Siblings Of Survivors Research Articles

Financial hardship among siblings of long-term survivors of childhood cancer: A Childhood Cancer Survivor Study (CCSS) report.

10048 Background: Siblings of children with cancer may experience adverse household economic and psychosocial impacts during and after treatment. While many long-term survivors of childhood cancer experience financial hardship, financial outcomes of siblings in later adulthood are unknown. Methods: We surveyed randomly selected nearest age siblings of survivors (aged 18-64y) enrolled in the CCSS to estimate the prevalence of financial hardship, using 20 items adapted from validated national surveys grouped into 3 domains (material, psychological, behavioral). We calculated the prevalence of reporting any hardship within each domain. Multivariable logistic regression estimated associations between sibling sociodemographic characteristics and each domain of hardship. For individual financial hardship items with a matching item in the contemporaneous National Health Interview Survey (n = 21,271) or Behavioral Risk Factor Surveillance System (n = 259,901), we compared siblings with national survey respondents aged 18-64, calculating adjusted prevalence ratios to sample-weighted responses, adjusted for sex, race, ethnicity, household income, education, and marital status. Results: 1,008 siblings participated (of 1,590 approached; 63%) with median age of 46y (IQR 39–53y). Siblings were 57% female, 89% non-Hispanic White, 69% college-educated, and 74% married. The prevalence of reporting any material, psychological, and behavioral hardship among siblings was 34%, 28%, and 23%, respectively. Sibling factors associated with reporting material financial hardship included: female sex (OR 1.7, 95% CI 1.2–2.4), age (30–39y vs 21–29y: OR 2.61, 95% CI 1.1–6.5), household income ($50,000–$74,999 vs ≥$75,000: OR 2.3, 95% CI 1.4–3.6), lack of health insurance (OR 2.4, 95% CI 1.1–5.1), presence of severe/disabling chronic medical conditions (OR 1.7, 95% CI 1.1–2.8), out-of-pocket medical expenses ≥10% of income (vs < 10%: OR 4.9, 95% CI 1.9–12.3), and increased non-medical/non-home debt (for example, $25,000–$49,999 vs none: OR 5.2, 95% CI 3.2–8.6). Associations with psychological and behavioral hardship were similar. Compared with national survey respondents, siblings were more likely to report financial hardship on several individual items: difficulty paying medical bills (PR 1.2, 95% CI 1.0–1.4), worries about bills (PR 1.1, 95% CI 1.1–1.2), foregoing medical care (PR 1.3, 95% CI 1.0–1.6) and dental care (PR 1.4, 95% CI 1.2–1.6) due to cost, and worries about affording nutritious foods (PR 1.7, 95% CI 1.5–2.0). Conclusions: Adult siblings of childhood cancer survivors are more likely to experience multiple aspects of financial hardship than US adults in the general population, suggesting that childhood cancer may have life-long impact on siblings. Increased support for families across the trajectory of cancer treatment may help prevent or reduce financial hardship.

Cumulative burden of late, major surgical intervention in survivors of childhood cancer: a report from the Childhood Cancer Survivor Study (CCSS) cohort.

Multimodal cancer therapy places childhood cancer survivors at increased risk for chronic health conditions, subsequent malignancies, and premature mortality as they age. We aimed to estimate the cumulative burden of late (>5 years from cancer diagnosis), major surgical interventions among childhood cancer survivors, compared with their siblings, and to examine associations between specific childhood cancer treatments and the burden of late surgical interventions. We analysed data from the Childhood Cancer Survivor Study (CCSS), a retrospective cohort study with longitudinal prospective follow-up of 5-year survivors of childhood cancer (diagnosed before age 21 years) treated at 31 institutions in the USA, with a comparison group of nearest-age siblings of survivors selected by simple random sampling. The primary outcome was any self-reported late, major surgical intervention (defined as any anaesthesia-requiring operation) occurring 5 years or more after the primary cancer diagnosis. The cumulative burden was assessed with mean cumulative counts (MCC) of late, major surgical interventions. Piecewise exponential regression models with calculation of adjusted rate ratios (RRs) evaluated associations between treatment exposures and late, major surgical interventions. Between Jan 1, 1970, and Dec 31, 1999, 25 656 survivors were diagnosed (13 721 male, 11 935 female; median follow-up 21·8 years [IQR 16·5-28·4]; median age at diagnosis 6·1 years [3·0-12·4]); 5045 nearest-age siblings were also included as a comparison group. Survivors underwent 28 202 late, major surgical interventions and siblings underwent 4110 late, major surgical interventions. The 35-year MCC of a late, major surgical intervention was 206·7 per 100 survivors (95% CI 202·7-210·8) and 128·9 per 100 siblings (123·0-134·7). The likelihood of a late, major surgical intervention was higher in survivors versus siblings (adjusted RR 1·8, 95% CI 1·7-1·9) and in female versus male survivors (1·4; 1·4-1·5). Survivors diagnosed in the 1990s (adjusted RR 1·4, 95% CI 1·3-1·5) had an increased likelihood of late surgery compared with those diagnosed in the 1970s. Survivors received late interventions more frequently than siblings in most anatomical regions or organ systems, including CNS (adjusted RR 16·9, 95% CI 9·4-30·4), endocrine (6·7, 5·2-8·7), cardiovascular (6·6, 5·2-8·3), respiratory (5·3, 3·4-8·2), spine (2·4, 1·8-3·2), breast (2·1, 1·7-2·6), renal or urinary (2·0, 1·5-2·6), musculoskeletal (1·5, 1·4-1·7), gastrointestinal (1·4, 1·3-1·6), and head and neck (1·2, 1·1-1·4) interventions. Survivors of Hodgkin lymphoma (35-year MCC 333·3 [95% CI 320·1-346·6] per 100 survivors), Ewing sarcoma (322·9 [294·5-351·3] per 100 survivors), and osteosarcoma (269·6 [250·1-289·2] per 100 survivors) had the highest cumulative burdens of late, major surgical interventions. Locoregional surgery or radiotherapy cancer treatment were associated with undergoing late surgical intervention in the same body region or organ system. Childhood cancer survivors have a significant burden of late, major surgical interventions, a late effect that has previously been poorly quantified. Survivors would benefit from regular health-care evaluations aiming to anticipate impending surgical issues and to intervene early in the disease course when feasible. US National Institutes of Health, US National Cancer Institute, American Lebanese Syrian Associated Charities, and St Jude Children's Research Hospital.

Questionnaire- and linkage-based outcomes in Dutch childhood cancer survivors: Methodology of the DCCSS LATER study part 1.

Childhood cancer survivors are at risk for developing long-term adverse health outcomes. To identify the risk of and risk factors for specific health outcomes, well-established cohorts are needed with detailed information on childhood cancer diagnosis, treatment, and health outcomes. We describe the design, methodology, characteristics, and data availability of the Dutch Childhood Cancer Survivor Study LATER cohort (1963-2001) part 1; questionnaire and linkage studies. The LATER cohort includes 5-year childhood cancer survivors, diagnosed in the period 1963-2001, and before the age of 18 in any of the seven former pediatric oncology centers in the Netherlands. Information on health outcomes from survivors and invited siblings of survivors was collected by questionnaires and linkages to medical registries. In total, 6165 survivors were included in the LATER cohort. Extensive data on diagnosis and treatment have been collected. Information on a variety of health outcomes has been ascertained by the LATER questionnaire study and linkages with several registries for subsequent tumors, health care use, and hospitalizations. Research with data of the LATER cohort will provide new insights into risks of and risk factors for long-term health outcomes. This can enhance risk stratification for childhood cancer survivors and inform surveillance guidelines and development of interventions to prevent (the impact of) long-term adverse health outcomes. The data collected will be a solid baseline foundation for future follow-up studies.

Employment status and occupational positions of childhood cancer survivors from Denmark, Finland and Sweden: A Nordic register-based cohort study from the SALiCCS research programme.

SummaryBackgroundA childhood cancer diagnosis and late effects of treatment may affect survivors’ possibilities of employment or highly skilled occupations later in life. In this study, we compared the employment and occupational status of childhood cancer survivors with population comparisons and siblings.MethodsIn a cohort study based on Nordic registers, we identified 10 461 survivors of childhood cancer diagnosed before age 20 years in Denmark, Finland and Sweden since 1971. Survivors were compared with 48 928 population comparisons matched to survivors by age, sex and geographical region and 12 605 siblings of survivors. Annual outcome information on employment, unemployment, health-related unemployment and occupational position was obtained from the statistical institutes between 1980-2017 and assessed in multivariate logistic regression analyses from age 30 onwards.FindingsBy 30 years of age, 9.2% (95% CI, 8.6-9.9%) of survivors were unemployed for health reasons. Childhood cancer survivors had considerably higher odds of health-related unemployment at ages 30, 40 and 50 than population comparisons (ORage30, 2.57; 95% CI, 2.35-2.81) and siblings (ORage30, 2.50; 95% CI, 2.15-2.90). We observed no large difference in unemployment unrelated to health or in occupational position. Health-related unemployment was particularly pronounced among survivors of central nervous system tumours and survivors diagnosed below 15 years of age.InterpretationSurvivors at risk of health-related unemployment should be offered comprehensive survivorship care and interventions for obtaining and maintaining suitable employment.FundingNordForsk [76111], the Danish Childhood Cancer Foundation [2016-0293], Aarhus University [43239402], the Swedish Childhood Cancer Foundation [PR2020-0130] and [OB2019-0003], Tømrermester Jørgen Holm og Hustru Elisa F. Hansens Mindelegat [20088] and the Swiss National Science Foundation to LM [P2LUP3_175288].

Surviving a mass shooting

We use data on all middle and high school aged children who survived a mass shooting incident on July 22, 2011 in Utøya, Norway, to understand how such events affect survivors, their families, and their peers. Using a difference-in-differences design to compare survivors to a matched control group, we find that in the short run children who survive have substantially lower GPA (nearly 0.5 SD) and increased utilization of health care services and more mental health diagnoses. In the medium run, survivors have fewer years of schooling completed and lower labor force participation. Parents and siblings of survivors are also impacted, experiencing substantial increases in doctor visits and mental health diagnoses. However, there appear to be limited impacts on school aged peers of survivors. While this event affected the entire country, we show that survivors and their families bear significant costs despite robust social safety nets and universal access to healthcare.

Health-related and cancer risk concerns among siblings of childhood cancer survivors: a report from the Childhood Cancer Survivor Study (CCSS).

To characterize the prevalence and predictors of concerns regarding future health and cancer risk among siblings of childhood cancer survivors. This study reports longitudinal data (baseline and follow-up) from 3969 adult siblings (median age = 29 [range 18-56] years) of long-term survivors of childhood cancer (median time since diagnosis 19.6 [9.6-33.8] years). Self-reported future health and cancer risk concerns (concerned vs not concerned) were assessed. Demographics and health data reported by both the siblings and their matched cancer survivors were examined as risk factors for health concerns using multivariable logistic regression. Percentage of siblings reporting future health and cancer risk concerns, respectively, decreased across decade of survivors' diagnosis: 1970s (73.3%; 63.9%), 1980s (67.2%; 62.6%), and 1990s (45.7%; 52.3%). Risk factors associated with future health concerns included sibling chronic health conditions (grade 2 Odds Ratio [OR]=1.57, 95% CI: 1.12-2.20; grades 3-4 OR=1.86, 95% CI: 1.18-2.94; compared to less than grade 2). Risk factors associated with future cancer concerns included sibling chronic health conditions (grade 2 OR=1.43, 95% CI: 1.05-1.94; grades 3-4 OR=1.64, 95% CI: 1.09-2.47; compared to less than grade 2). Sibling concerns regarding future health and cancer have diminished in recent decades. There are subgroups of siblings that are at-risk for future health and cancer risk concerns. Routine screening of concerns in at-risk siblings of survivors of childhood cancer may benefit the siblings of cancer survivors. These individuals may benefit from early interventions during diagnosis and treatment of their siblings.

Health and cancer concerns among siblings of childhood cancer survivors: A report from the Childhood Cancer Survivor Study (CCSS).

12117 Background: Siblings of long-term survivors of childhood cancer can be at risk for persistent concerns regarding their future health and risk for cancer. We examined self-perceived future health and cancer risk concerns among such siblings. Methods: 3,969 siblings (median age 29 [range 18–56] years) of 5+ year matched pair cancer survivors (n= 3,969; age 25 [6–48] years; time since diagnosis 19.6 [9.6-33.8] years) in the CCSS self-reported physical/psychosocial problems, including concerns regarding future health and cancer risk (dichotomized as concerned vs not concerned). Chronic health conditions (CHC) were graded using the Common Terminology Criteria for Adverse Events system: mild (grade 1), moderate (grade 2), severe/disabling (grade 3),or life-threatening (grade 4). Sibling demographics, their matched survivor’s diagnosis, era and treatment components, complications (death, relapse, disfigurement) as well as self-reported health status and CHCs for siblings and survivors were examined as potential risk factors for concern using multivariable logistic regression. Adjusted odds ratios (OR) and 95% confidence intervals (CI) are reported. Results: The prevalence of siblings reporting concerns regarding health and cancer risk decreased based on decades of matched survivor diagnosis: 1970-79 (73.3%; 63.9%), 1980-89 (67.2%; 62.6%), 1990-99 (45.7%; 52.3%). Risk factors for concerns included sibling poor/fair current health (future health OR 3.65, 95% CI 2.37-5.62; cancer risk OR 1.54, 1.12-2.13) compared to good/very good/excellent health. Sibling grade 2 (future health OR 1.46, 1.23-1.74; cancer risk OR 1.20, 1.01-1.42) or grade 3-4 CHCs (future health OR 1.37, 1.09-1.71; cancer risk OR 1.28, 1.03-1.58) were associated with greater concerns compared to those with less than grade 2 CHCs. Survivor treatment with chemotherapy/radiation was associated with elevated cancer risk concerns (OR 1.51, 1.13-2.02) compared to surgery/no therapy. Siblings of survivors with grade 3-4 CHCs (OR 1.35, 1.12-1.63) had greater future health concerns compared to those with less than grade 2 CHCs. Sibling bereavement was a risk factor for future health (OR 1.45, 1.04-2.03) and cancer risk (OR 1.44, 1.05-1.99) concerns. Conclusions: The prevalence of sibling concerns regarding future health and cancer have diminished in more recent decades. Subgroups of siblings are at-risk for concerns over future health and cancer risk, partially determined by medical characteristics of their survivor and their own health status.

Childhood Sexual Abuse: Sibling Perspectives.

Despite a recent focus highlighting the systemic impact of childhood sexual abuse (CSA), the needs of nonabused siblings have been largely overlooked. This interpretative phenomenological analysis study explored the lived experience of nonabused adult siblings of survivors of CSA. Semistructured interviews were undertaken with five adult siblings who were, or had been attending a support service. Emergent themes demonstrated the personal and relational impact of CSA on siblings which were captured across five domains: trying to make sense of it all, struggling to provide support, managing the impact on the wider family, feeling silenced and finding a voice, and rescripting the future. Participants struggled to make sense of their sibling's experience, questioning their own memories of happy childhoods, often in the face of limited information about what happened. The impact of the sexual abuse not only affected the sibling relationship but was compounded by the distress of other family members, particularly parents. Participants reported feeling a lack of reciprocity in terms of their own support needs and described ongoing issues arising from the sexual abuse that they believed would likely continue for the rest of their lives. How siblings can be supported through psychoeducation and family therapy is discussed, both for their own needs and those of the entire family.

Mental health of long-term survivors of childhood and young adult cancer: A systematic review.

Childhood cancer is increasing in prevalence whilst survival rates are improving. The prevalence of adult survivors of childhood cancer is consequently increasing. Many survivors suffer long-term consequences of their cancer treatment. Whilst many of these are well documented, relatively little is known about the mental health of survivors of childhood cancer. This article aimed to describe the prevalence and spectrum of mental health problems found in adult survivors of childhood cancer using a systematic review methodology. Our review included 67 articles, describing a number of problems, including depression, anxiety, behavioural problems and drug misuse. Factors increasing the likelihood of mental health problems included treatment with high-dose anthracyclines, cranial irradiation, diagnoses of sarcoma or central nervous system tumours and ongoing physical ill health. There were numerous limitations to the studies we found, including use of siblings of survivors as a control group, self-report methodology and lack of indications for prescriptions when prescribing data were used. This review has identified many mental health problems experienced by survivors of childhood cancer; however, the exact incidence, prevalence and risk-factors for their development remain unclear. Further work to identify childhood cancer patients who are at risk of developing late mental health morbidity is essential.

Quality of Life Following Childhood Bacterial Meningitis in Luanda, Angola

BackgroundSurvivors of childhood bacterial meningitis (BM) from low-income countries are at increased risk of sequelae. How BM survivors’ daily life is affected in the developing world, is not known. We aimed to investigate the quality of life among pediatric survivors of BM in Luanda, Angola assessing both physical and psychosocial health-related quality of life (HRQOL).MethodsSurvivors from two BM treatment trials (ISRCTN62824827; NCT01540838) from Luanda Children’s Hospital were called to follow-up visits in January 2017 with a median duration of 26 months after BM. We administered Pediatric Quality of Life InventoryTM (PedsQLTM) 4.0 Generic Core Scales and Infant Scales, designed to measure HRQOL in children, to patients and/or parents. The generic core scales were administered to 64 and 32 families, and the infant scores to 8 and 3 care-givers of patients and controls, respectively. We used age-appropriate versions of the scales. We calculated the total, physical and psychosocial HRQOL domains. To determine internal consistency, Cronbach’s alpha coefficients were calculated for generic score scales.ResultsIn all, 73 survivors of BM and 36 control children participated. 18 (51%) of controls were siblings of survivors; others visited the hospital for vaccinations. The median age of children was 6 years (81 months, IQR 85 months). Survivors of BM scored significantly lower on the PedsQLTM 4.0 generic core and infant scales than control children according to parent proxy reports indicating lower HRQOL (total score 81.04 vs. 91.30, P = 0.001; physical health 87.50 vs. 100.00, P = 0.0002; psychosocial health 79.06 vs. 90.00, P = 0.001). Child self-report scores were also lower within BM survivors who were able to answer; however, the difference was not statistically significant. In total sample of survivors, the Cronbach’s alphas reached sufficient reliability of 0.70 in all three domains calculated (total score, α=0.79; physical health α= 0.77; psychosocial health α= 0.89 for child self-reports and α=0.91, α=0.91, and α=0.84 for parent proxy-reports, respectively).ConclusionThe survivors of pediatric BM endure a clearly suboptimal quality of life compared with siblings and other control children. HRQOL can be measured reliably among BM patients in developing country setting.Disclosures All authors: No reported disclosures.

Chronic Conditions and Utility-Based Health-Related Quality of Life in Adult Childhood Cancer Survivors.

Health utility, a summary measure of quality of life, has not been previously used to compare outcomes among childhood cancer survivors and individuals without a cancer history. We estimated health utility (0, death; 1, perfect health) using the Short Form-6D (SF-6D) in survivors (n = 7105) and siblings of survivors (n = 372) (using the Childhood Cancer Survivor Study cohort) and the general population (n = 12 803) (using the Medical Expenditures Panel Survey). Survivors had statistically significantly lower SF-6D scores than the general population (mean = 0.769, 95% confidence interval [CI] = 0.766 to 0.771, vs mean = 0.809, 95% CI = 0.806 to 0.813, respectively, ITALIC! P< .001, two-sided). Young adult survivors (age 18-29 years) reported scores comparable with general population estimates for people age 40 to 49 years. Among survivors, SF-6D scores were largely determined by number and severity of chronic conditions. No clinically meaningful differences were identified between siblings and the general population (mean = 0.793, 95% CI = 0.782 to 0.805, vs mean = 0.809, 95% CI = 0.806 to 0.813, respectively). This analysis illustrates the importance of chronic conditions on long-term survivor quality of life and provides encouraging results on sibling well-being. Preference-based utilities are informative tools for outcomes research in cancer survivors.

Pregnancy after chemotherapy in male and female survivors of childhood cancer treated between 1970 and 1999: a report from the Childhood Cancer Survivor Study cohort

The effect of many contemporary chemotherapeutic drugs on pregnancy and livebirth is not well established. We aimed to establish the effects of these drugs on pregnancy in male and female survivors of childhood cancer not exposed to pelvic or cranial radiotherapy. We used data from a subset of the Childhood Cancer Survivor Study cohort, which followed 5-year survivors of the most common types of childhood cancer who were diagnosed before age 21 years and treated at 27 institutions in the USA and Canada between 1970 and 1999. We extracted doses of 14 alkylating and similar DNA interstrand crosslinking drugs from medical records. We used sex-specific Cox models to establish the independent effects of each drug and the cumulative cyclophosphamide equivalent dose of all drugs in relation to pregnancies and livebirths occurring between ages 15 years and 44 years. We included siblings of survivors as a comparison group. We included 10 938 survivors and 3949 siblings. After a median follow-up of 8 years (IQR 4-12) from cohort entry or at age 15 years, whichever was later, 4149 (38%) survivors reported having or siring a pregnancy, of whom 3453 (83%) individuals reported at least one livebirth. After a median follow-up of 10 years (IQR 6-15), 2445 (62%) siblings reported having or siring a pregnancy, of whom 2201 (90%) individuals reported at least one livebirth. In multivariable analysis, survivors had a decreased likelihood of siring or having a pregnancy versus siblings (male survivors: hazard ratio [HR] 0·63, 95% CI 0·58-0·68; p<0·0001; female survivors: 0·87, 0·81-0·94; p<0·0001) or of having a livebirth (male survivors: 0·63, 0·58-0·69; p<0·0001; female survivors: 0·82, 0·76-0·89; p<0·0001). In male survivors, reduced likelihood of pregnancy was associated with upper tertile doses of cyclophosphamide (HR 0·60, 95% CI 0·51-0·71; p<0·0001), ifosfamide (0·42, 0·23-0·79; p=0·0069), procarbazine (0·30, 0·20-0·46; p<0·0001) and cisplatin (0·56, 0·39-0·82; p=0·0023). Cyclophosphamide equivalent dose in male survivors was significantly associated with a decreased likelihood of siring a pregnancy (per 5000 mg/m(2) increments: HR 0·82, 95% CI 0·79-0·86; p<0·0001). However, in female survivors, only busulfan (<450 mg/m(2) HR 0·22, 95% CI 0·06-0·79; p=0·020; ≥450 mg/m(2) 0·14, 0·03-0·55; p=0·0051) and doses of lomustine equal to or greater than 411 mg/m(2) (0·41, 0·17-0·98; p=0·046) were significantly associated with reduced pregnancy; cyclophosphamide equivalent dose was associated with risk only at the highest doses in analyses categorised by quartile (upper quartile vs no exposure: HR 0·85, 95% CI 0·74-0·98; p=0·023). Results for livebirth were similar to those for pregnancy. Greater doses of contemporary alkylating drugs and cisplatin were associated with a decreased likelihood of siring a pregnancy in male survivors of childhood cancer. However, our findings should provide reassurance to most female survivors treated with chemotherapy without radiotherapy to the pelvis or brain, given that chemotherapy-specific effects on pregnancy were generally few. Nevertheless, consideration of fertility preservation before cancer treatment remains important to maximise the reproductive potential of all adolescents newly diagnosed with cancer. National Cancer Institute, National Institutes of Health, and the American Lebanese-Syrian Associated Charities.

Adverse Obstetric Outcomes Among Early-Onset Cancer Survivors in Finland.

To evaluate risk of adverse obstetric outcomes and operative deliveries in female cancer survivors (diagnosed younger than 35 years of age) compared with female siblings of survivors. Nationwide cancer and birth registries were merged to identify 1,800 first postdiagnosis deliveries of female cancer survivors and 7,137 first deliveries of female siblings between January 1987 and December 2013. Multiple unconditional logistic regression models were used to estimate the risk for adverse obstetric outcomes and operative deliveries adjusting for maternal age, year of delivery, gestational age, and smoking. We found a significantly elevated risk for induction of labor, 19.1% in survivors and 15.6% in siblings (odds ratio [OR] 1.17, 95% confidence interval [CI] 1.02-1.35) and cesarean delivery, 23.6% in survivors and 18.6% in siblings (OR 1.15, 95% CI 1.01-1.31) among cancer survivors compared with female siblings. The risks of instrumental vaginal delivery, malpresentation, placental pathologies, and postpartum hemorrhage were not, however, elevated among cancer survivors. The highest risks of adverse obstetric outcomes were seen among women treated in their childhood (aged 0-14 years). Cancer survivors have a small but statistically increased risk for induction of labor and cesarean delivery compared with siblings without a history of cancer. Our findings indicate that pregnancies in cancer survivors are typically uncomplicated and cancer survivors should not be discouraged to have children after their cancer is cured. II.

Tobacco Use Among Siblings of Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study.

Having a brother or sister with childhood cancer may influence health behaviors during adulthood. The aim of this study was to compare tobacco use in siblings of survivors with peers and to identify factors associated with sibling tobacco use. A retrospective cohort study was conducted using adult siblings (N = 1,974) of 5+ year cancer survivors in the Childhood Cancer Survivor Study (CCSS) and participants (N = 24,105, weighted to match CCSS) in the 2007 National Health Interview Survey. Self-reported tobacco use, sociodemographic, and cancer-related risk factors were analyzed. Siblings were equally likely to have ever smoked compared to their peers (odds ratio [OR] 1.02, 95% confidence interval [CI] 0.93-1.12). Siblings were less likely to be current smokers (OR 0.83, 95%CI 0.73-0.94), but more likely to be former smokers (OR 1.21, 95%CI 1.08-1.35). Siblings with low education were more likely to ever smoke (OR 1.51, 95%CI 1.15-2.00) and be current smokers (OR 1.67, 95%CI 1.24-2.26) compared to their peers. Among siblings, risk factors for current tobacco use included the following: low income <$20,000 (OR 1.66, 95%CI 1.09-2.54), low education (OR 6.68, 95%CI 4.07-10.97), psychological distress (OR 5.36, 95%CI 2.21-13.02), and heavy alcohol use (OR 3.68, 95%CI 2.50-5.41). Siblings of survivors take up smoking at similar rates to their peers, but are more likely to quit. Efforts are needed to address disparities by providing greater psychosocial support and education for the lowest socioeconomic status families facing childhood cancer.

Factors associated with recruiting adult survivors of childhood cancer into clinic-based research.

A high proportion of pediatric cancer patients are now surviving into adulthood, but are at increased risk for late morbidity and premature mortality related to their diagnosis and therapeutic exposures. Little is known about the potential success of recruiting adult survivors of childhood cancer into research projects that would require a risk-based health evaluation within a clinical setting. Pediatric cancer survivors and siblings eligible for the current study were Childhood Cancer Survivor Study participants who lived within 100 miles of one of five Consortium for Pediatric Intervention Research institutions, regardless of where they were initially diagnosed and treated. A short survey was mailed to 829 survivors and 373 siblings to identify factors that predict interest, potential barriers, and motivators, to participation in research including a risk-based clinical evaluation. Overall, 92% of survivors responding to the survey were very interested/interested in participating in a research study requiring a visit to a local hospital clinic. Siblings of survivors were less interested than survivors in participating in such a study, with only 78% indicating that they were very interested/interested. Potential motivators to participation included visiting their treating hospital and receiving health information. The primary barrier to participation was related to taking time off from work. This study demonstrates that a subgroup of survivors would be willing to return to a long-term follow-up center to participate in intervention-based research. Identified motivating factors and perceived barriers need to be considered in determining the feasibility, design and execution of future research.

Psychological outcomes of siblings of cancer survivors: a report from the Childhood Cancer Survivor Study

To identify risk factors for adverse psychological outcomes among adult siblings of long-term survivors of childhood cancer. Cross-sectional, self-report data from 3083 adult siblings (mean age 29 years, range 18-56 years) of 5 + year survivors of childhood cancer were analyzed to assess psychological outcomes as measured by the Brief Symptom Inventory-18 (BSI-18). Sociodemographic and health data, reported by both the siblings and their matched cancer survivors, were explored as risk factors for adverse sibling psychological outcomes through multivariable logistic regression. Self-reported symptoms of psychological distress, as measured by the global severity index of the BSI-18, were reported by 3.8% of the sibling sample. Less than 1.5% of siblings reported elevated scores on two or more of the subscales of the BSI-18. Risk factors for sibling depression included having a survivor brother (OR 2.22, 95% CI 1.42-3.55), and having a survivor with impaired general health (OR 2.15, 95% CI 1.18-3.78). Siblings who were younger than the survivor reported increased global psychological distress (OR 1.81, 95% CI 1.05-3.12), as did siblings of survivors reporting global psychological distress (OR 2.32, 95% CI 1.08-4.59). Siblings of sarcoma survivors reported more somatization than did siblings of leukemia survivors (OR 2.07, 95% CI 1.05-3.98). These findings suggest that siblings of long-term childhood cancer survivors are psychologically healthy in general. There are, however, small subgroups of siblings at risk for long-term psychological impairment who may benefit from preventive risk-reduction strategies during childhood while their sibling with cancer is undergoing treatment.

Osteonecrosis in Adult Survivors of Childhood Cancer: A Report From the Childhood Cancer Survivor Study

Osteonecrosis (ON) is a potentially serious complication of therapy in survivors of childhood cancer. Our goals were to describe the incidence of ON and identify patient and treatment characteristics associated with elevated risk. The rate of self-reported ON was determined for 9,261 patients enrolled onto the Childhood Cancer Survivor Study, a cohort of 5-year survivors of childhood cancer diagnosed from 1970 to 1986, and compared with the rate in a random sample of 2,872 siblings of survivors. Survivors with positive responses were reinterviewed to confirm the diagnosis. Fifty-two cancer survivors reported ON in 78 joints, yielding 20-year cumulative incidence of 0.43% and a rate ratio (RR) of 6.2 (95% CI, 2.3 to 17.2) compared with siblings, adjusted for age and sex; 44% developed ON in a previous radiation field. The RR was greatest among survivors of stem-cell transplantation for acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), and chronic myelogenous leukemia (RR = 26.9, 66.5, and 93.1, respectively). Nontransplantation patients with ALL (RR = 6.5; 95% CI, 2.2 to 19.4), AML (RR = 11.2; 95% CI, 2.1 to 61.2), and bone sarcoma (RR = 7.3; 95% CI, 2.0 to 26.2) were at higher risk for ON. Older age at diagnosis, shorter elapsed time, older treatment era, exposure to dexamethasone (+/- prednisone), and gonadal and nongonadal radiation were independently associated with ON. ON among long-term survivors of childhood cancer is rare. However, compared with siblings, childhood cancer survivors have a significantly increased relative rate of ON, particularly those who were older at diagnosis and who received dexamethasone or radiation therapy. Future studies are needed to better delineate our findings, particularly the increased risk after gonadal radiation.

Limitations on Physical Performance and Daily Activities among Long-Term Survivors of Childhood Cancer

Survivors of childhood cancer may experience important disease- and treatment-related late effects, including functional limitations. This study evaluated performance limitations and restricted abilities to participate in personal care, to engage in routine activities like shopping or housework, and to attend work or school (participation restrictions) in a cohort of survivors of childhood cancer. Epidemiologic survey and 26 institutions that treat childhood cancer. Participants included 11 481 persons who were treated for primary brain cancer, leukemia, Hodgkin disease, non-Hodgkin lymphoma, kidney tumor, neuroblastoma, soft-tissue sarcoma, or malignant bone tumor before the age of 21 years and who survived at least 5 years after diagnosis. The comparison group included 3839 siblings of survivors of childhood cancer. Medical data were abstracted, and participants or parents (if the participants were <18 years of age at survey completion) completed a 24-page questionnaire. Compared with siblings, survivors were more likely to report performance limitations (risk ratio, 1.8 [95% CI, 1.7 to 2.0]) and to report restricted participation in personal care skills (risk ratio, 4.7 [CI, 3.0 to 7.2]), routine activities (risk ratio, 4.7 [CI, 3.6 to 6.2]), and the ability to attend work or school (risk ratio, 5.9 [CI, 4.5 to 7.6]). Survivors of brain (26.6%) and bone (36.9%) cancer were most likely to report performance limitations, restricted ability to do routine activities (20.9% and 8.5%, respectively), and restricted ability to attend work or school (20.0% and 11.2%, respectively). Survivors of brain cancer were also most likely to report restricted abilities to perform personal care (10.5%). There was the potential for participants to be healthier or more physically capable than nonparticipants or for persons to be more motivated to participate in this study if they had functional deficits. In addition, the nature of the questionnaire did not allow specific physical limitations to be measured. Long-term survivors of childhood cancer are at increased risk for functional limitations in physical performance and in participation in activities needed for daily living.

Increased Risk of Cancer among Siblings of Long-term Childhood Cancer Survivors: A Report from the Childhood Cancer Survivor Study

We determined risk of cancer among first-degree relatives of 5-year survivors of childhood leukemia, lymphoma, central nervous system tumors, sarcomas, Wilms' tumor, and neuroblastoma. Subjects were 13,703 participants in the Childhood Cancer Survivor Study. Family history was collected on 56,759 first-degree relatives using a self-reported questionnaire. Incidence was compared with age- and sex-specific rates using the U.S. Surveillance, Epidemiology and End Results program. Siblings of the survivors had an increased risk of cancer [standardized incidence ratio (SIR), 1.5; 95% confidence interval (95% CI), 1.35-1.7]. Risk was elevated for siblings of probands of leukemia (SIR, 1.3; 95% CI, 1.0-1.6), Hodgkin's disease (SIR, 1.5; 95% CI, 1.2-1.9), non-Hodgkin's lymphoma (SIR, 1.8; 95% CI, 1.3-2.5), Wilms' tumor (SIR, 1.9; 95% CI, 1.2-3.2), soft tissue sarcoma (SIR, 1.5; 95% CI, 1.0-2.2), and bone tumors (SIR, 1.6; 95% CI, 1.2-2.2). Cancer risk was elevated in siblings (SIR, 2.4; 95% CI, 1.5-3.7) and offspring (SIR, 15.0; 95% CI, 5.3-42.9) of probands with second malignant neoplasms (SMN) compared with relatives of probands without SMNs. Siblings of probands with leukemia, Hodgkin's disease, neuroblastoma, and Wilms' tumor had elevated risks for the same malignancies. Parents had no increased risk (fathers' SIR, 0.7; 95% CI, 0.7-0.8; mothers' SIR, 0.9; 95% CI, 0.9-1.0). Seventy percent of siblings' cancers developed in adulthood. These findings suggest that familial cancer syndromes may be revealed as this cohort and family members age and with accrual of more offspring and subjects with SMNs.

BOLD responses to visual stimulation in survivors of childhood cancer

Children surviving certain cancers have a high incidence of cognitive deficits caused by central nervous system (CNS) disease or treatments directed at the CNS. To establish the feasibility of using blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to study cognitive deficits in survivors of childhood cancer, we tested the hypothesis that this population has the same BOLD response to visual stimulation as healthy subjects. We used BOLD fMRI to measure spatial and temporal patterns of brain activity after brief visual stimulation in 16 survivors of childhood cancer, 11 age-similar healthy siblings of survivors, and 16 healthy adults. Functional data for the survivors were analyzed with two general linear models, one used a canonical hemodynamic response function (HRF) and the other used a Fourier set as basis functions. The measured BOLD signal and brain activation patterns were similar in the survivors with both models. The BOLD signal for survivors was qualitatively similar in timing and shape, but there were significant quantitative differences as compared with healthy subjects. The activation was normally located in the primary visual cortex in 13 survivors, but the activation volume was significantly smaller in brain tumor survivors than in other groups. These findings demonstrate the feasibility of using BOLD fMRI to investigate brain function in survivors of childhood cancer. However, fMRI studies in this population must take into account effects of quantitative differences in their BOLD responses as compared to healthy subjects.