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1.  Equivalence Ratio for Daunorubicin to Doxorubicin in Relation to Late Heart Failure in Survivors of Childhood Cancer 
Journal of Clinical Oncology  2015;33(32):3774-3780.
Purpose
Cumulative anthracycline dose is one of the strongest predictors of heart failure (HF) after cancer treatment. However, the differential risk for cardiotoxicity between daunorubicin and doxorubicin has not been rigorously evaluated among survivors of childhood cancer. These risks, which are based on hematologic toxicity, are currently assumed to be approximately equivalent.
Patients and Methods
Data from 15,815 survivors of childhood cancer who survived at least 5 years were used. Survivors were from the Emma Children's Hospital/Academic Medical Center (n = 1,349), the National Wilms Tumor Study (n = 364), the St Jude Lifetime Cohort Study (n = 1,695), and the Childhood Cancer Survivor Study (n = 12,407). The hazard ratio (HR) for clinical HF through age 40 years for doses of daunorubicin and doxorubicin (per 100-mg/m2 increments) was estimated by using Cox regression adjusted for sex, age at diagnosis, treatment with other anthracycline agents and chest radiation, and cohort membership.
Results
In total, 5,144 (32.5%) patients received doxorubicin as part of their cancer treatment, whereas 2,243 (14.7%) received daunorubicin. On the basis of 271 occurrences of HF during a median follow-up time after cohort entry of 17.3 years (range, 0.0 to 35.0 years), the cumulative incidence of HF at age 40 years was 3.2% (95% CI, 2.8% to 3.7%). The average ratio of HRs for daunorubicin to doxorubicin was 0.45 (95% CI, 0.23 to 0.73). A similar ratio was obtained by using a linear dose-response model, which yielded an HR of 0.49 (95% CI, 0.28 to 0.70).
Conclusion
Compared with doxorubicin, daunorubicin was less cardiotoxic among survivors of childhood cancer than most current guidelines suggest. This may have implications for follow-up guidelines. The feasibility of substitution of doxorubicin with daunorubicin in childhood cancer treatment protocols to reduce cardiotoxicity should be additionally investigated.
doi:10.1200/JCO.2015.61.5187
PMCID: PMC4737860  PMID: 26304888
2.  Recurrent stroke in childhood cancer survivors 
Neurology  2015;85(12):1056-1064.
Objective:
To estimate the rates and predictors of recurrent stroke among survivors of pediatric cancer who have had a first stroke.
Methods:
The Childhood Cancer Survivor Study is a retrospective cohort study with longitudinal follow-up that enrolled 14,358 survivors (<21 years old at diagnosis; diagnosed 1970–1986; survived ≥5 years after cancer diagnosis) and followed them prospectively since 1994. We surveyed 443 survivors who reported a first stroke to identify recurrent stroke, and estimated recurrent stroke rates ≥5 years after cancer diagnosis.
Results:
Among 329 respondents (74% response rate), 271 confirmed a first stroke at a median age of 19 years (range 0–53), and 70 reported a second stroke at a median age of 32 years (range 1–56). In a multivariable Cox proportional hazards model, independent predictors of recurrent stroke included cranial radiation therapy (CRT) dose of ≥50 Gy (vs none, hazard ratio [HR] 4.4; 95% confidence interval [CI] 1.4–13.7), hypertension (HR 1.9; 95% CI 1.0–3.5), and older age at first stroke (HR 6.4; 95% CI 1.8–23; for age ≥40 vs age 0–17 years). The 10-year cumulative incidence of late recurrent stroke was 21% (95% CI 16%–27%) overall, and 33% (95% CI 21%–44%) for those treated with ≥50 Gy of CRT.
Conclusion:
Survivors of childhood cancer, particularly those previously treated with high-dose cranial radiation, have a high risk of recurrent stroke for decades after a first stroke. Although these strokes are mostly occurring in young adulthood, hypertension, an established atherosclerotic risk factor, independently predicts recurrent stroke in this population.
doi:10.1212/WNL.0000000000001951
PMCID: PMC4603599  PMID: 26311747
3.  Predictors of Colorectal Cancer Surveillance among Radiation-treated Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study 
Cancer  2015;121(11):1856-1863.
Background
Childhood cancer survivors treated with radiotherapy to a field including the colon or rectum have an elevated risk of developing radiation-induced colorectal cancer (CRC). The Children's Oncology Group (COG) recommends colonoscopy every five years once reaching age 35 for at-risk survivors.
Methods
Analyses included 702 5-year survivors (CCSS) ≥36 years old who received ≥30 Gy abdominal, pelvic, or spine radiotherapy. Multivariable generalized linear models were used to calculate relative risks (RR) with 95% confidence intervals (95% CI) for adherence to the COG's CRC surveillance recommendations.
Results
With median age of 43 (range 36 to 58) years, 29.5% (207/702) met surveillance recommendations. In multivariable analyses, age ≥50 years vs. age 36-49 years (RR=2.6, 95% CI=2.0-3.4); reporting routine cancer follow-up visit within one year prior to study (RR=1.5, 95% CI=1.0-2.2); reporting ≥10 physician visits in the past year vs. 0-9 visits (RR=1.4, 95% CI=1.1-1.7); and discussing future cancer risk with a physician at their most recent follow-up visit (RR=1.4, 95% CI=1.1-1.7) were associated with adherence to CRC surveillance recommendations.
Conclusions
More than 70% of survivors at increased risk for CRC were not screened as recommended. Regular physician contact and discussion of screening was associated with a 60% increase in CRC surveillance.
Impact
Educational interventions targeted at survivors and their primary care physicians are needed to heighten knowledge of CRC risk following radiation and the importance of appropriate surveillance.
doi:10.1002/cncr.29265
PMCID: PMC4441567  PMID: 25649858
childhood cancer; survivor; colorectal; screening
4.  Survivors of Childhood Cancer in the United States: Prevalence and Burden of Morbidity 
Background
No studies have estimated the population-level burden of morbidity in individuals diagnosed with cancer as children (ages 0-19 years). We updated prevalence estimates of childhood cancer survivors as of 2011 and burden of morbidity in this population reflected by chronic conditions, neurocognitive dysfunction, compromised health-related quality of life and health status (general health, mental health, functional impairment, functional limitations, pain and fear/anxiety).
Methods
Surveillance Epidemiology and End Results Program data from 1975 to 2011 were used to update the prevalence of survivors of childhood cancers in the US. Childhood Cancer Survivor Study data were used to obtain estimates of morbidity burden indicators which were then extrapolated to SEER data to obtain population-level estimates.
Results
There were an estimated 388,501 survivors of childhood cancer in the US as of January 1, 2011, of whom 83.5% are ≥5 years post-diagnosis. The prevalence of any chronic condition among ≥5-year survivors ranged from 66% (ages 5-19) to 88% (ages 40-49). Estimates for specific morbidities ranged from 12% (pain) to 35% (neurocognitive dysfunction). Generally, morbidities increased by age. However, mental health and anxiety remained fairly stable and neurocognitive dysfunction exhibited initial decline and then remained stable by time since diagnosis.
Conclusions
The estimated prevalence of survivors of childhood cancer is increasing, as is the estimated prevalence of morbidity in those ≥5 years post-diagnosis.
Impact
Efforts to understand how to effectively decrease morbidity burden and incorporate effective care coordination and rehabilitation models to optimize longevity and well-being in this population should be a priority.
doi:10.1158/1055-9965.EPI-14-1418
PMCID: PMC4418452  PMID: 25834148
childhood cancer survivors; chronic conditions; neurocognitive functioning; health-related quality of life; health status
5.  Increasing Cardiomyopathy Screening in At-Risk Adult Survivors of Pediatric Malignancies: A Randomized Controlled Trial 
Journal of Clinical Oncology  2014;32(35):3974-3981.
Purpose
To determine whether the addition of advanced-practice nurse (APN) telephone counseling to a printed survivorship care plan (SCP) significantly increases the proportion of at-risk survivors who complete cardiomyopathy screening.
Patients and Methods
Survivors age ≥ 25 years participating in the Childhood Cancer Survivor Study who received cardiotoxic therapy and reported no history of cardiomyopathy screening in the previous 5 years were eligible for enrollment. The 472 participants (mean age, 40.1 years; range, 25.0 to 59.0; 53.3% women) were randomly assigned to either standard care, consisting of an SCP summarizing cancer treatment and cardiac health screening recommendations (n = 234), or standard care plus two APN telephone counseling sessions (n = 238). The primary outcome—completion of cardiomyopathy screening within 1 year—was validated by medical records and compared between the two arms using adjusted relative risks (RRs) with 95% CIs.
Results
Participants in the standard and APN counseling groups were not statistically different by demographic or clinical characteristics. At the time of 1-year follow-up, 107 (52.2%) of 205 survivors in the APN group completed screening compared with 46 (22.3%) of 206 survivors in the non-APN group (P < .001). With adjustment for sex, age (< 30 v ≥ 30 years), and Children's Oncology Group–recommended screening frequency group (annual, 2 years, or 5 years), survivors in the APN group were > 2× more likely than those in the control group to complete the recommended cardiomyopathy screening (RR, 2.31; 95% CI, 1.74 to 3.07).
Conclusion
The addition of telephone counseling to an SCP with cardiac health screening recommendations increases cardiomyopathy screening in at-risk survivors.
doi:10.1200/JCO.2014.57.3493
PMCID: PMC4251960  PMID: 25366684
6.  Decline in physical activity level in the Childhood Cancer Survivor Study cohort 
Background
We aimed to identify demographic and health-related predictors of declining physical activity levels over a four year period among participants in the Childhood Cancer Survivor Study.
Methods
Analyses included 7287 ≥5 year childhood cancer survivors and 2107 siblings who completed multiple follow-up questionnaires. Participants were classified as active if they met the Centers for Disease Control and Prevention guidelines for physical activity. Generalized linear models were used to compare participants whose physical activity levels declined from active to inactive over the study to those who remained active. Additionally, selected chronic conditions (CTCAE v4.03 Grade 3 and 4) were evaluated as risk factors in an analysis limited to survivors only.
Results
The median age at last follow-up among survivors and siblings was 36 (range: 21–58) and 38 (range: 21–62) years, respectively. The rate of decline did not accelerate over time among survivors when compared with siblings. Factors that predicted declining activity included BMI ≥30kg/m2 (RR=1.32, 95%CI=1.19–1.46, p<0.01), not completing high school (RR=1.31, 95%CI=1.08–1.60, p<0.01), and female sex (RR=1.33, 95%CI=1.22–1.44, p<0.01). Declining physical activity levels were associated with the presence of chronic musculoskeletal conditions (p=0.034), but not with the presence of cardiac (p=0.10), respiratory (p=0.92) or neurological conditions (p=0.21).
Conclusions
Interventions designed to maximize physical activity should target female, obese, and less educated survivors. Survivors with chronic musculoskeletal conditions should be monitored, counseled and/or referred for physical therapy.
Impact
Clinicians should be aware of low activity levels among sub-populations of childhood cancer survivors which may heighten their risk for chronic illness.
doi:10.1158/1055-9965.EPI-14-0213
PMCID: PMC4119523  PMID: 24842624
children; cancer; survivor; physical; activity
7.  Aging and Risk of Severe, Disabling, Life-Threatening, and Fatal Events in the Childhood Cancer Survivor Study 
Journal of Clinical Oncology  2014;32(12):1218-1227.
Purpose
The first generation of childhood cancer survivors is now aging into their fourth and fifth decades of life, yet health risks across the aging spectrum are not well established.
Methods
Analyses included 14,359 5-year survivors from the Childhood Cancer Survivor Study, who were first diagnosed when they were younger than 21 years old and who received follow-up for a median of 24.5 years after diagnosis (range, 5.0 to 39.3 years) along with 4,301 of their siblings. Among the survivors, 5,604 were at least 35 years old (range, 35 to 62 years) at last follow-up. Severe, disabling, life-threatening, and fatal health conditions more than 5 years from diagnosis were classified using the Common Terminology Criteria for Adverse Events, grades 3 to 5 (National Cancer Institute).
Results
The cumulative incidence of a severe, disabling, life-threatening, or fatal health condition was greater among survivors than siblings (53.6%; 95% CI, 51.5 to 55.6; v 19.8%; 95% CI, 17.0 to 22.7) by age 50 years. When comparing survivors with siblings, hazard ratios (HR) were significantly increased within the age group of 5 to 19 years (HR, 6.8; 95% CI, 5.5 to 8.3), age group of 20 to 34 years (HR, 3.8; 95% CI, 3.2 to 4.5), and the ≥ 35 years group (HR, 5.0; 95% CI, 4.1 to 6.1), with the HR significantly higher among those ≥ 35 years versus those 20 to 34 years old (P = .03). Among survivors who reached age 35 years without a previous grade 3 or 4 condition, 25.9% experienced a subsequent grade 3 to 5 condition within 10 years, compared with 6.0% of siblings (P < .001).
Conclusion
Elevated risk for morbidity and mortality among survivors increases further beyond the fourth decade of life, which affects the future clinical demands of this population relative to ongoing surveillance and interventions.
doi:10.1200/JCO.2013.51.1055
PMCID: PMC3986385  PMID: 24638000
8.  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
9.  Risk of Salivary Gland Cancer Following Childhood Cancer: A Report From The Childhood Cancer Survivor Study 
Purpose
To evaluate effects of radiotherapy, chemotherapy, cigarette smoking and alcohol consumption on the risk of second primary salivary gland cancer (SGC) in the Childhood Cancer Survivor Study (CCSS).
Methods
Standardized incidence ratios (SIR) and excess absolute risks (EAR) of SGC in the CCSS were calculated using incidence rates from Surveillance, Epidemiology and End Results population-based cancer registries. Radiation dose to the salivary glands was estimated based on medical records. Poisson regression was used to assess risks with respect to radiation dose, chemotherapy, smoking and alcohol consumption.
Results
During the time period of the study, 23 cases of SGC were diagnosed among 14,135 childhood cancer survivors. The mean age at diagnosis of the first primary cancer was 8.3 years, and the mean age at SGC diagnosis was 24.8 years. The incidence of SGC was 39-fold higher in the cohort than in the general population (SIR=39.4; 95% CI: 25.4–7.8). The EAR was 9.8 per 100,000 person years. Risk increased linearly with radiation dose (excess relative risk=0.36 per gray; 95% CI: 0.06 to 2.5) and remained elevated after 20 years. There was no significant trend of increasing risk with increasing dose of chemotherapeutic agents, pack-years of cigarette smoking or alcohol intake.
Conclusion
While the cumulative incidence of SGC was low, childhood cancer survivors treated with radiation experienced significantly increased risk for at least two decades following exposure, and risk was positively associated with radiation dose. Results underscore the importance of long-term follow up of childhood cancer survivors for the development of new malignancies.
doi:10.1016/j.ijrobp.2012.06.006
PMCID: PMC3500417  PMID: 22836059
10.  Radiation-Related Risk of Basal Cell Carcinoma: A Report From the Childhood Cancer Survivor Study 
Background
Basal cell carcinoma (BCC) is the most common malignancy in the United States. Ionizing radiation is an established risk factor in certain populations, including cancer survivors. We quantified the association between ionizing radiation dose and the risk of BCC in childhood cancer survivors.
Methods
Participants in the Childhood Cancer Survivor Study who reported a BCC (case subjects, n = 199) were matched on age and length of follow-up to three study participants who had not developed a BCC (control subjects, n = 597). The radiation-absorbed dose (in Gy) to the BCC location was calculated based on individual radiotherapy records using a custom-designed dosimetry program. Conditional logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations between demographic and treatment factors, therapeutic radiation dose, and surrogate markers of sun sensitivity (skin and hair color) and the risk of BCC. A linear dose–response model was fitted to evaluate the excess odds ratio per Gy of radiation dose.
Results
Among case subjects, 83% developed BCC between the ages of 20 and 39 years. Radiation therapy, either alone or in combination with chemotherapy, was associated with an increased risk of BCC compared with no chemotherapy or radiation. The odds ratio for subjects who received 35 Gy or more to the skin site vs no radiation therapy was 39.8 (95% CI = 8.6 to 185). Results were consistent with a linear dose–response relationship, with an excess odds ratio per Gy of 1.09 (95% CI = 0.49 to 2.64). No other treatment variables were statistically significantly associated with an increased risk of BCC.
Conclusions
Radiation doses to the skin of more than 1 Gy are associated with an increased risk of BCC.
doi:10.1093/jnci/djs298
PMCID: PMC3611815  PMID: 22835387
11.  Risk Factors for Smoking among Adolescent Survivors of Childhood Cancer: A Report from the Childhood Cancer Survivor Study 
Pediatric blood & cancer  2011;58(3):428-434.
Background
Few studies have examined risk factors for smoking among adolescent survivors of childhood cancer. The present study reports on the rate of smoking and identifies factors associated with smoking in a sample of adolescent survivors from the Childhood Cancer Survivor Study (CCSS).
Procedure
Participants included 307 adolescent survivors and 97 healthy siblings (ages 14-20) who completed a self-report survey of health, quality of life, and health behaviors.
Results
Smoking rates did not differ significantly between survivor and sibling groups (Ever Smokers: 28% vs. 33%, Recent Smokers: 10% vs. 9%, respectively). Ever smoking was significantly associated with peer smoking, smokers in the household, binging, suicidal behavior, and no history of CRT. There were significant interactions of peer smoking with gender and CRT for ever smoking and with binging for recent smoking. Recent smoking was more likely for survivors with other household smokers (RR=2.24, CI=1.21-4.16), past suicidality (RR=1.89, CI=1.00-3.56), and no CRT (RR=2.40, CI=1.12-5.17). Among survivors with few smoking friends, ever smoking was more likely for survivors with no CRT (RR=4.47, CI=1.43-13.9), and recent smoking was more likely among survivors who binged (RR=3.37, CI=1.17-9.71).
Conclusions
Despite the health risks associated with survivorship, nearly one in three adolescent survivors of childhood cancer has smoked. Exposure to other smokers, in particular, appears to increase the likelihood of smoking for some survivors. Providing smoking cessation programs targeted to family members, helping survivors choose nonsmoking friends, and teaching ways to resist smoking influences from peers may be important pathways for smoking prevention with adolescent survivors.
doi:10.1002/pbc.23139
PMCID: PMC3165077  PMID: 21618409
adolescents; childhood cancer; survivors; smoking
12.  Auditory Complications in Childhood Cancer Survivors: A Report from the Childhood Cancer Survivor Studya 
Pediatric blood & cancer  2011;57(1):126-134.
Background
Studies have found associations between cancer therapies and auditory complications, but data are limited on long-term outcomes and risks associated with multiple exposures.
Procedure
The Childhood Cancer Survivor Study is a retrospective cohort investigating health outcomes of long-term survivors (5+ years) diagnosed and treated between 1970 and 1986 compared to a randomly selected sibling cohort. Questionnaires were completed by 14,358 survivors of childhood cancer and 4,023 sibling controls. Analysis determined the first occurrence of four auditory conditions in two time periods: diagnosis to ≥ 5 years post diagnosis, and > 5 years post diagnosis. Multivariable analyses determined the relative risks (RR) and 95% confidence interval (CI) of auditory conditions by treatment exposure.
Results
Five or more years from cancer diagnosis, survivors were at increased risk of problems hearing sounds (RR=2.3; 95% CI: 1.8–2.8), tinnitus (RR=1.7; 95% CI: 1.4–2.1), hearing loss requiring an aid (RR=4.4; 95% CI: 2.8–6.9), and hearing loss in 1 or both ears not corrected by a hearing aid (RR=5.2; 95% CI: 2.8–9.5), when compared to siblings. Temporal lobe and posterior fossa radiation was associated with these outcomes in a dose-dependent fashion. Exposure to platinum compounds was associated with an increased risk of problems hearing sounds (RR=2.1; 95% CI: 1.3–3.2), tinnitus (RR=2.8; 95% CI: 1.9–4.2), and hearing loss requiring an aid (RR=4.1; 95% CI:2.5–6.7)
Conclusions
Childhood cancer survivors are at risk of developing auditory complications. Radiation and platinum compounds are determinants of this risk. Follow-up is needed to evaluate the impact of auditory conditions on quality of life.
doi:10.1002/pbc.23025
PMCID: PMC3091978  PMID: 21328523
late effects of therapy; radiation therapy
14.  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
15.  Attentional and executive dysfunction as predictors of smoking within the Childhood Cancer Survivor Study cohort 
Nicotine & Tobacco Research  2010;12(4):344-354.
Introduction:
Previous research has suggested that childhood cancer survivors initiate smoking at rates approaching those of healthy individuals, even though smoking presents unique risks to survivors. The present study explores whether the attentional and executive functioning (EF) deficits associated with cancer and treatment place survivors of childhood cancer at increased risk for smoking.
Methods:
Data from the Childhood Cancer Survivor Study were examined to identify concurrent and longitudinal correlates of tobacco use. We explored whether childhood attention problems and adulthood executive dysfunction were associated with smoking among adult survivors of childhood cancer.
Results:
Childhood attention problems emerged as a striking predictor of adult smoking nearly a decade later on average. Nearly half (40.4%) of survivors who experienced attention problems in childhood reported a history of smoking, a significantly higher rate of ever smoking, than reported by those without childhood attention problems (relative risk [RR] = 1.53, 95% CI = 1.31–1.79). Furthermore, they were nearly twice as likely to be current smokers in adulthood compared with those without childhood attention problems (RR = 1.71, 95% CI = 1.38–2.11). Similar associations were found between components of adult executive dysfunction and adult smoking.
Discussion:
Childhood cancer and treatment are associated with subsequent deficits in attention and EF. Early detection of these deficits will allow clinicians to identify patients who are at increased risk for smoking, an important step in promoting and maintaining health in this medically vulnerable population.
doi:10.1093/ntr/ntq004
PMCID: PMC2847073  PMID: 20154054
16.  Ocular Late Effects in Childhood and Adolescent Cancer Survivors: A Report from the Childhood Cancer Survivor Studya 
Pediatric blood & cancer  2010;54(1):103-109.
Introduction
Approximately 80% of children currently survive 5 years following diagnosis of their cancer. Studies based on limited data have implicated certain cancer therapies in the development of ocular sequelae in these survivors.
Procedure
The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study investigating health outcomes of 5+ year survivors diagnosed and treated between 1970 and 1986 compared to a sibling cohort. The baseline questionnaire included questions about the first occurrence of 6 ocular conditions. Relative risks (RR) and 95% confidence intervals (CI) were calculated from responses of 14,362 survivors and 3,901 siblings.
Results
Five or more years from the diagnosis, survivors were at increased risk of cataracts (RR:10.8; 95% CI: 6.2–18.9), glaucoma (RR: 2.5; 95% CI: 1.1–5.7), legal blindness (RR: 2.6; 95% CI: 1.7–4.0), double vision (RR:4.1; 95% CI: 2.7–6.1), and dry eyes (RR: 1.9; 95% CI: 1.6–2.4), when compared to siblings. Dose of radiation to the eye was significantly associated with risk of cataracts, legal blindness, double vision, and dry eyes, in a dose-dependent fashion. Risk of cataracts were also associated with radiation 3000+ cGy to the posterior fossa (RR: 8.4; 95% CI: 5.0–14.3), temporal lobe (RR: 9.4; 95% CI: 5.6–15.6), and exposure to prednisone (RR:2.3; 95% CI:.1.6–3.4)
Conclusions
Childhood cancer survivors are at risk of developing late occurring ocular complications, with exposure to glucocorticoids and cranial radiation being important determinants of increased risk. Long-term follow-up is needed to evaluate potential progression of ocular deficits and impact on quality of life.
doi:10.1002/pbc.22277
PMCID: PMC2783513  PMID: 19774634
late effects of cancer therapy; radiation therapy; chemotherapy

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