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9556 Background: Survivors of childhood cancer have a high burden of chronic health conditions following cancer therapy, but the risk for subsequent hospitalization has not been reported. Methods: Hospitalizations during 1996–2000 among a cohort of 10,367 5-yr survivors of childhood cancer (diagnosed 1970–1986) and 2,540 siblings were ascertained. Age-and gender-stratified standardized incidence ratios (SIRs) for hospitalization were calculated using the sibling cohort and U.S. population from the National Hospital Discharge Survey (NHDS). Associations between demographic, cancer/treatment-related risk factors and non-obstetrical hospitalization among survivors were evaluated in multiple variable logistic regression models. Results: At follow-up, survivors were a mean of 20.9 yrs. from diagnosis (SD: 4.6, range: 13.3–32.2) and mean age of 28.6 yrs. (SD: 7.7, range: 13–51). Overall hospitalization rates among survivors were 1.5 times (95% CI 1.44–1.52) that of siblings and 1.2 times (95% CI 1.16–1.22) that of the U.S. general population. Increased risk of hospitalization was noted irrespective of gender, age at follow-up, or cancer diagnosis, with highest SIRs noted for male (SIR=12.7, 95% CI 9.5–15.8) and female (SIR=72.1, 95% CI 58.8–85.5) survivors aged 45–54. Females (OR=1.2, 95% CI 1.04–1.3) and survivors with a chronic health condition (OR=1.6, 95% CI 1.5–1.8) were more likely to have been hospitalized for non-obstetrical causes after adjusting for age at diagnosis, age at follow-up, cancer diagnosis, household income, insurance, and history of relapse/second malignancy. Among survivors, those with Hodgkin's lymphoma had the highest hospitalization rates for neoplastic, infectious, endocrine, pulmonary and cardiovascular causes. CNS malignancy survivors had the highest hospitalization rates for neurologic, psychological and external (e.g. traumatic) causes. Conclusions: Therapy for childhood and adolescent cancer is associated with a significant increase in subsequent hospitalization rates. Regular medical follow-up and early intervention for chronic health conditions may help to limit severe toxicity that would require hospitalization. No significant financial relationships to disclose.

Background Despite their risk for serious late sequelae, survivors of childhood cancer do not adhere to recommended medical screening guidelines. We identified treatment, survivor, physician, and contextual factors that may influence survivor adherence to recommended echocardiography and bone densitometry screening. Methods Structural equation modeling of data from the Childhood Cancer Survivor Study; 838 participants had received a diagnosis of and were treated for pediatric cancers between 1970 and 1986. Results Survivors at risk of cardiac sequelae (n = 316; mean [SD] age, 31.01 [7.40] years; age at diagnosis, 9.88 [5.88] years; and time since diagnosis, 21.14 [4.37] years) who reported more cancer-related visits (P = .01), having discussed heart disease with a physician (P ≤ .001), with a sedentary lifestyle (P = .05), and less frequent health fears (P = .05) were most likely to follow the recommended echocardiogram schedule (R2 = 23%). Survivors at risk of osteoporosis (n = 324; age, 30.20 [7.09] years; age at diagnosis, 9 .01 [5.51]years; and time since diagnosis, 21.20 [4.27] years) who reported more cancer-related visits (P = .05), were followed up at an oncology clinic (P = .01), had discussed osteoporosis with a physician (P ≤ .001), and had a lower body mass index (P = .05) were most likely to adhere to the recommended bone density screening guidelines (R2 = 26%). Symptoms and motivation influenced screening frequency in both models. Conclusions Multiple factors influence survivor adherence to screening recommendations. It is likely that tailored interventions would be more successful in encouraging recommended screening in survivors of childhood cancer than would traditional health education approaches.

BREAST CANCER IS A RECOGNIZED COMPLICATION OF chest irradiation for childhood cancer, and surveillance for breast cancer with regular clinical examination and annual screening mammography starting at age 25 years or 8 years after radiation is recommended. However, uptake of screening mammograms in this high-risk group is suboptimal, as shown in the report by Oeffinger and colleagues in this issue of JAMA. The authors examined breast cancer surveillance practices in a survey of 625 female survivors of pediatric cancer who were between 25 and 50 years and participants in the longitudinal Childhood Cancer Survivor Study (CCSS). These survivors were at a significantly increased risk of breast cancer as a result of treatment they received in the form of moderateto high-dose ( 20 Gy) irradiation to the chest for treatment of a childhood cancer (chest RT group). The women in the chest RT group were compared with 639 similarly aged CCSS participants who did not receive chest irradiation and with 712 siblings in the CCSS siblings cohort. Oeffinger et al found that 55% of the women in the chest RT group reported having a screening mammogram within the previous 2 years. Rates of screening mammography varied by age at the time of the survey, with 23.3% of women aged 25 through 39 years and 53.6% of women aged 40 through 50 years reporting a screening mammogram in the previous year. Among women in the younger group, those who reported a physician recommendation for screening were 3 times as likely to have had screening in the previous 2 years when compared with those whose physician did not recommend that they have a mammogram. In light of a recognized increased risk of breast cancer following radiation to the chest, chest irradiation is now used less frequently for the curative treatment of some pediatric cancers, which include different types of childhood cancer including Hodgkin disease, Wilms tumor, neuroblastoma, and non-Hodgkin lymphoma; however, there are an estimated 20 000 to 25 000 adult survivors of pediatric cancer older than 25 years in the United States who are in this risk category. Current Childhood Oncology Group (COG) guidelines for breast cancer surveillance after pediatric cancer in the United States recommend yearly clinical breast examination from the age of puberty until age 25 years, and then every 6 months if the survivor was treated with irradiation of at least20 Gy to mantle, minimantle, mediastinal, chest (thoracic), or axillary fields. In addition, it is recommended that these survivors have annual mammography and an adjunct breast magnetic resonance imaging (MRI) starting at age 25 years or 8 years after radiation, whichever is last. The effectiveness of the standard mammogram in detecting preinvasive and invasive breast cancer is known to be relatively poor in young women due to the density of breast tissue in this age group, increasing the importance of MRI in the detection and diagnosis of breast cancer in younger women with dense breast tissue. The estimated dose of radiation from a standard 2-view screening mammogram is approximately 3.85 mGy per mammogram. Although it is accepted that the additional dose is small compared with the higher therapeutic dose already received, it is not known to what extent repeated exposure to small doses of breast irradiation in women already at an increased risk of breast cancer may result in a significantly increased risk of second primary breast cancer. This is an important question that needs to be addressed in future studies. The generally low uptake rate of screening mammogram in a high-risk population of pediatric cancer survivors has also been highlighted in a previous study of adult survivors. Some factors associated with the uptake of breast screening including age and race/ethnicity, physician recommendation, health beliefs, and personal understanding of breast cancer risk were explored by Oeffinger et al, but economic factors were not. Thus, whether the cost of annual breast cancer screening was a factor in this cohort is not known. In comparison, among a population of 461 Australian women at an increased risk of developing hereditary breast cancer, uptake of breast screening was 89% overall, although it decreased to 77% among those

10015 Background: To improve survival in childhood CNS tumors aggressive surgical intervention, radiotherapy, and chemotherapy have been employed. Long-term survivors are at risk for a broad array of late-effects secondary to tumor location and/or therapeutic interventions. Methods: Analysis included 1,538 5-yr survivors of childhood CNS tumors (including 1,035 with Astrocytoma [AST], 306 Medulloblastoma/PNET [M/PNET], 115 Ependymoma [EP], and 82 Others). Patients, diagnosed 1970–86, had a median follow-up of 22.1 yrs (range16.1–34.6). Outcomes of mortality, second malignant neoplasm (SMN), health status, education, employment, insurance, and marital status were assessed to determine risk associated with tumor type and treatment modality including region-specific cumulative radiation (RT) dose to the CNS. Results: 307 deaths >5 yrs after diagnosis resulted in a cumulative late mortality rate of 18.2% (95% confidence interval [CI] 16.1–20.3) at 25 yrs (EP 23.3%; M/PNET 19.0%; AST 17.3%). Standardized morta...

10006 Background: Paradoxically, HL is the paradigm of treatment success, yet HL survivors are at an increased risk of premature death. We aimed to characterize risks factors associated with mortal...

9509 Background: Previous research has shown that cardiovascular disease contributes to significant morbidity and mortality among survivors of childhood and adolescent cancer. Few studies have repo...

10008 Background: Determine the proportion of female childhood cancer survivors with impaired fertility and evaluate impact of treatment on likelihood of pregnancy. Methods: 5,665 CCSS participants...

934 RISK OF BLADDER CANCER AFTER CHILDHOOD CANCER Pratik M Gurung*, Clare Frobisher, Alison Leiper, Christopher R J Woodhouse, Michael M Hawkins. London, United Kingdom, and Birmingham, United Kingdom. INTRODUCTION AND OBJECTIVE: The objectives were to estimate the risk of bladder cancer (BCa) after childhood cancer, and explore whether cases were originally treated with cyclophosphamide (CPM) or radiotherapy. METHODS: The analysis used the British Childhood Cancer Survivor Study (BCCSS), which consists of 17,981 individuals

9544 Background: Neuroblastoma (NB) survivors can develop many complications from their treatment. We evaluated long-term morbidity and mortality in a large cohort of NB survivors. Procedures: Late effects data from 5-year NB survivors diagnosed between 1970–1986 enrolled in the Childhood Cancer Survivor Study (CCSS) were collected from self-administered questionnaires. 832 survivors and 3,899 siblings were included. Treatment data were abstracted from the medical records of all survivors. Late mortality, second malignant neoplasm (SMN), and chronic health conditions were analyzed in relation to treatment factors. Results: 42 survivors (6%) died more than 5 years after their diagnosis (standardized mortality ratio [SMR]:4.8; 95% CI 3.5–6.5). Causes of death included: disease recurrence (n=23), SMN (n=6) (SMR: 8.5; 95% CI 3.1–18.4), cardiac (n=1) (SMR 2.9; 95% CI 0.04–16.0), pulmonary (n=1) (SMR 4.8; 95% CI 0.1–26.5), external causes (n=4), other and unknown (n=11). 33 developed a SMN (standardized incidence ratio [SIR] 8.6; 95% CI 5.9–12.1): thyroid (n=7), renal (n=6), soft tissue sarcomas (n=3), acute myeloid leukemia (n=2), breast cancer (n=2) and other (n=13). Exposure to radiation therapy (RT) (p=0.003) and to VP-16 (p=0.04) were significant risk factors for SMN. 38% of the survivors reported at least one chronic health condition. Compared to siblings, they were more likely to report any chronic condition (risk ratio [RR] 14.7; 95% CI, 12.4–17.6). The most common prevalent conditions included: musculoskeletal (RR 49.8; 95% CI, 27.9–88.8), endocrine (RR 36.2; 95%CI 24.1–54.5), sensory (RR 21.5; 95%CI, 14.6–31.7) and neurological (RR 13.1; 95% CI 10.8–16). A multivariable Poisson regression analysis revealed the following associations: laminectomy (RR 8.6; 95% CI 3.5- 21) and chest RT (RR 2.8; 95% CI 1.3–6.5) as risk factors for scoliosis; age < 1 year at diagnosis (RR 1.9; 95% CI 1.4–2.6) and laminectomy (RR 3.5; 95% CI 2.4–5.3) for neurological complications; for hearing loss, increasing cumulative dose of cisplatin (for ≥ 600 mg/m2 RR 52.8; 95% CI 10.2–272.5); and RT to the neck (RR 6.6; 95% CI 2.4–18) for hypothyroidism. Conclusions: NB survivors are at risk of developing chronic conditions. Long-term surveillance is required for early detection of these complications. No significant financial relationships to disclose.

9516 Background: Determine the proportion of male (M) survivors with impaired fecundity (IF). Methods: 6,555 CCSS M participants and 1,606 M siblings (S) were classified as surgically sterile (SS) for contraceptive purpose, SS for non-contraceptive purpose, IF (ongoing attempts to become pregnant for a period of one year without success or use of medication to help achieve a pregnancy), or fecund (F). Odds ratios (OR) were estimated using logistic regression, controlling for education level, marital status, age at baseline questionnaire, race/ethnicity and smoking status. Results: M were 6–29 years from cancer diagnosis (mean-16.3 years) and 15–44 years of age at the time of study (mean-25.4 years). 331 (5.0%) M or their partners were SS, 487 (7.4%) had IF and 5,737 (87.5%) were F. The OR (95% confidence interval (CI)) for being F was 0.66 (95% CI, 0.54–0.80) (pst tertile OR=1.70; 95% CI 1.19–2.43; p=0.0035; 2nd tertile OR=2.63; 95% CI 1.82–3.81; prd tertile OR=3.42; 95% CI 2.41–4.86; pst tertile OR=1.56; 95% CI 1.04–2.34; p=0.031; 2nd tertile OR= 2.22; 95% CI 1.43–3.44; p=0.00036; 3rd tertile OR=2.72;95% CI 1.74–4.25; p No significant financial relationships to disclose.

9017 Background: This study describes the frequencies of and risk factors for altered oral health and dental development in pediatric patients who have survived childhood cancer. Methods: We identified 8,522 participants and 2,831 siblings in the CCSS with information on dental health. Dental outcomes of treatment and socioeconomic-demographic (SED) data, were analyzed using univariate and multivariate logistic regression models to estimate odds ratios (OR). Results: Survivors included 4,249 females (49.9%), 7,367 white non-Hispanic (86.5%). Median age at cancer diagnosis, 6.8y (range, 0–20 y); time from diagnosis to interview, 31.4 y (range, 17–54 y). Overall, 30% of survivors self-reported ≥ 1 oral-dental abnormality: microdontia (10%), hypodontia (8%), > 5 caries (55%), root stunting (6%), enamel hypoplasia (13%), gingivitis (7%). Compared to siblings, survivors were at increased risk of ≥ 1 oral-dental abnormalities when adjusted for SED (OR = 2.0, p No significant financial relationships to disclose.

Background: Survival for ALL has improved substantially: current five-year survival rates are approximately 80% yet survivors continue to experience late medical and social effects. Objective: To report rates of mortality and second neoplasm (SN) and selected social outcomes from a large cohort of childhood ALL survivors. Methods: Five year survivors of ALL (n=4151) diagnosed < age 21, from 1970–1986 were compared to population rates or a sibling control group (n=3899) for mortality, SN, education, marriage, health insurance and employment. Results: Survivors and siblings were 53% and 48% male; median ages were 26 and 31yrs respectively. Survivors had a mean age of 6 yrs (range 0–20) at diagnosis and had a mean follow-up of 22 yrs (range 16–34). Sixty two percent received chemotherapy (CT) + radiation therapy (RT), 5.2% underwent marrow transplant with CT +/− RT, while 27% received CT only. Among 5yr survivors, 417 deaths occurred; cumulative mortality was 12% at 25 yrs. Recurrent ALL accounted for 67% of deaths, while 13% (n=55) died of SN. Standardized mortality rate (95% confidence intervals) for malignant SNs was 14.0 (10.7–17.9). Survival at 25 yrs was 94% for patients who never reported relapse and 59% for patients who reported a relapse (p Conclusion: In the largest long-term follow-up study of its kind, the CCSS cohort demonstrated a significant improvement in survival over time among 5-yr survivors of ALL with and without history of relapse. Death after cohort entry was due most commonly to ALL, although SNs contributed substantially. HS graduation rates for survivors were comparable to the sibling cohort, but the rates were significantly lower for college graduation and for marraige. Although lower than siblings, majority of survivors reported being employed and having health insurance. There was no significant difference between the survivors of relapsed and non-relapsed ALL, with respect to their socioeconomic outcomes. Rates (percentage), Age Standardized to Siblings Sibling Non-relapse Relapse p-value Relapse vs. Non * p for rows 1 & 2 HS grad 97 93 97 College grad 52 41 41 .78* Never married 21 34 46 .10 Ever employed 100 98 97 .07 Health Insurance 90 86 88 .86

Survival rates for childhood AML continue to improve. Limited data exist on the comprehensive assessment of late medical and social effects experienced by these aggressively treated individuals. This analysis includes 272 5-yr survivors of AML participating in the CCSS diagnosed ≤ age 21, between 1970–1986. AML survivors who received a blood or marrow transplant are excluded from the current analysis. Comparisons among treatment groups and to a sibling control group are age and gender adjusted. Survivors (55% female) were on average 7 yrs old at dx and 28 yrs at follow-up, 56% received chemotherapy only, 34% chemotherapy/RT. Average follow-up was 22.6 yrs (16.1–33.5). Among these 5-yr survivors, overall survival was 97% (95% CI, 94–98%) at 10 yrs and 94% (95% CI, 92–97%) at 20 yrs. Six individuals reported 8 recurrences a mean of 11.1 yrs (5.6–16.6) from diagnosis, 2 died from relapse, 1 from congestive heart failure (CHF), and 1 from a myocardial infarction (MI). All cause standardized mortality ratio was 4.7 (95% CI 2.8–7.5). Cumulative incidence of recurrent AML at 10 and 20 years was 1.8% (95% CI 0.2–3.4%) and 3.7% (95% CI 1.4–5.9%), respectively. Eight survivors reported 10 subsequent malignant neoplasms (SMN) (5 breast cancers, 3 CNS tumors, 1 ovarian tumor, 1 salivary gland tumor) a mean of 18.7 yrs (9.2–26.4) from diagnosis, 3 with a history of RT exposure. SMN cumulative incidence at 20 yrs was 1.6% (95% CI 0.02–3.3%) with a standardized incidence ratio of 3.2 (95% CI 1.4–6.0). Six cardiac events (5 CHF and 1 MI) occurred a mean of 16.4 yrs (12.8–18.4) from diagnosis, 20-yr cumulative incidence 2.4% (95% CI 0.5–4.4%). Among those aged 25 yrs or more, marriage rates were similar among AML survivors and the general U.S. population (59%), but lower compared to siblings (69%) (p

9004 Background: In cancer survivors, CHF associated with the use of anthracyclines is an important clinical complication. Risk factors for anthracycline associated cardiac toxicity, including cumulative dose, gender, and age, have been described. However, these risk factors do not fully explain the observed clinical variability. Notably, the potential role of genetic risk factors has not been studied. A recent “unifying hypothesis” postulates that the early cardiac damage is mediated mostly by oxidative stress while the more chronic type of toxicity is induced by anthracycline alcohol metabolites synthesized by carbonyl reductases (CBRs). Therefore we hypothesized that genetic polymorphisms in genes encoding for enzymes involved in oxidative stress pathways, and the metabolism of anthracyclines may impact on the risk of anthracycline-related cardiotoxicity. Methods: We conducted a nested case-control study within a cohort of 5,739 patients enrolled in the CCSS. Forty-seven cases with CHF and 195 matched controls (matched for demographics, follow-up and treatment) were genotyped for 10 genetic polymorphisms in 7 genes: catalase (CAT), GSTP, GSTT, GSTM, superoxide dismutase (SOD 1), NQO1, and CBR3. Results: In the subjects who received anthracyclines, multivariable analyses of CHF risk, adjusted for gender, smoking history, recurrence, and family history of heart disease, showed the GSTP +313A>G polymorphism was a significant risk factor, HR = 5.0, p = 0.01 for the A/G genotype vs. A/A; HR = 3.3, p = 0.19 for the G/G genotype vs. A/A. In addition, a suggested association between CBR3 V244M polymorphism and the risk of CHF after treatment with anthracyclines, HR=10.2, p=0.06 for G/G vs. A/A; HR = 4.0, p=0.18 for G/A vs. A/A was seen in an identical multivariable analysis. Conclusions: These data suggest that specific polymorphic genetic variants on a panel of candidate genes relevant to the anthracycline pharmacodynamics may modify the risk of CHF in childhood cancer survivors. Future studies to further refine the role of these novel genetic risk factors affecting a large population are warranted. No significant financial relationships to disclose.

9006 Background: The Childhood Cancer Survivor Study (CCSS) is an NIH funded project (U01-CA 55727) designed to study the effects of childhood cancer treatment on long- term survivors. Previous studies have found associations between certain cancer therapies and visual complications. Methods: The CCSS is a retrospective cohort study 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 14,362 survivors of childhood cancer and 3,901 sibling controls. Analysis determined the first occurrence of 8 visual conditions in 3 time periods: during therapy, end of therapy to 5 years post diagnosis, and greater than or equal to 5 years post diagnosis. Multivariate analyses, adjusting for current age and gender, determined the relative risks (RR) and 95% confidence interval (CI) of visual conditions by treatment exposure. Results: Survivors had statistically significant increases in the RR of cataracts, glaucoma, legal blindness, double vision, retinal condition, and dry eyes, across all time periods, when compared to siblings. During the time period of 5 or more years post-diagnosis, statistically significant positive associations were present for cataracts and other head radiation, craniospinal radiation, total body radiation, and prednisone; glaucoma and craniospinal radiation; double vision and craniospinal radiation; legally blind and other head radiation and craniospinal radiation; and dry eyes and other head radiation, total body radiation, and dexamethasone. There were no statistically significant associations between treatment factors and retinal conditions. Conclusions: Childhood cancer survivors are at risk of developing visual complications and treatment related factors are important determinants of this risk. Follow-up is needed to evaluate the impact of visual conditions on quality of life. [Table: see text] No significant financial relationships to disclose.

Introduction This analysis examined the influence of ethnicity on health care access received and planned for the future and the effect of ethnicity on health concerns in adult minority childhood cancer survivors. Methods Cross-sectional data from 77 black, 118 Hispanic, 40 Asian, and 718 non-Hispanic white (NHW) adult childhood cancer survivors. Four self-reported measures defined health care access: general contact with the health care system in the past 2 years, cancer related follow-up (CRFU) care in the past 2 years, planning a CRFU in next 2 years, and ever had a CRFU. Health locus of control variables: concern about future health, worry about cancer recurrence, and perceived parental or spousal concern about survivor9s health. Odds ratios (OR) and 95% confidence intervals (CI) were estimated (NHW = referent). Results Mean age of survivors at time of interview = 31 years (range 18-51). Asians (18%) were less likely to report ever having had a CRFU ( p Conclusions Different etiologies including internal factors, such as concern for recurrence of malignancy, as well as external factors, such as parental or spousal concern about the survivor9s health, may explain the varied patterns in access to cancer-related follow-up care in minority survivors of childhood cancer.

Hematopoietic cell transplantation (HCT) using total body irradiation (TBI) continues to be an important treatment for children with recurrent/high risk acute leukemias. Previous studies in children examining the impact of TBI have been limited by small numbers and short length of follow-up. This study compares global health status in a large cohort of long-term survivors after HCT for acute leukemia (cases) that received TBI and compares them to patients treated for leukemia who did not receive HCT (controls). Methods: Participants were part of the CCSS, a large multi-institutional study of over 14,000 long-term survivors of childhood cancer (diagnosed Results: In a multivariate model (adjusting for age at interview, sex, and race), HCT/TBI cases were 2.1 times (95% confidence interval [CI] 1.3–3.5) more likely to report adverse general health, functional impairments (odds ratio [OR] 3.6, 95% CI 2.4–5.6), activity limitations (OR 4.0, 95% CI 2.9–5.5), and pain related to their cancer diagnosis or treatment (OR 3.6, 95% CI 2.3–5.8). HCT/TBI cases were not more likely than controls to report adverse mental health or anxiety related to their cancer diagnosis. Participants were also asked about health concerns and HCT/TBI cases were 1.8 times (95% CI 1.1–2.9) more likely to report concerns about future health, 2.0 times (95% CI1.4–3.0) more likely to report concerns about fertility, but were not more likely to have concerns about their ability to obtain health or life insurance. Conclusion: Survivors of childhood leukemia who received HCT with TBI do not report more anxiety or adverse mental health status compared to survivors treated without HCT/TBI. They do, however, report an increased adverse perception of general health, functional impairments, activity limitations, pain, and more concerns regarding their future health and fertility. HCT survivors should have ongoing long-term follow-up and be monitored closely so that appropriate interventions may be provided.

8515 Background: Subsequent sarcomas (SS) in childhood cancer survivors have not been well-studied, with prior studies limited to smaller series of bone tumors. Methods: The Childhood Cancer Surviv...

9 Background: Survivors of childhood cancer experience a variety of chronic diseases, defined as physical late effects with a potential for serious disability. This analysis was conducted to determine the incidence of chronic diseases in adult survivors of childhood cancer and determine the relative risk compared to sibling controls. Methods: The Childhood Cancer Survivor Study is a retrospective cohort study tracking health outcomes of long-term survivors (> 5 years) who were diagnosed 1970–1986 and a comparison group of siblings. The incidence of chronic diseases occurring in adult (≥ 18 years of age) survivors (N=10397) and siblings (N=3034) were calculated. A severity score, using the Common Terminology Criteria for Adverse Events, v3.0 (grades 1–4), were assigned to each chronic disease. For example, grade 4 diseases included: second malignant neoplasm (excluding non-melanoma skin and thyroid cancer), myocardial infarction or coronary artery bypass surgery, heart transplant, dialysis or kidney transp...

8517 Background: Leukemia and brain tumors are the two most common cancers of childhood. This report examines the frequency of and risk factors for stroke that occur > 5 years following diagnosis a...

8536 Background: The CCSS is a retrospective cohort study designed to determine late effects in children and adolescents diagnosed with cancer. Methods: Eligibility criteria for entry into this coh...

1028 Background: We examined the influence of ethnicity and insurance coverage on healthcare access and healthy behaviors in adult childhood cancer survivors. Methods: The CCSS is a resource design...

Survivors of childhood cancer are at risk for secondary breast cancer. Other than previous chest radiation therapy, risk factors for secondary breast cancer have not been established.To identify risk factors for breast cancer among female survivors of childhood cancer.Retrospective cohort study.The Childhood Cancer Survivor Study (CCSS), a multicenter study of persons who survived more than 5 years after childhood cancer diagnosed from 1970 to 1986.Among 6068 women in the CCSS, 95 women had 111 confirmed cases of breast cancer.Standardized incidence ratios for breast cancer were calculated by using age-specific incidence rates in the general population. Breast cancer incidence was evaluated with respect to primary cancer diagnosis and therapy, age at and time since primary diagnosis, menstrual and reproductive history, and family history of cancer.Breast cancer risk was increased in survivors who were treated with chest radiation therapy (standardized incidence ratio, 24.7 [95% CI, 19.3 to 31.0]) and survivors of bone and soft-tissue sarcoma who were not treated with chest radiation therapy (standardized incidence ratios, 6.7 and 7.6, respectively). Family history of breast cancer (relative rate, 2.7 [CI, 1.3 to 5.0]) and history of thyroid disease (relative rate, 1.7 [CI, 1.1 to 2.6]) were independently associated with increased risk, and exposure to pelvic radiation was protective (relative rate, 0.6 [CI, 0.4 to 0.9]). Age at primary cancer diagnosis and menstrual and reproductive histories did not statistically significantly modify risk.This cohort has not yet attained an age at which breast cancer risk is greatest.Survivors of childhood sarcomas and those who received chest radiation therapy are at risk for secondary breast cancer. When assessing a survivor's risk, clinicians should consider primary diagnosis, previous radiation therapy, family cancer history, and history of thyroid disease.

6023 Background: Adolescence (AD) and pre-adolescence (PRE-AD) are critical physical and psychological developmental periods. The purpose of this study was to determine if the health status, health...

8523 Background: An increased risk for strokes has not been previously reported among HD survivors. This report examines the rate and risk factors for stroke in long-term survivors of HD. Methods: ...

8129 Background: Fatigue has been reported as a late effect of cancer therapy. Limited data are available assessing fatigue and sleep among large populations of long-term survivors of pediatric and adolescent cancer. Methods: The CCSS is a cohort of 5+ yr survivors diagnosed with cancer before age 21, between 1970–1986. A selected sample of CCSS participants (lymphoblastic leukemia (ALL), brain tumors (CNS), Hodgkin's disease (HD), soft-tissue sarcoma (STS), bone tumors) was surveyed regarding self-reported fatigue and sleep using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F; range 0–52; higher score=lower fatigue), the Epworth Sleepiness Scale (ESS; range 0–24; higher score=higher daytime sleepiness), and the Pittsburgh Sleep Quality Index (PSQI; range 0–21; higher score=poorer sleep quality). Results: Data were available from 981 participants (43% males, 57% females) whose mean age at diagnosis was 12.4 yrs and 33.9 yrs at follow-up. Survivors scored higher, compared to populati...

8509 Background: Survivors of childhood and adolescent malignancies are at increased risk for SMN but there are limited data regarding risks 20+ years following diagnosis. Objectives: To determine the incidence and risk factors for SMNs in a well-defined cohort of childhood cancer survivors. Methods: Among the CCSS cohort of 20,720 5-yr survivors (diagnosed 1970–86), SMNs are ascertained and verified by pathology reports. Age- and sex-standardized incidence ratios (SIR) were calculated using US Surveillance, Epidemiology and End Results (SEER) data. Results: As of June 2003, there were 914 verified SMNs among 14,352 survivors with 198,277 person years of follow-up (including 404 cases of non-melanoma skin cancer (NMSC, 4.3% 20-yr cumulative incidence). Excluding NMSC from the analyses, the overall SIR is 3.9 (95% CI 3.5, 4.2) with a 20-yr cumulative incidence of 5.2%. The 20-yr cumulative incidence of SMN, by original diagnosis: Hodgkin disease (13.9%), Bone tumor (6.6%), Soft tissue sarcoma (5.8%), CNS t...

Thyroid Dysfunction in Survivors of Hodgkin's Disease (HD): Data from the Childhood Cancer Survivor Study (CCSS)

8530 Background: Subsequent malignant neoplasms (SMNs) are a leading cause of late mortality in survivors of childhood cancer. Using the Childhood Cancer Survivor Study (CCSS) cohort, we determined the risk of carcinomas occurring as SMNs excepting breast, thyroid and skin cancers. Methods: A retrospective cohort of 14,352 five-year survivors of childhood cancers treated at 25 US and Canadian institutions was assembled. SMNs were ascertained through self-administered questionnaires and confirmed with pathology reports. Cumulative incidence, age- and gender-matched standardized incidence ratios (SIRs) were calculated. Results: In 71 individuals, 71 carcinomas of interest were found at a median age of 27 years (range 10–44 years) and a median elapsed time of 15 years (range 6–28 years) from first malignancy. Twenty-five (35%) SMNs occurred in the genitourinary system, 23 (32%) in the head and neck area, 16 (23%) in the digestive tract, 4 (6%) in the thorax and the remainder (4%) in other sites. Fifty-nine s...

Reorganisation of clinical follow-up care in England was proposed by the National Cancer Survivorship Initiative (NCSI), based on cancer type and treatment, ranging from Level 1 (supported self-management) to Level 3 (consultant-led care). The objective of this study was to provide an investigation of the risks of serious adverse health-outcomes associated with NCSI Levels of clinical care using a large population-based cohort of childhood cancer survivors. The British Childhood Cancer Survivor Study (BCCSS) was used to investigate risks of specific causes of death, subsequent primary neoplasms (SPNs) and non-fatal non-neoplastic outcomes by NCSI Level. Cumulative (excess) risks of specified adverse outcomes by 45 years from diagnosis among non-leukaemic survivors assigned to NCSI Levels 1, 2 and 3 were for: SPNs—5% (two-fold expected), 14% (four-fold expected) and 21% (eight-fold expected); non-neoplastic death—2% (two-fold expected), 4% (three-fold expected) and 8% (seven-fold expected); non-fatal non-neoplastic condition—14%, 27% and 40%, respectively. Consequently overall cumulative risks of any adverse health outcome were 21%, 45% and 69%, respectively. Despite its simplicity the risk stratification tool provides clear and strong discrimination between survivors assigned to different NCSI Levels in terms of long-term cumulative and excess risks of serious adverse outcomes.

BackgroundExposure to radiation and/or chemotherapy during cancer treatment can compromise respiratory function. We investigated the risk of long-term respiratory mortality among 5-year cancer survivors diagnosed before age 40 years using the British Childhood Cancer Survivor Study (BCCSS) and Teenage and Young Adult Cancer Survivor Study (TYACSS).MethodsThe BCCSS comprises 34 489 cancer survivors diagnosed before 15 years from 1940 to 2006 in Great Britain. The TYACSS includes 200 945 cancer survivors diagnosed between 15 years and 39 years from 1971 to 2006 in England and Wales. Standardised mortality ratios and absolute excess risks were used.FindingsOverall, 164 and 1079 respiratory deaths were observed in the BCCSS and TYACSS cohorts respectively, which was 6.8 (95% CI 5.8 to 7.9) and 1.7 (95% CI 1.6 to 1.8) times that expected, but the risks varied substantially by type of respiratory death. Greatest excess numbers of deaths were experienced after central nervous system (CNS) tumours in the BCCSS and after lung cancer, leukaemia, head and neck cancer and CNS tumours in the TYACSS. The excess number of respiratory deaths increased with increasing attained age, with seven (95% CI 2.4 to 11.3) excess deaths observed among those aged 50+ years in the BCCSS and three (95% CI 1.4 to 4.2) excess deaths observed among those aged 60+ years in the TYACSS. It was reassuring to see a decline in the excess number of respiratory deaths among those diagnosed more recently in both cohorts.ConclusionsPrior to this study, there was almost nothing known about the risks of respiratory death after cancer diagnosed in young adulthood, and this study addresses this gap. These new findings will be useful for both survivors and those involved in their clinical management and follow-up.

Background: Female survivors of childhood cancer treated with abdominal radiotherapy who manage to conceive are at risk of delivering premature and low-birthweight offspring, but little is known about whether abdominal radiotherapy may also be associated with additional complications during pregnancy and labor. We investigated the risk of developing pregnancy and labor complications among female survivors of childhood cancer in the British Childhood Cancer Survivor Study (BCCSS). Methods: Pregnancy and labor complications were identified by linking the BCCSS cohort (n = 17 980) to the Hospital Episode Statistics (HES) for England. Relative risks (RRs) of pregnancy and labor complications were calculated by site of radiotherapy treatment (none/abdominal/cranial/other) and other cancer-related factors using log-binomial regression. All statistical tests were two-sided. Results: A total of 2783 singleton pregnancies among 1712 female survivors of childhood cancer were identified in HES. Wilms tumor survivors treated with abdominal radiotherapy were at threefold risk of hypertension complicating pregnancy (relative risk = 3.29, 95% confidence interval [CI] = 2.29 to 4.71), while all survivors treated with abdominal radiotherapy were at risk of gestational diabetes mellitus (RR = 3.35, 95% CI = 1.41 to 7.93) and anemia complicating pregnancy (RR = 2.10, 95% CI = 1.27 to 3.46) compared with survivors treated without radiotherapy. Survivors treated without radiotherapy had similar risks of pregnancy and labor complications as the general population, except survivors were more likely to opt for an elective cesarean section (RR = 1.39, 95% CI = 1.16 to 1.70). Conclusions: Treatment with abdominal radiotherapy increases the risk of developing hypertension complicating pregnancy in Wilms tumor survivors, and diabetes mellitus and anemia complicating pregnancy in all survivors. These patients may require extra vigilance during pregnancy.

The British Childhood Cancer Survivor Study (BCCSS) provides the first detailed investigation of employment and occupation to be undertaken in a large population-based cohort. Previous studies have been limited by design issues such as using small numbers of survivors with specific diagnoses, and involved limited assessment of employment status and occupational level. The BCCSS includes 17,981 5-year survivors of childhood cancer. Employment status and occupational level were ascertained by questionnaire from eligible survivors (n = 14,836). Multivariate logistic regression was used to explore factors associated with employment and occupation, and to compare survivors to their demographic peers in the general population. Employment status was available for 10,257 survivors. Gender, current age, cancer type, radiotherapy, age at diagnosis and epilepsy were consistently associated with being: employed; unable to work; in managerial or non-manual occupations. Overall, survivors were less likely to be working than expected (OR (99% CI): 0.89 (0.81-0.98)), and this deficit was greatest for irradiated CNS neoplasm survivors (0.34 (0.28-0.41)). Compared to the general population, survivors were fivefold more likely to be unable to work due to illness/disability; the excess was 15-fold among CNS neoplasm survivors treated with radiotherapy. Overall survivors were less likely to be in managerial occupations than expected (0.85 (0.77-0.94)). However, bone sarcoma survivors were more likely to be in these occupations than expected (1.37 (1.01-1.85)) and also similarly for non-manual occupations (1.90 (1.37-2.62)). Survivors of retinoblastoma (1.55 (1.20-2.01)) and 'other' neoplasm group (1.62 (1.30-2.03)) were also more likely to be in non-manual occupations than expected.

Long-term adverse outcomes in survivors of childhood bone sarcoma: the British Childhood Cancer Survivor Study

BackgroundChest wall abnormalities are a poorly studied complication after treatment for childhood cancer. Chest wall abnormalities are not well-described in the literature, and little is known on the impact on daily life of survivors.MethodsWe investigated prevalence and risk factors of chest wall abnormalities in childhood cancer survivors in a nationwide, population-based cohort study (Swiss Childhood Cancer Survivor Study) with a questionnaire survey. We then interviewed a nested sample of survivors to validate types of chest wall abnormalities and understand their impact on the daily life of survivors.ResultsForty-eight of 2382 (95%CI 2–3%) survivors reported a chest wall abnormality. Risk factors were older age at cancer diagnosis (16–20 years; OR 2.5, 95%CI 1.0–6.1), lymphoma (OR 3.8, 95%CI 1.2–11.4), and central nervous system tumors (OR 9.5, 95%CI 3.0–30.1) as underlying disease, and treatment with thoracic radiotherapy (OR 2.0, 95%CI 1.0–4.2), surgery to the chest (OR 4.5, 95%CI 1.8–11.5), or chemotherapy (OR 2.9, 95%CI 1.0–8.1). The nature of the chest wall abnormalities varied and included thoracic wall deformities (30%), deformations of the spine (5%) or both (55%), and scars (10%). Chest wall abnormalities affected daily life in two thirds (13/20) of those who reported these problems and necessitated medical attention for 15 (75%) survivors.ConclusionIt is important that, during follow-up care, physicians pay attention to chest wall abnormalities, which are rare late effects of cancer treatment, but can considerably affect the well-being of cancer survivors.

Objective To determine whether modern treatments for cancer are associated with a net increased or decreased risk of death from neoplastic and non-neoplastic causes among survivors of childhood cancer. Design Population based cohort study. Setting British Childhood Cancer Survivor Study. Participants Nationwide population based cohort of 34 489 five year survivors of childhood cancer with a diagnosis from 1940 to 2006 and followed up until 28 February 2014. Main outcome measures Cause specific standardised mortality ratios and absolute excess risks are reported. Multivariable Poisson regression models were utilised to evaluate the simultaneous effect of risk factors. Likelihood ratio tests were used to test for heterogeneity or trend. Results Overall, 4475 deaths were observed, which was 9.1 (95% confidence interval 8.9 to 9.4) times that expected in the general population, corresponding to 64.2 (95% confidence interval 62.1 to 66.3) excess deaths per 10 000 person years. The number of excess deaths from all causes declined among those treated more recently; those treated during 1990-2006 experienced 30% of the excess number of deaths experienced by those treated before 1970. The corresponding percentages for the decline in excess deaths from recurrence or progression and non-neoplastic causes were 30% and 60%, respectively. Among survivors aged 50-59 years, 41% and 22% of excess deaths were attributable to subsequent primary neoplasms and circulatory conditions, respectively, whereas the corresponding percentages among those aged 60 years or more were 31% and 37%. Conclusions The net effects of changes in cancer treatments, and surveillance and management for late effects, over the period 1940 to 2006 was to reduce the excess number of deaths from both recurrence or progression and non-neoplastic causes among those treated more recently. Among survivors aged 60 years or more, the excess number of deaths from circulatory causes exceeds the excess number of deaths from subsequent primary neoplasms. The important message for the evidence based surveillance aimed at preventing excess mortality and morbidity in survivors aged 60 years or more is that circulatory disease overtakes subsequent primary neoplasms as the leading cause of excess mortality.

Survival of childhood, adolescent and young adult (CAYA) cancers has increased with progress in the management of the treatments and has reached more than 80% at 5 years. Nevertheless, these survivors are at great risk of second cancers and non-malignant co-morbidities in later life. DeNaCaPST is a non-interventional study whose aim is to organize a national screening for thyroid cancer and breast cancer in survivors of CAYA cancers. It will study the compliance with international recommendations, with the aim, regarding a breast screening programme, of offering for every woman living in France, at equal risk, an equal screening. DeNaCaPST trial is coordinated by the INSERM 1018 unit in cooperation with the LEA (French Childhood Cancer Survivor Study for Leukaemia) study’s coordinators, the long term follow up committee and the paediatric radiation committee of the SFCE (French Society of Childhood Cancers). A total of 35 centres spread across metropolitan France and la Reunion will participate. FCCSS (French Childhood Cancer Survivor Study), LEA and central registry will be interrogated to identify eligible patients. To participate, centers agreed to perform a complete “long-term follow-up consultations” according to good clinical practice and the guidelines of the SFCE (French Society of Children Cancers). As survival has greatly improved in childhood cancers, detection of therapy-related malignancies has become a priority even if new radiation techniques will lead to better protection for organs at risk. International guidelines have been put in place because of the evidence for increased lifetime risk of breast and thyroid cancer. DeNaCaPST is based on these international recommendations but it is important to recognize that they are based on expert consensus opinion and are supported by neither nonrandomized observational studies nor prospective randomized trials in this specific population. Over-diagnosis is a phenomenon inherent in any screening program and therefore such programs must be evaluated.