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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 objective 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 and 1986 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 years (range, 21.2-58.8 years) and 38.1 years (range, 18.4-62.6 years), 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 fracture during their lifetime. The prevalence of fractures was lower among survivors than among siblings, both in males (prevalence ratio, 0.87; 95% confidence interval, 0.81-0.94; P < .001) and females (prevalence ratio, 0.94; 95% confidence interval, 0.86-1.04; P = .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 = .015). Among males, only smoking history and white race were associated with an increased prevalence of fracture (P < .001).Conclusions: Findings from this study indicated that the prevalence of fractures among adult survivors did not increase compared with that of siblings. Additional studies of bone health among aging female cancer survivors may be warranted. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Treatment regimens for childhood acute lymphoblastic leukemia (ALL) contain neurotoxic agents that may interfere with neuromuscular health. In this study, the authors examined associations between neuromuscular impairments and physical function and between neuromuscular impairments and doses of vincristine and intrathecal methotrexate used to treat leukemia among survivors of childhood ALL.Methods: ALL survivors >10 years from diagnosis participated in neuromuscular performance testing. Treatment data were abstracted from medical records. Regression models were used to evaluate associations between treatment factors, neuromuscular impairments, and physical performance.Results: Among 415 survivors (median age, 35 years; age range, 21-52 years), balance, mobility, and 6-minute walk (6MW) distances were 1.3 standard deviations below age-specific and sex-specific values in 15.4%, 3.6%, and 46.5% of participants, respectively. Impairments included absent Achilles tendon reflexes (39.5%), active dorsiflexion range of motion (ROM) <5 degrees (33.5%), and impaired knee extension strength (30.1%). In adjusted models (including cranial radiation), survivors who received cumulative intrathecal methotrexate doses ≥215 mg/m(2) were 3.4 times more likely (95% confidence interval, 1.2-9.8 times more likely) to have impaired ROM than survivors who received no intrathecal methotrexate, and survivors who received cumulative vincristine doses ≥39 mg/m(2) were 1.5 times more likely (95% CI, 1.0-2.5 times more likely) to have impaired ROM than survivors who received lower cumulative doses of vincristine. Higher intrathecal methotrexate doses were associated with reduced knee extension strength and 6MW distances.Conclusions: Neuromuscular impairments were prevalent in childhood ALL survivors and interfered with physical performance. Higher cumulative doses of vincristine and/or intrathecal methotrexate were associated with long-term neuromuscular impairments, which have implications on future function as these survivors age. [ABSTRACT FROM AUTHOR]

Background: The authors 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 for lower-skill jobs.Methods: The authors created 3 mutually exclusive occupational categories for participants aged ≥ 25 years: Managerial/Professional, Nonphysical Service/Blue Collar, and Physical Service/Blue Collar. The authors examined currently employed survivors (4845) and their siblings (1727) in multivariable generalized linear models to evaluate the likelihood of being in 1 of the 3 occupational categories. Multinomial logistic regression was used among all participants to examine the likelihood of these outcomes compared to being unemployed (survivors, 6671; siblings, 2129). Multivariable linear models were used to assess survivor occupational differences by cancer-  and treatment-related variables. Personal income was compared by occupation.Results: Employed survivors were less often in higher-skilled Managerial/Professional occupations (relative risk, 0.93; 95% confidence interval 0.89-0.98) than their siblings. Survivors who were black, were diagnosed at a younger age, or had high-dose cranial radiation were less likely to hold Managerial/Professional occupations than other survivors. In multinomial models, female survivors' likelihood of being in full-time Managerial/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 3 occupational categories in models adjusted for sociodemographic variables.Conclusions: Adult childhood cancer survivors are employed in lower-skill jobs than siblings. Survivors with certain treatment histories are at higher risk for lower-skill jobs and may require vocational assistance throughout adulthood. [ABSTRACT FROM AUTHOR]

Background: Lack of health insurance is a key barrier to accessing care for chronic conditions and cancer screening. The influence of insurance type (private, public, none) on survivor-focused and general preventive health care in adult survivors of childhood cancer was examined.Methods: The Childhood Cancer Survivor Study is a retrospective cohort study of childhood cancer survivors diagnosed between 1970 and 1986. Among 8425 adult survivors, the relative risk (RR) and 95% confidence interval (CI) of receiving survivor-focused and general preventive health care were estimated for uninsured (n = 1390) and publicly insured (n = 640), compared with for the privately insured (n = 6395)Results: Uninsured survivors were less likely than those privately insured to report a cancer-related visit (adjusted RR, 0.83; 95% CI, 0.75-0.91) or a cancer center visit (adjusted RR, 0.83; 95% CI, 0.71-0.98). Uninsured survivors had lower levels of utilization in all measures of care in comparison with privately insured. In contrast, publicly insured survivors were more likely to report a cancer-related visit (adjusted RR, 1.22; 95% CI, 1.11-1.35) or a cancer center visit (adjusted RR, 1.41; 95% CI, 1.18-1.70) than were privately insured survivors. Although publicly insured survivors had similar utilization of general health examinations, they were less likely to report a Papanicolaou test or a dental examinationsConclusions: Among this large, socioeconomically diverse cohort, publicly insured survivors utilize survivor-focused health care at rates at least as high as survivors with private insurance. Uninsured survivors have lower utilization of both survivor-focused and general preventive health care. [ABSTRACT FROM AUTHOR]

Background: Osteosarcoma survivors have received significant chemotherapy and have undergone substantial surgeries. Their very long-term outcomes (20 year) are reported here.Methods: The authors assessed the long-term outcomes of 733 5-year survivors of childhood osteosarcoma diagnosed from 1970 to 1986 to provide a comprehensive evaluation of medical and psychosocial outcomes for survivors enrolled in 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 psychosocial factors. Outcomes of osteosarcoma survivors were compared with 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% confidence interval [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<.01). Overall, 86.9% of osteosarcoma survivors experienced at least 1 chronic medical condition, and >50% experienced ≥2 conditions. Compared with survivors of other cancers, osteosarcoma survivors did not differ in their reported general health status (odds ratio [OR], 0.9; 95% CI, 0.7-1.2), but were more likely to report an adverse health status in at least 1 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 of experiencing chronic medical conditions and adverse health status. Survivors warrant life-long follow-up. [ABSTRACT FROM AUTHOR]

Background: Pediatric cancer survivors who were treated before routine hepatitis C virus (HCV) screening of blood donors in 1992 have an elevated risk of transfusion-acquired HCV.Methods: To assess long-term pediatric cancer survivors' knowledge of HCV testing and blood transfusion history, a questionnaire was administered to 9242 participants in the Childhood Cancer Survivor Study who are at risk for transfusion-acquired HCV after cancer therapy from 1970 to 1986.Results: More than 70% of survivors reported either no prior HCV testing (41%) or uncertainty about testing (31%), with only 29% reporting prior testing. One half recalled having a treatment-related blood transfusion; those who recalled a transfusion were more likely to report HCV testing (39%) than those who did not (18%) or were unsure (20%). In multivariate models, survivors who reported no prior HCV testing were more likely to be older (odds ratio [OR] per 5-year increase, 1.1; 95% confidence interval [CI], 1.0-1.1) and to report no care at a cancer center within the past 2 years (OR, 1.2; 95% CI, 1.0-1.4), no cancer treatment summary (OR, 1.3; 95% CI, 1.2-1.5), and no transfusions (OR, 2.6; 95% CI, 2.3-3.0) or uncertainty about transfusions (OR, 2.2; 95% CI, 1.9-2.6), and less likely to be racial/ethnic minorities (OR, 0.9; 95% CI, 0.8-1.0) or survivors of acute myeloid leukemia (OR, 0.7; 95% CI, 0.5-1.0).Conclusions: Many pediatric cancer survivors at risk for transfusion-acquired HCV are unaware of their transfusion history and prior testing for HCV and would benefit from programs to increase HCV knowledge and screening. [ABSTRACT FROM AUTHOR]

Background: The current study was performed to describe frequencies and risk factors of altered oral health and odontogenesis in childhood cancer survivors.Methods: In total, 9308 survivors who were diagnosed between 1970 and 1986 and 2951 siblings from the Childhood Cancer Survivor Study completed a survey that contained oral-dental health information. The authors analyzed treatment impact, socioeconomic data, and patient demographics on dental outcomes using univariate and multivariate logistic regression models to estimate odds ratios (ORs).Results: In multivariate analysis, survivors were more likely to report microdontia (OR, 3.0; 95% confidence interval [95% CI], 2.4-3.8), hypodontia (OR, 1.7; 95% CI, 1.4-2.0), root abnormalities (OR, 3.0; 95% CI, 2.2-4.0), abnormal enamel (OR, 2.4; 95% CI, 2.0-2.9), teeth loss>or=6 (OR, 2.6; 95% CI, 1.9-3.6), severe gingivitis (OR, 1.2; 95% CI, 1.0-1.5), and xerostomia (OR, 9.7; 95% CI, 4.8-19.7). Controlling for chemotherapy and socioeconomic factors, radiation exposure of >or=20 Gray to dentition was associated significantly with an increased risk of >or=1 dental abnormality. Dose-dependent alkylating agent therapy significantly increased the risk of >or=1 anatomic/developmental dental abnormalities in survivors who were diagnosed at age<5 years (OR, 1.7, 2.7, and 3.3 for alkylating agent scores of 1, 2, and 3, respectively).Conclusions: Radiation and chemotherapy were independent risk factors for adverse oral-dental sequelae among childhood cancer survivors. The authors concluded that patients who received receiving alkylating agents at age<5 years should be closely monitored. [ABSTRACT FROM AUTHOR]

Background: Children who receive high-dose radiotherapy to the hypothalamic-pituitary (H-P) axis may be at risk for both early and late puberty. To the authors' knowledge, data regarding the risk of altered timing of menarche after higher dose radiotherapy (RT), as used in the treatment of central nervous system (CNS) tumors, are limited.Methods: The authors evaluated 235 female survivors of CNS tumors, diagnosed between 1970 and 1986, and >1000 sibling controls who were participants in the Childhood Cancer Survivor Study, and provided self-reported data concerning age at menarche.Results: Survivors of CNS tumors were more likely to have onset of menarche before age 10 years compared with their siblings (11.9% vs 1.0%) (odds ratio [OR], 14.1; 95% confidence interval [95% CI], 7.0-30.9). Of the 138 survivors who received RT to the H-P axis, 20 (14.5%) had onset of menarche before age 10 years, compared with 4.3% of those who did not receive RT (OR, 3.8; 95% CI, 1.2-16.5). Age 50 gray OR, 9.0; 95% CI, 2.3-59.5) and spinal RT conferred an increased risk of late menarche, as did older age (>10 years) at the time of diagnosis (OR, 3.0; 95% CI, 1.3-7.0).Conclusions: Survivors of CNS tumors are at a significantly increased risk of both early and late menarche associated with RT exposure and age at treatment. [ABSTRACT FROM AUTHOR]

Background: : Participation in physical activity is important for childhood cancer survivors, because inactivity may compound cancer/treatment-related late effects. However, some survivors may have difficulty participating in physical activity, and these individuals need to be identified so that risk-based guidelines for physical activity, tailored to specific needs, can be developed and implemented. The objectives of the current study were to document physical activity patterns in the Childhood Cancer Survivor Study (CCSS) cohort, to compare the physical activity patterns with siblings in the CCSS and with a population-based sample from the Behavioral Risk Factor Surveillance System, and to evaluate associations between diagnosis, treatment, and personal factors in terms of the risk for an inactive lifestyle.Methods: : Percentages of participation in recommended physical activity were compared among survivors, siblings, and population norms. Generalized linear models were used to evaluate the associations between cancer diagnosis and therapy, sociodemographics, and the risk for an inactive lifestyle.Results: : Participants included 9301 adult survivors of childhood cancer and 2886 siblings. Survivors were less likely than siblings (46% vs 52%) to meet physical activity guidelines and were more likely than siblings to report an inactive lifestyle (23% vs 14%). Medulloblastoma (35%) and osteosarcoma (27%) survivors reported the highest levels of inactive lifestyle. Treatments with cranial radiation or amputation were associated with an inactive lifestyle as were being a woman, black race, older age, lower educational attainment, underweight or obese status, smoking, and depression.Conclusions: : Childhood cancer survivors were less active than a sibling comparison group or an age- and sex-matched population sample. Survivors who are at risk for an inactive lifestyle should be considered high priority for developing and testing of intervention approaches. Cancer 2009. (c) 2009 American Cancer Society. [ABSTRACT FROM AUTHOR]

Background: Although physical activity may modify the late effects of childhood cancer treatment, from 20% to 52% of adult survivors are sedentary. The authors of this report sought to identify modifiable factors that influence survivors' participation in physical activity.Methods: Structural equation modeling of data were derived from the Childhood Cancer Survivors Study of adult survivors (current mean age, 30.98 years; mean years since diagnosis, 23.74; mean age at diagnosis, 9.25 years) who were diagnosed between 1970 and 1986.Results: Approximately 40% of the variance in male survivors' recent participation versus nonparticipation in physical activity was explained directly and/or indirectly by self-reported health fears (P = .01), perceived primary-care physician (PCP) expertise (P = .01), baseline exercise frequency (P < or = .001), education level (P = .01), self-reported stamina (P = .01), cancer-related pain (P < or = .001), fatigue (P < or = .001), age at diagnosis (P = .01), cancer-related anxiety (P < or = .001), motivation (P = .01), affect (P = .01), and discussion of subsequent cancer risk with the PCP (P < or = .001) (N = 256; chi-square test statistic = 53.38; degrees of freedom [df] = 51; P = .38, Comparative Fit Index [CFI] = 1.000; Tucker Lewis Index [TLI] = 1.000; root mean square of approximation [RMSEA] = 0.014; weighted root mean square residual [WRMR] = 0.76). Thirty-one percent of the variance in women' recent physical activity participation was explained directly and/or indirectly by self-reported stamina (P < or = .001), fatigue (P = .01), baseline exercise frequency (P = .01), cancer-related pain (P < or = .001), cancer-related anxiety (P = .01), recency of visits with PCP (<0.001), quality of interaction with the PCP (P = .01), and motivation (P < or = .001; N = 366; chi-square test statistic = 67.52; df = 55; P = .12; CFI = 0.98; TLI = 0.98; RMSEA = 0.025; WRMR = 0.76).Conclusions: Gender-tailored intervention strategies in which providers specifically target motivation, fear, and affect may support physical activity in childhood cancer survivors. [ABSTRACT FROM AUTHOR]

Background: Childhood cancer survivors who retain ovarian function after completing cancer treatment are at increased risk of developing premature menopause, defined as cessation of menses before age 40 years. However, published data pertaining to the risk and frequency of premature menopause are limited.Methods: We assessed the incidence of and risk factors for premature menopause in 2819 survivors of childhood cancer who were older than 18 years and were participants in the multicenter Childhood Cancer Survivor Study (CCSS). The comparison group was 1065 female siblings of participants in the CCSS. A multiple Poisson regression model was constructed to determine risk factors for nonsurgical premature menopause. All statistical tests were two-sided.Results: A total of 126 childhood cancer survivors and 33 control siblings developed premature menopause. Of these women, 61 survivors (48%) and 31 siblings (94%) had surgically induced menopause (rate ratio [RR] = 0.8, 95% confidence interval [CI] = 0.52 to 1.23). However, the cumulative incidence of nonsurgical premature menopause was higher for survivors than for siblings (8% versus 0.8%; RR = 13.21, 95% CI = 3.26 to 53.51; P<.001). A multiple Poisson regression model showed that risk factors for nonsurgical premature menopause included attained age, exposure to increasing doses of radiation to the ovaries, increasing alkylating agent score (based on number of alkylating agents and cumulative dose), and a diagnosis of Hodgkin lymphoma. For survivors who were treated with alkylating agents plus abdominopelvic radiation, the cumulative incidence of nonsurgical premature menopause approached 30%.Conclusions: The results of this study will facilitate counseling current survivors about their future risk of premature menopause and aid in designing new regimens that seek to diminish late ovarian toxicity. [ABSTRACT FROM AUTHOR]

OBJECTIVES: This study explored the risk of childhood acute lymphoblastic leukemia (ALL) associated with participation by household members in hobbies or other home projects involving organic solvents. METHODS: Participants in this case-control study were 640 subjects with ALL and 640 matched controls. RESULTS: Childhood ALL was associated with frequent (> 4 times/month) exposure to model building (odds ratio [OR] = 1.9; 95% confidence interval [95% CI] = 0.7, 5.8) and artwork using solvents (OR = 4.1; 95% CI = 1.1, 15.1). We also found elevated risk (OR = 1.7; 95% CI = 1.1, 2.7) among children whose mothers lived in homes painted extensively (> 4 rooms) in the year before the children's birth. CONCLUSIONS: In this exploratory study, substantial participation by household members in some common household activities that involve organic solvents was associated with elevated risks of childhood ALL. [ABSTRACT FROM AUTHOR]

Background: Whether parental drinking and smoking during pregnancy are associated with an increased risk of cancer in offspring is controversial. There are some indications that maternal alcohol consumption is associated with an elevated risk of acute myeloid leukemia (AML) appearing in very young children. Evidence for an association between maternal smoking during pregnancy and risk of leukemia in offspring has been inconsistent.Purpose: Using data from a Children's Cancer Group case-control study, we evaluated relationships between infant leukemia risk and parental alcohol consumption and/or cigarette smoking during pregnancy or during the month prior to it.Methods: Three hundred two leukemia cases (203 acute lymphoid leukemias [ALLs], 88 AMLs, and 11 other leukemia types) diagnosed in children at 18 months of age or younger and 558 individually matched, regional (i.e., same telephone area code and exchange number) controls were included in the analysis. Information concerning parental alcohol consumption and smoking behavior during the index pregnancy and during the month prior to it was collected by telephone interviews with the mothers of all case and control subjects and the fathers of 250 case and 361 control subjects. Odds ratios (ORs) were used to measure the risk of infant leukemia associated with parental smoking and drinking; tests for trend were used to assess dose-response relationships. The data were analyzed further after stratifying the leukemia cases according to histologic and morphologic types. Reported P values are from two-sided tests of statistical significance.Results: Maternal drinking during pregnancy (compared with not drinking) was associated with ORs of 1.43 (95%) confidence interval [CI] = 1.00-2.04) for ALL and 2.64 (95% CI = 1.36-5.06) for AML. A dose-response relationship was observed for total maternal alcohol consumption during pregnancy and risk of AML (P < .01). Alcohol-related risk appeared to be most pronounced for children who developed AML with a morphology of M1 (myeloblastic with minimal maturation) or M2 (myeloblastic with maturation (OR = 7.62; 95% CI = 2.03-28.64). Paternal alcohol consumption did not confer an increased risk of infant leukemia. Maternal smoking during pregnancy (compared with not smoking) was negatively associated with infant leukemia risk (OR = 0.66 and 95% CI = 0.46-0.94 for total leukemia; OR = 0.45 and 95% CI = 0.21-0.96 for AML), whereas paternal smoking 1 month prior to pregnancy (compared with not smoking during the same period) was related to an elevated risk of ALL (OR = 1.56; 95% CI = 1.03-2.36).Conclusions: Maternal alcohol consumption during pregnancy increases the risk of infant leukemia, especially AML. Maternal smoking, however, does not elevate risk for either AML or ALL.Implications: The data suggest that in utero exposure to alcohol may contribute to leukemogenesis involving myeloid cells. [ABSTRACT FROM AUTHOR]

Objective: To determine the impact of treatment on scholastic performance in the first cohort of survivors of childhood acute lymphoblastic leukemia who are old enough to have completed their educational experience.Design: Retrospective cohort study.Setting: Twenty-three institutions in the Childrens Cancer Group.Subjects: A total of 593 adult survivors of childhood acute lymphoblastic leukemia and 409 sibling controls.Outcome Measures: Enrollment in special programs, grades during high school, graduation from high school, college admission, and college graduation.Results: After diagnosis, survivors were more likely than their sibling controls to enter a special education (relative risk [RR] = 3.4; P < .01) or a learning disabled (RR = 3.6; P < .01) program, while just as likely to enter gifted and talented programs (RR = 1.0). The risk associated with special education and learning disabled programs increased with increasing dose of cranial radiotherapy. Despite these problems, survivors generally had the same probability as their siblings of finishing high school, entering college, and earning a bachelor's degree. However, survivors treated with 24 Gy and those diagnosed before 6 years of age were less likely to enter college (RR = 0.67 and 0.6, respectively; P < .01).Conclusions: This large study demonstrates that childhood acute lymphoblastic leukemia survivors have a greater likelihood of being placed in special education or learning disabled programs than their siblings, but that most are able to overcome these problems. Dose of cranial radiotherapy and age at diagnosis are the most important education-related risk factors. [ABSTRACT FROM AUTHOR]