure to 250 mg/m2 or more of anthracyclines increased the relative hazard of congestive heart failure, pericardial disease, and valvular abnormalities by two to five times compared with survivors who had not been exposed to anthracyclines. Cardiac radiation exposure of 1500 centigray or more increased the relative hazard of congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities by twofold to sixfold compared to non-irradiated survivors. The cumulative incidence of adverse cardiac outcomes in cancer survivors continued to increase up to 30 years after diagnosis.
Conclusion Survivors of childhood and adolescent cancer are at substantial risk for cardiovascular disease. Healthcare professionals must be aware of these risks when caring for this growing population.
doi:10.1136/bmj.b4606
PMCID: PMC3266843  PMID: 19996459
20.  Unemployment among Adult Survivors of Childhood Cancer: A report from the Childhood Cancer Survivors Study 
Medical care  2010;48(11):1015-1025.
Background
Adult childhood cancer survivors report high levels of unemployment although it is unknown whether this is due to health or employability limitations.
Objectives
We examined two employment outcomes from 2002–2005 in the Childhood Cancer Survivor Study (CCSS): 1. health-related unemployment and 2. unemployed but seeking work. We compared survivors to a nearest-age CCSS sibling cohort and examined demographic and treatment-related risk groups for each outcome.
Methods
We studied 6339 survivors and 2280 siblings aged ≥25 years excluding those unemployed by choice. Multivariable generalized linear models evaluated whether survivors were more likely to be unemployed than siblings and whether certain survivors were at a higher risk for unemployment.
Results
Survivors (10.4%) reported health-related unemployment more often than siblings (1.8%; Relative Risk [RR] 6.07, 95% Confidence Interval [CI] 4.32–8.53). Survivors (5.0%) were more likely to report being unemployed but seeking work than siblings (2.7%; RR 1.90, 95% CI 1.43–2.54). Health-related unemployment was more common in female survivors than males (Odds Ratio [OR] 1.73, 95% CI 1.43–2.08). Cranial radiotherapy doses ≥25 Gy were associated with higher odds of unemployment (health-related: OR 3.47, 95% CI 2.54–4.74; seeking work: OR 1.77, 95% CI 1.15–2.71). Unemployed survivors reported higher levels of poor physical functioning than employed survivors, and had lower education and income and were more likely to be publicly insured than unemployed siblings.
Conclusions
Childhood cancer survivors have higher levels of unemployment due to health or being between jobs. High-risk survivors may need vocational assistance.
doi:10.1097/MLR.0b013e3181eaf880
PMCID: PMC3428202  PMID: 20940653
21.  Twenty Years of Follow-Up of Survivors of Childhood Osteosarcoma: A Report from the Childhood Cancer Survivor Study (CCSS) 
Cancer  2010;117(3):625-634.
BACKGROUND
Osteosarcoma survivors have received significant chemotherapy and have undergone substantial surgeries. Their very long term outcomes (20 year) are reported here.
METHODS
We assessed the long-term outcomes of 733 five-year survivors of childhood osteosarcoma diagnosed from 1970-1986 to provide a comprehensive evaluation of medical and psychosocial outcomes for survivors enrolled on the Childhood Cancer Survivor Study (CCSS). Outcomes evaluated included overall survival, second malignant neoplasms (SMNs), recurrent osteosarcoma, chronic health conditions, health status(general and mental health and functional limitations), and psycho-social factors. Outcomes of osteosarcoma survivors were compared to general-population statistics, other CCSS survivors, and CCSS siblings.
RESULTS
Survivors had a mean follow-up of 21.6 years. The overall survival of children diagnosed with osteosarcoma who survived 5-years at 20 years from original diagnosis was 88.6% (95% CI: 86.6-90.5%). The cumulative incidence of SMNs at 25 years was 5.4% with a Standardized Incidence Ratio of 4.79 (95% CI: 3.54-6.33, p<0.01). Overall, 86.9% of osteosarcoma survivors experienced at least one chronic medical condition and over 50% experienced two or more conditions. Compared to survivors of other cancers, osteosarcoma survivors did not differ in their reported general health status (OR=0.9, 95% CI: 0.7-1.2), but were more likely to report an adverse health status in at least one domain (OR=1.9, 95% CI: 1.6-2.2) with activity limitations (29.1%) being the most common.
CONCLUSIONS
Childhood osteosarcoma survivors in this cohort did relatively well considering their extensive treatment; but are at risk to experience chronic medical conditions and adverse health status. Survivors warrant life-long follow-up.
doi:10.1002/cncr.25446
PMCID: PMC3025070  PMID: 20922787
Osteosarcoma; childhood cancer; survivorship; outcomes; bone sarcoma
22.  Cardiovascular Risk Factors in Adult Survivors of Pediatric Cancer – a report from the Childhood Cancer Survivor Study 
Background
Childhood cancer survivors are at higher risk of morbidity and mortality from cardiovascular (CV) disease compared with the general population.
Methods
8,599 survivors (52% male) and 2,936 siblings (46% male).from the Childhood Cancer Survivor Study (CCSS), a retrospectively ascertained – prospectively followed study of persons who survived 5 years after childhood cancer diagnosed from 1970–1986 were evaluated for BMI ≥30 kg/m2 based on self reported heights and weights and self-reported use of medications for hypertension, dyslipidemia, and impaired glucose metabolism. The presence of ≥3 of the above constituted Cardiovascular Risk Factor Cluster (CVRFC) a surrogate for Metabolic Syndrome
Results
Survivors were more likely than siblings to take medications for hypertension (OR 1.9 95% CI 1.6–2.2), dyslipidemia (OR 1.6 95% CI 1.3–2.0) or diabetes (OR 1.7 95% CI 1.2–2.3). Among these young adults (mean age 32 years for survivors and 33 years for siblings) survivors were not more likely than siblings to be obese or have CVRFC. In a multivariable logistic regression analysis, factors associated with having CVRFC included: older age at interview (≥ 40 vs. < 30 years of age [OR 8.2 95% CI 3.5–19.9]), exposure to total body irradiation (OR 5.5 95% CI 1.5–15.8) or radiation to the chest and abdomen (OR 2.3 95% CI 1.2–2.4), and physical inactivity (OR 1.7 95% CI 1.1–2.6).
Conclusions
Among adult survivors of pediatric cancer, older attained age, exposure to TBI or abdominal plus chest radiation, and a sedentary lifestyle are associated with CVRFC.
doi:10.1158/1055-9965.EPI-09-0555
PMCID: PMC2805162  PMID: 20056636
survivor; cardiovascular risk factors; metabolic syndrome
23.  Psychoactive Medication Use and Neurocognitive Function in Adult Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study 
Pediatric blood & cancer  2012;60(3):486-493.
Background
Adult survivors of childhood cancer are at risk for long-term morbidities, which may be managed pharmacologically. Psychoactive medication treatment has been associated with adverse effects on specific neurocognitive processes in non-cancer populations, yet these associations have not been examined in adult survivors of childhood cancer.
Procedure
Outcomes were evaluated in 7,080 adult survivors from the Childhood Cancer Survivor Study using a validated self-report Neurocognitive Questionnaire. Multivariable logistic regression models were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for neurocognitive impairment using demographic and treatment factors and survivors’ report of prescription medication use.
Results
Controlling for cranial radiation, pain, psychological distress, and stroke/seizure, use of antidepressant medications was associated with impaired task efficiency (OR=1.80, 95% CI=1.47–2.21), organization (OR=1.83, 95% CI=1.48–2.25), memory (OR=1.53, 95% CI=1.27–1.84) and emotional regulation (OR=2.06, 95% CI=1.70–2.51). Neuroleptics and stimulants were associated with impaired task efficiency (OR=2.46, 95% CI=1.29–4.69; OR=2.82, 95% CI=1.61–4.93, respectively) and memory (OR=2.08, 95% CI=1.13–3.82; OR=2.69, 95% CI=1.59–4.54, respectively). Anticonvulsants were associated with impaired task efficiency, memory and emotional regulation, although survivors who use these medications may be at risk for neurocognitive impairment on the basis of seizure disorder and/or underlying tumor location (CNS).
Conclusions
These findings suggest that specific psychoactive medications and/or mental health conditions may be associated with neurocognitive function in adult survivors of childhood cancer. The extent to which these associations are causal or indicative of underlying neurological impairment for which the medications are prescribed remains to be ascertained.
doi:10.1002/pbc.24255
PMCID: PMC3494805  PMID: 22848025
psychoactive medication; neurocognition; survivorship
24.  Radiation, Atherosclerotic Risk Factors and Stroke Risk in Survivors of Pediatric Cancer: a Report from the Childhood Cancer Survivor Study 
Background
The impact of childhood cranial radiation therapy (CRT) on stroke risk in adulthood, and the role of modifiable atherosclerotic risk factors, remains poorly defined. We assessed long-term incidence rates and stroke risk factors in survivors of childhood cancer followed by the Childhood Cancer Survivor Study (CCSS).
Patients and Methods
CCSS is a multi-institutional retrospective cohort study of 14,358 five-year survivors of childhood cancer and 4,023 randomly selected sibling controls with longitudinal follow up. Age-adjusted incidence rates of self-reported late-occurring (≥ 5 years after diagnosis) first-stroke were calculated. Multivariable Cox Proportional Hazards models were used to identify independent stroke predictors.
Results
During a mean follow-up of 23.3 years, 292 survivors reported a late-occurring stroke. The age-adjusted stroke rate per 100,000 person-years was 77 (95% Confidence Interval [CI] 62–96) compared to 9.3 (95% CI 4–23) for siblings. Treatment with CRT increased stroke risk in a dose dependent manner: hazard ratio (HR) 5.9 (95% CI 3.5–9.9) for 30–49 Gy CRT, and 11.0 (7.4–17.0) for 50+ Gy CRT. The cumulative stroke incidence in survivors treated with 50+ Gy CRT was 1.1% (95% CI 0.4–1.8) at 10 years post-diagnosis and 12% (95% CI 8.9–15.0) at 30 years. Hypertension (HTN) increased stroke hazard by 4-fold (95% CI 2.8–5.5) and in black survivors by 16-fold (95% CI 6.9–36.6).
Conclusion
Young adult pediatric cancer survivors have an increased stroke risk that is associated with CRT in a dose dependent manner. Atherosclerotic risk factors enhanced this risk and should be treated aggressively.
doi:10.1016/j.ijrobp.2013.03.034
PMCID: PMC3696633  PMID: 23680033
25.  Long-term psychosocial outcomes among bereaved siblings of children with cancer 
Context
The death of a child from cancer affects the entire family. Little is known about the long-term psychosocial outcomes of bereaved siblings.
Objectives
To describe: (1) the prevalence of risky health-behaviors, psychological distress, and social support among bereaved siblings; (2) potentially modifiable factors associated with poor outcomes.
Methods
Bereaved siblings were eligible for this dual-center, cross-sectional, survey-based study if they were ≥16 years-old and their parents had enrolled in one of three prior studies about caring for children with cancer at end of life. Linear regression models identified associations between personal perspectives before, during, and after the family's cancer experience and outcomes (health-behaviors, psychological distress, and social support).
Results
Fifty-eight siblings completed surveys (62% response rate). They were approximately 12 years bereaved, with a mean age of 26 years at the time of the survey (SD=7.8). Anxiety, depression, and illicit substance use increased during the year following their brother/sister's death, but then returned to baseline. Siblings who reported dissatisfaction with communication, poor preparation for death, missed opportunities to say “goodbye,” and/or a perceived negative impact of the cancer experience on relationships tended to have higher distress and lower social support scores (p<0.001-0.031). Almost all siblings reported their loss still affected them; half stated the experience impacted current educational and career goals.
Conclusion
How siblings experience the death of a child with cancer may impact their long-term psychosocial well-being. Sibling-directed communication and concurrent supportive care during the cancer experience and the year following sibling death may mitigate poor long-term outcomes.
doi:10.1016/j.jpainsymman.2014.05.006
PMCID: PMC4280260  PMID: 24880001
bereavement; siblings; pediatric cancer; psychological distress; resilience; psychosocial outcomes; survivorship

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