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.
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).
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.
Neurocognitive functioning; brain tumors; CNS malignancies; Childhood Cancer Survivor Study
Up to 40% of childhood cancer survivors may experience neurocognitive impairment in one or more specific domains. As such, regular monitoring has been recommended for patients exposed to cranial irradiation and/or antimetabolite chemotherapy. This study reports the results of a questionnaire developed to identify those survivors who may be experiencing neurocognitive problems.
Participants for this study were 7,121 members of the Childhood Cancer Survivor Study cohort (6,739 survivors and 382 siblings). These participants completed a new neurocognitive questionnaire designed to assess functions commonly affected by cancer therapy, as well as a standard measure of emotional functioning. A measure of cognitive and emotional functioning was also completed on a subset of the patients roughly seven years prior to the current questionnaire. Responses to the questionnaires among subgroups of survivors were then analyzed to examine the reliability and validity of the new neurocognitive questionnaire.
Four reliable factors were identified that assessed task efficiency, emotional regulation, organization, and memory skills. These neurocognitive factors accurately discriminated between survivors who were at “high risk” for neurocognitive dysfunction, due to neurologic abnormalities or a history of intensive focal cranial irradiation, from healthy “low risk” survivors and siblings.
The questionnaire demonstrated excellent reliability, as well as construct and discriminative validity. It appears to be a practical and efficient tool for monitoring neurocognitive outcomes in adult survivors of pediatric cancer.
Regular monitoring of neurocognitive functioning is recommended for pediatric cancer survivors exposed to cranial irradiation and/or antimetabolite chemotherapy. The Childhood Cancer Survivor Study - Neurocognitive Questionnaire appears to be a practical and efficient tool for such monitoring.
Childhood Cancer Survivor Study; neurocognitive; questionnaire; late effects
Childhood cancer survivors exposed to CNS irradiation are at increased risk for neurocognitive deficits; however, limited data exist linking outcomes with region-specific exposure to CNS irradiation. We report associations between region-specific radiation dose and self-reported neurocognitive and health-related quality of life (HRQOL) outcomes in 818 adult survivors of childhood central nervous system (CNS) malignancies from the Childhood Cancer Survivor Study. Survivors were compared with a sibling group and national normative samples to calculate standardized scores. Cumulative radiation dose was calculated for 4 specific brain regions. Logistic regression was used to estimate the association between radiation dose to specific brain regions and outcome measures of functional impairment adjusted for clinical and demographic factors, including sex and age at diagnosis. High radiation dose levels to temporal regions were associated with a higher risk for memory impairment (radiation doses ≥30 to <50 Gy: OR, 1.95; 95% CI, 1.01–3.78; dose ≥50 Gy: OR, 2.34; 95% CI, 1.25–4.39) compared with those with no radiation exposure. No such association was seen with radiation exposure to other regions. Exposure to temporal regions was associated with more social and general health problems, whereas exposure to frontal regions was associated with general health problems and physical performance limitations. Adult survivors of childhood CNS malignancies report higher rates of neuropsychological and HRQOL outcomes, which vary as a function of dose to specific neuroanatomical regions. Survivors with a history of radiation exposure to temporal brain regions are at increased risk for impairment in memory and social functioning.
CNS malignancies; Childhood Cancer Survivor Study (CCSS); health-related quality of life; neuropsychological functioning; radiation therapy
To determine risk factors associated with reduced adult height in survivors of childhood acute lymphoblastic leukemia (ALL).
Cross-sectional study. Attained adult height was determined among 2,434 ALL survivors participating in the Childhood Cancer Survivor Study, a cohort of five-year survivors of common pediatric cancers diagnosed from 1970–1986, and compared with 3,009 siblings.
All survivor treatment exposure groups (chemotherapy alone, chemotherapy with cranial or craniospinal radiotherapy) had decreased adult heights and an increased risk of adult short stature (height standard deviation score < −2) compared with siblings (p<0.001). Compared with siblings, the risk of short stature for survivors treated with chemotherapy alone was elevated (OR 3.4, 95% CI 1.9, 6.0). Among survivors, significant risk factors for short stature included diagnosis of ALL prior to puberty, higher dose cranial radiotherapy (≥20 Gy versus <20 Gy), any radiotherapy to the spine, and female sex.
Survivors of childhood ALL are at increased risk of adult short stature, including those treated with chemotherapy alone. Risk is highest for those treated with cranial and craniospinal radiotherapy at a young age.
chemotherapy; epidemiology; growth deficiency; late effects; radiation; survivorship
Adult survivors of childhood cancer and their siblings are compared on one of the most salient developmental milestones of adulthood, the ability to live independently.
Adult survivors of childhood cancers (n=6,047) and siblings (n=2,326), all 25 years of age and older, completed a long-term follow-up questionnaire that assessed adaptive, neurocognitive, and psychological functioning, as well as demographic and health status. Multivariable logistic regression analyses and structural equation modeling (SEM) were used to identify predictors of independent living.
Compared to siblings (n=206, 8.7%), survivors (n=1063; 17.7%) were more than twice as likely to live dependently (OR 2.07; 95% confidence interval [CI] 1.77–2.42). Survivors diagnosed with CNS tumors (OR 0.13, 95% CI 0.10–0.18) or leukemia (OR 0.29, 95% CI 0.23–0.27) were significantly less likely to live independently compared to those diagnosed with Hodgkin Lymphoma. Other risk factors for reduced independent living included cranial radiation (≤24Gy OR 0.76, 95% CI 0.62–0.93; >24Gy OR 0.31, 95% CI 0.24–0.41), use of neuroleptic, anticonvulsant, or psychostimulant medication (OR 0.32, 95% CI 0.24–0.43), attention and processing speed problems (OR 0.58, 95% CI 0.47–0.71), poor physical functioning (OR 0.49, 95% CI 0.38–0.63), depression (OR 0.68, 95% CI 0.53–0.88), and racial/ethnic minority status (OR 0.39, 95% CI 0.30–0.51). SEM demonstrated that neurocognitive functioning had both direct effects on independent living status, and indirect effects through use of neurologically-directed medication, depression, and poor mental health.
Adult survivors of childhood cancer who experience neurocognitive, psychological or physical late effects are less likely to live independently as adults.
Pediatric oncology; psychosocial; late effects; outcomes research
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.
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.
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.
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.
Survivorship; Cancer; Predictors; Marriage; Divorce
This study investigates physical performance limitations for sports and daily activities in recently diagnosed childhood cancer survivors and siblings.
The Swiss Childhood Cancer Survivor Study sent a questionnaire to all survivors (≥16 years) registered in the Swiss Childhood Cancer Registry, who survived >5 years and were diagnosed 1976–2003 aged <16 years. Siblings received similar questionnaires. We assessed two types of physical performance limitations: 1) limitations in sports; 2) limitations in daily activities (using SF-36 physical function score). We compared results between survivors diagnosed before and after 1990 and determined predictors for both types of limitations by multivariable logistic regression.
The sample included 1038 survivors and 534 siblings. Overall, 96 survivors (9.5%) and 7 siblings (1.1%) reported a limitation in sports (Odds ratio 5.5, 95%CI 2.9-10.4, p<0.001), mainly caused by musculoskeletal and neurological problems. Findings were even more pronounced for children diagnosed more recently (OR 4.8, CI 2.4–9.6 and 8.3, CI 3.7–18.8 for those diagnosed <1990 and ≥1990, respectively; p = 0.025). Mean physical function score for limitations in daily activities was 49.6 (CI 48.9–50.4) in survivors and 53.1 (CI 52.5–53.7) in siblings (p<0.001). Again, differences tended to be larger in children diagnosed more recently. Survivors of bone tumors, CNS tumors and retinoblastoma and children treated with radiotherapy were most strongly affected.
Survivors of childhood cancer, even those diagnosed recently and treated with modern protocols, remain at high risk for physical performance limitations. Treatment and follow-up care should include tailored interventions to mitigate these late effects in high-risk patients.
We examined whether survivors from the Childhood Cancer Survivor Study were less likely to be in higher skill occupations than a sibling comparison and whether certain survivors were at higher risk.
We created three mutually-exclusive occupational categories for participants aged ≥25 years: Managerial/Professional and Non-Physical and Physical Service/Blue Collar. We examined currently employed survivors (N=4845) and siblings (N=1727) in multivariable generalized linear models to evaluate the likelihood of being in the three occupational categories. Among all participants, we used multinomial logistic regression to examine the likelihood of these outcomes in comparison to being unemployed (survivors N=6671; siblings N=2129). Multivariable linear models were used to assess survivor occupational differences by cancer and treatment variables. Personal income was compared by occupation.
Employed survivors were less often in higher skilled Managerial/Professional occupations (Relative Risk=0.93, 95% Confidence Interval 0.89–0.98) than siblings. Survivors who were Black, were diagnosed at a younger age, or had high-dose cranial radiation were less likely to hold Professional occupations than other survivors. In multinomial models, female survivors’ likelihood of being in full-time Professional occupations (27%) was lower than male survivors (42%) and female (41%) and male (50%) siblings. Survivors’ personal income was lower than siblings within each of the three occupational categories in models adjusted for sociodemographic variables.
Adult childhood cancer survivors are employed in lower skill jobs than siblings. Survivors with certain treatment histories are at higher risk and may require vocational assistance throughout adulthood.
Neoplasms; Occupations; Survivors; Socioeconomic Factors; Late Effects; Female
Adult survivors of childhood central nervous system (CNS) malignancies are at high risk for long-term morbidity and late mortality. However, patterns of late mortality, the long-term risks of subsequent neoplasms and debilitating medical conditions, and sociodemographic outcomes have not been comprehensively characterized for individual diagnostic and treatment groups.
We collected information on treatment, mortality, chronic medical conditions, and neurocognitive functioning of adult 5-year survivors of CNS malignancies diagnosed between 1970 and 1986 within the Childhood Cancer Survivor Study. Using competing risk framework, we calculated cumulative mortality according to cause of death and cumulative incidence of subsequent neoplasms according to exposure and dose of cranial radiation therapy (RT). Neurocognitive impairment and socioeconomic outcomes were assessed with respect to dose of CNS radiotherapy to specific brain regions. Cumulative incidence of chronic medical conditions was compared between survivors and siblings using Cox regression models. All tests of statistical significance were two-sided.
Among all eligible 5-year survivors (n = 2821), cumulative late mortality at 30 years was 25.8% (95% confidence interval [CI] = 23.4% to 28.3%), due primarily to recurrence and/or progression of primary disease. Patients who received cranial RT of 50 Gy or more (n = 813) had a cumulative incidence of a subsequent neoplasm within the CNS of 7.1% (95% CI = 4.5% to 9.6%) at 25 years from diagnosis compared with 1.0% (95% CI = 0% to 2.3%) for patients who had no RT. Survivors had higher risk than siblings of developing new endocrine, neurological, or sensory complications 5 or more years after diagnosis. Neurocognitive impairment was high and proportional to radiation dose for specific tumor types. There was a dose-dependent association between RT to the frontal and/or temporal lobes and lower rates of employment, and marriage.
Survivors of childhood CNS malignancies are at high risk for late mortality and for developing subsequent neoplasms and chronic medical conditions. Care providers should be informed of these risks so they can provide risk-directed care and develop screening guidelines.
Positive health-related behaviors are essential for the future wellbeing of childhood cancer survivors, though relatively few maintain healthy behaviors into adulthood.
Neurocognitive function and emotional distress were examined in 6,440 adult survivors from the Childhood Cancer Survivor Study, and used to predict rates of expected health-related behaviors. Covariates included cancer diagnosis, age, sex, body mass index, insurance status, income, and antidepressant medication use, and multivariable models were constructed adjusting for these factors.
In multivariable regression models, survivors with neurocognitive problems in task efficiency (RR=0.77, 95% CI=0.72–0.84) were less likely to meet the Centers for Disease Control guidelines for weekly physical activity. Survivors with neurocognitive impairment were more likely to engage in general survivor care (RR=1.20, 95% CI=1.10–1.30), and less likely to engage in dental care (RR=0.92, 95% CI=0.88–0.97). Obese survivors were less likely to report receiving a bone density exam (RR=0.67, 95% CI=0.54–0.82), a mammogram (RR=0.71, 95% CI=0.57–0.89), and a skin exam (RR=0.78, 95% CI = 0.68–0.89). Survivors reporting somatization, i.e. vague physical symptoms associated with anxiety, were more likely to report receiving echocardiograms (RR=1.53, 95% CI = 1.32–1.77).
These results support the link between neurocognitive and emotional problems and health-related behaviors in adult survivors of childhood cancer. Monitoring neurocognitive and emotional outcomes may help to identify survivors at risk for poor adherence to prescribed health behaviors and health screening exams.
This study examined the longitudinal association between adolescent psychological problems following cancer treatment and obesity, limited exercise, smoking, and excess sun exposure during adulthood in the Childhood Cancer Survivor Study cohort.
Participants included 1,652 adolescent survivors of childhood cancer and 406 siblings of cancer survivors, initially evaluated at 12-17 years of age and ≥ 5 years post-diagnosis. A follow-up survey of these participants was conducted roughly 7 years later and included assessment of health status and health behaviors. Logistic regression models were used to assess the association between adolescent psychological problems and adult health behavior outcomes.
During adolescence, survivors demonstrated higher rates of attention deficits, emotional problems, externalizing behavior and social withdrawal compared to sibling controls. Social withdrawal was associated with adult obesity (OR = 1.5, 95% CI = 1.1 - 2.1) and physical inactivity (OR = 1.7, 1.1 - 2.5). Use of stimulant medication during adolescence was also associated with adult obesity (OR = 1.9, 1.1 – 3.2), while antidepressant use was associated with physical inactivity (OR = 3.2, 1.2 – 8.2).
Adolescent survivors of childhood cancer display higher rates of psychological problems compared to siblings of cancer survivors. These psychological problems are associated with an increased risk for obesity and poor heath behavior in adulthood, which may increase future risk for chronic health conditions and secondary neoplasms.
In order to decrease risk of future health problems, adolescent survivors of childhood cancer should be routinely screened and treated for psychological problems following cancer therapy.
Adolescence; Cancer; Psychological problems; Obesity; Oncology; Childhood Cancer Survivor Study
Long-term survivors of childhood cancer are at risk for fatigue, sleep problems, and neurocognitive impairment, though the association between these outcomes has not been previously examined.
Outcomes were evaluated in 1426 survivors from the Childhood Cancer Survivor Study using a validated Neurocognitive Questionnaire. Relative risks for neurocognitive impairment were calculated using demographic and treatment factors, and survivors’ report on the FACIT-Fatigue, the Short Form-36 Vitality Scale (SF-36-V), the Pittsburgh Sleep Quality Index (PSQI), and the Epworth Sleepiness Scale (ESS).
Neurocognitive impairment was identified in over 20% of survivors, using sibling-based norms for comparison. Multivariable logistic regression models revealed that fatigue (RR=1.34, 1.13–1.59), daytime sleepiness (RR=1.68, 1.55–1.83), poor sleep quality (RR=1.23, 1.01–1.49) and decreased vitality (RR=1.75, 95% CI 1.33–2.30) were all associated with impaired task efficiency. Likewise, fatigue (RR=1.77, 1.23–2.55), sleepiness (RR=1.38, 1.14–1.67) and decreased vitality (RR=3.08, 1.98–4.79) were predictive of emotional regulation problems. Diminished organization was associated with increased sleepiness (RR=1.80, 1.31–2.48) and decreased vitality (RR=1.90, 1.37–2.63). Impaired memory was associated with poor sleep quality (RR=1.45, 1.19–1.76), increased sleepiness (RR=2.05, 1.63–2.58), and decreased vitality (RR=2.01, 1.42–2.86). The impact of fatigue, sleepiness, sleep quality and vitality on neurocognitive outcomes was independent of the effects of cranial radiation therapy, steroids and antimetabolite chemotherapy, sex, and current age.
Neurocognitive function in long-term survivors of childhood cancer appears particularly vulnerable to the effects of fatigue and sleep disruption. These findings suggest sleep hygiene should be emphasized among survivors, as it may provide an additional mechanism for intervention to improve neurocognitive outcomes.
Childhood Cancer Survivor Study; CCSS; neurocognitive; sleep; fatigue; vitality
To identify risk factors for adverse psychological outcomes among adult siblings of long-term survivors of childhood cancer.
Cross-sectional, self-report data from 3,083 adult siblings (mean age 29 years, range 18-56 years) of 5+ year survivors of childhood cancer were analyzed to assess psychological outcomes as measured by the Brief Symptom Inventory-18 (BSI-18). Sociodemographic and health data, reported by both the siblings and their matched cancer survivors were explored as risk factors for adverse sibling psychological outcomes through multivariable logistic regression.
Self-reported symptoms of psychological distress, as measured by the global severity index of the BSI-18, were reported by 3.8% of the sibling sample. Less than 1.5% of siblings reported elevated scores on two or more of the subscales of the BSI-18. Risk factors for sibling depression included having a survivor brother (OR 2.22, 95% CI 1.42-3.55), and having a survivor with impaired general health (OR 2.15, 95% CI 1.18-3.78). Siblings who were younger than the survivor reported increased global psychological distress (OR 1.81, 95% CI 1.05-3.12), as did siblings of survivors reporting global psychological distress (OR 2.32, 95% CI 1.08-4.59). Siblings of sarcoma survivors reported more somatization than did siblings of leukemia survivors (OR 2.07, 95% CI 1.05-3.98).
These findings suggest that siblings of long-term childhood cancer survivors are psychologically healthy in general. There are, however, small subgroups of siblings at risk for long-term psychological impairment who may benefit from preventive risk-reduction strategies during childhood while their sibling with cancer is undergoing treatment.
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
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.
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).
Alcohol consumption, demographic, cancer diagnosis, treatment and psychosocial factors were measured.
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.
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.
childhood cancer survivor; alcohol consumption; late-effects; risky drinking; long-term follow-up care
Adult childhood cancer survivors report high levels of unemployment although it is unknown whether this is due to health or employability limitations.
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.
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.
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.
Childhood cancer survivors have higher levels of unemployment due to health or being between jobs. High-risk survivors may need vocational assistance.
The use of rehabilitation services to address musculoskeletal, neurological and cardiovascular late effects among childhood cancer survivors could improve physical function and health-related quality-of-life (HRQL). We describe physical therapy (PT) and chiropractic utilization among childhood cancer survivors and their association with HRQL.
The sample included 5+ year survivors from the Childhood Cancer Survivor Study (N=9,289). Questions addressing use of PT or chiropractic services and HRQL (Medical Outcomes Survey Short Form (SF-36)) were evaluated. Multivariable regression models compared PT and/or chiropractic utilization between survivors and siblings, and by diagnosis, treatment and demographic characteristics; associations between chronic disease, PT/chiropractic use, and HRQL were similarly evaluated.
Survivors were not more likely to use PT (OR 1.0; 95% CI 0.8-1.2) or chiropractic (OR 0.8; 95% CI 0.7-1.0) services than siblings. More survivors reported using chiropractic (12.4%) than PT (9.2%) services. Older age and having health insurance were associated with utilization of either PT or chiropractic services. Grade 3-4 chronic conditions and a CNS tumor or sarcoma history were associated with PT but not with chiropractic service utilization. Survivors with musculoskeletal (OR 1.8; 95% CI 1.1-2.9), neurological (OR 3.4; 95% CI 1.6-6.9), or cardiovascular (OR 3.3; 95% CI 1.6-6.9) chronic conditions who used PT/chiropractic services were more likely to report poor physical health than survivors who did not use services.
The reported prevalence of PT/chiropractic among survivors is consistent with that reported by siblings. Severity of late effects is associated with service use and with reporting poor physical health.
Implications for Cancer Survivors
Long-term childhood cancer survivors do not appear to utilize rehabilitation services to optimize physical function and support increased HRQL.
Physical therapy; chiropractic; childhood cancer survivor; health related quality of life
We examined the relationship of physical, mental, and neurocognitive function with employment and occupational status in the Childhood Cancer Survivor Study.
We included survivors ≥25 years of age with available Short Form-36 (physical and mental health component scores), Brief Symptom Inventory (depression, anxiety and somatization), and Neurocognitive Questionnaire (task efficiency, emotional regulation, organization, and memory). We generated relative risks (RR) from generalized linear models for these measures on unemployment (N=5386) and occupation (N=3763) outcomes adjusted for demographic and cancer-related factors, and generated sex-stratified models.
Poor physical health was associated with an almost 8-fold higher risk of health-related unemployment (p<0.001) compared to survivors with normal physical health. Male survivors with somatization and memory problems were approximately 50% (p<0.05 for both) more likely to report this outcome, while task efficiency limitations was significant for both sexes (males: RR=2.43, p<0.001; females: RR=2.28, p<0.001). Employed female survivors with task efficiency, emotional regulation, and memory limitations were 13%-20% (p<0.05 for all) less likely to work in professional or managerial occupations than unaffected females.
Physical problems may cause much of the health-related unemployment among childhood cancer survivors. While both male and female survivors with neurocognitive deficits – primarily in task efficiencies – are at risk for unemployment, employed female survivors with neurocognitive deficits may face poor occupational outcomes more often than males.
Childhood cancer survivors are at risk for poor employment outcomes. Screening and intervention for physical, mental and neurocognitive limitations could improve employment outcomes for this population.
pediatric cancer; employment status; physical health; mental health; neurocognitive function
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.
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.
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.
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.
Offspring of childhood cancer survivors may be at risk of genetic disease due to the mutagenic cancer treatments received by their parents. Congenital malformations were evaluated in a population-based cohort study of 1715 offspring of 3963 childhood cancer survivors and 6009 offspring of 5657 survivors’ siblings. The Danish Central Population Register, Cancer Registry and Hospital Register were used to identify study subjects and congenital malformations. Gonadal and uterine radiation doses were characterized based on standard radiation-treatment regimens. The prevalence of congenital malformations at birth in offspring of survivors (44 cases, 2.6%) was slightly higher but not statistically different from that of offspring of siblings (140 cases, 2.3%) [prevalence proportion ratio (PPR), 1.1; 95% confidence interval, 0.8– 1.5] or of the general population (observed-to-expected ratio, 1.2; 0.9– 1.6). Including malformations diagnosed later in life did not change the ratios appreciably. The risk for malformations was slightly higher in the offspring of irradiated parents than in that of non-irradiated parents (PPR 1.2 vs 1.0) but was unrelated to gonadal dose. This study provides evidence that cancer therapy of children does not increase the risk for malformations in their offspring. Continued monitoring of genetic risks among their offspring, however, is warranted.
cancer survivor; childhood cancer; germ-cell mutation; malformation; pregnancy outcome; radiation
The aim of this study was to evaluate the results of home-based exercise counselling with feedback from a pedometer on fatigue in adult survivors of childhood cancer.
Adult survivors of childhood cancer were recruited from the long-term follow-up clinic of the University Medical Centre Groningen, The Netherlands. A score of 70 mm on a visual analogue scale (scale, 0–100 mm) for fatigue was used as an inclusion criterion. Controls were recruited by the survivors among their healthy siblings or peers.
During 10 weeks, the counselor encouraged the survivors to change their lifestyle and enhance daily physical activity such as walking, cycling, housekeeping and gardening. As a feedback to their physical activity, the daily number of steps of each survivor was measured by a pedometer and registered using an online step diary at the start of the programme and after 4 and 10 weeks. Fatigue was the primary outcome measure, assessed with the Checklist Individual Strength (CIS) at start (T0), 10 weeks (T10) and 36 weeks (T36). Thirty-three healthy age-matched control persons were asked to complete the CIS.
Out of 486 cancer survivors, 453 were interested and were asked to complete the VAS to measure fatigue; 67 out of 254 respondents met the inclusion criteria, 21 refused, 46 were enrolled and eight dropped out during the study. The mean scores on the CIS in the survivors at T0 was 81.42 (SD ± 20.14) and at T10 62.62 (SD ± 20.68), which was a significant improvement (p < 0.0005). At T36, the end of the study, the mean CIS score was 63.67 (SD ± 23.12); this was a significant improvement compared with the mean CIS at the start (p < 0.0005). There was no significant difference in the mean CIS scores of the controls during the follow-up period.
The stimulation of daily physical activity using exercise counselling and a pedometer over 10 weeks leads to a significant decrease in fatigue in adult survivors of childhood cancer, and this improvement lasts for at least 36 weeks.
Fatigue; Childhood cancer survivors; Exercise counselling; Pedometer
Previous research from the Childhood Cancer Survivor Study (CCSS) has shown that risk of skin cancer is strongly associated with exposure to radiation therapy. The potential role of ultraviolet radiation exposure in survivors has not been described.
The CCSS is a retrospective cohort study designed to investigate late effects among 5-year survivors of children and adolescents diagnosed with cancer between 1970–1986. Data regarding current sun protection behavior were collected on 9,298 survivors and 2,950 sibling controls. Median age at follow-up was 31 years (range: 17–54).
In this cohort, childhood cancer survivors and siblings showed similar patterns of sunscreen use (67% vs. 66%). Survivors were significantly less likely to report having sunbathed in the previous year (none vs. any in previous year: RR=0.92, 95%CI=0.89–0.95) or use artificial tanning (none vs. any in previous year: RR=0.76, 95%CI=0.70–0.83). Compared to survivors without radiation therapy, survivors with radiation exposure showed increased use of sunscreen (RR=1.06, 95%CI=1.03–1.10), and less sunbathing (none vs. any in previous year; RR=0.89, 95%CI=0.86–0.92) or artificial tanning (none vs. any in previous year; RR=0.62, 95%CI=0.56–0.69). In adjusted multivariable analysis, statistically significant factors for regular sunscreen use in the past summer (vs. never/rarely) in the survivor population were being female, having lighter skin complexions, having previously been examined for skin cancer, and having skin that burned when in the sun unprotected.
Survivors of childhood cancer self-reported lower tanning practices than siblings. However, because of the potential increased risk of skin cancer from therapy-related exposures, future research should be directed at intervention studies to further reduce UV exposures.
Skin cancer; sun protection behaviors; survivor; radiation; siblings
Difficulties with negotiating and achieving desired social outcomes in life may be exacerbated by the experience of childhood cancer, including adverse effects from therapies used to achieve a cure. This review of previous publications from the Childhood Cancer Survivor Study (CCSS) and other relevant literature provides insight into the prevalence of, and risk factors for, poor educational attainment, less than optimal employment status, and interpersonal relationship issues among long-term survivors of childhood cancer. The impacts of emotional health and physical disability on social outcomes are also examined. Study results suggest that childhood cancer survivors generally have similar high school graduation rates, but are more likely to require special education services than sibling comparison groups. Survivors are slightly less likely than expected to attend college, and are more likely to be unemployed and not married as young adults. Cancers and treatments that result in impairment to the CNS, particularly brain tumors, or that impact sensory functioning, such as hearing loss, are associated with greater risk for undesirable social outcomes, as are emotional health problems and physical disability. This review of relevant data from CCSS and other studies provides information on risk factors for social problems into adulthood. A greater understanding of the long-term social impacts from the diagnosis and treatment of childhood cancer is critically important for developing targeted interventions to prevent or ameliorate adverse psychosocial effects.
This cross-sectional study collected baseline data on the health behaviours of a large population of survivors of childhood cancer in the UK, aged 18–30 years, compared with those of sex- and age-matched controls. Data from 178 young adult survivors of childhood cancer, diagnosed and treated at Bristol Children's Hospital, 184 peers from the survivors' GP practices and 67 siblings were collected by postal questionnaire. Conditional logistic regression analysis showed that, for matched sets of survivors and controls, survivors of a variety of childhood cancers reported lower levels of alcohol consumption (P=0.005), lower levels of cigarette smoking (P=0.027) and lower levels of recreational drug use (P=0.001) than controls. Analysis of matched sets of survivors and siblings showed similar trends but no significant differences. A health behaviour index for each participant was constructed from the data collected on five key health behaviours which influence future health status. Comparison of the means for each case group showed that survivors of childhood cancer were leading healthier lives than controls or siblings. This finding was expressed most clearly as the difference in the means of the health behaviour index for each case group, derived from five health behaviours (one-way ANOVA, P<0.001).
British Journal of Cancer (2002) 87, 1204–1209. doi:10.1038/sj.bjc.6600632 www.bjcancer.com
© 2002 Cancer Research UK
childhood cancer; health behaviour; young adults; cancer survivors
To determine the risk of thyroid dysfunction and subsequent thyroid cancer among childhood acute lymphoblastic leukemia (ALL) survivors.
Rates of self-reported thyroid dysfunction and thyroid cancer were determined among 3,579 ALL survivors participating in the Childhood Cancer Survivor Study, a cohort of 5-year survivors of pediatric cancers diagnosed from 1970–1986, and compared with 3,846 siblings and population rates, respectively.
The cumulative incidence of hypo- and hyperthyroidism among survivors 15 years following leukemia diagnosis was 1.6% (95% CI 1.1, 2.1) and 0.6% (95% CI 0.3, 1.1), respectively, both significantly increased compared with siblings. In multivariate analysis, survivors who received ≥20 Gy cranial radiotherapy plus any spinal radiotherapy had the highest risk of subsequent hypothyroidism (HR 8.3, 95% CI 3.3, 20.5) compared with those treated with chemotherapy alone. Craniospinal radiotherapy also was associated with an increased risk of subsequent hyperthyroidism (HR 6.1, 95% CI 1.1, 34.2) compared with chemotherapy alone, as well as an increased risk of subsequent thyroid cancers (SIR 30.3, 95% CI 14.5, 55.7) compared with population rates. In radiation dosimetry analysis, pituitary doses ≥20 Gy combined with thyroid doses ≥10 Gy were associated with hypothyroidism, whereas pituitary doses ≥20 Gy combined with thyroid doses ≥15 Gy were associated with hyperthyroidism.
The risk of thyroid dysfunction and thyroid cancer was increased among childhood ALL survivors treated with craniospinal radiotherapy. In these individuals, long-term surveillance is warranted as no obvious plateau in risk was seen, even after 25 years of follow-up.
late effects; leukemia; radiation; hypothyroidism; hyperthyroidism; thyroid cancer