Treatment Responses in Patients With Psoriatic Arthritis Axial Disease According to Human Leukocyte Antigen-B27 Status: An Analysis From the CorEvitas Psoriatic Arthritis/Spondyloarthritis Registry.

OBJECTIVE: Axial disease is common and burdensome in patients with psoriatic arthritis (PsA). Human leukocyte antigen-B27 (HLA-B27) is a risk factor for axial PsA; treatment response by HLA-B27 status is inadequately characterized. This study evaluated responses to biologic disease-modifying antirheumatic drugs (bDMARDs) or targeted synthetic DMARDs (tsDMARDs) overall and by HLA-B27 status in patients with PsA axial disease. METHODS: This observational study included participants in the CorEvitas (formerly Corrona) PsA/Spondyloarthritis Registry who initiated bDMARD or tsDMARD treatment at baseline, had a 6-month follow-up visit, fulfilled Classification Criteria for Psoriatic Arthritis, had a baseline Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score of ≥4, and had known HLA-B27 status. Disease characteristics at baseline and 6 months were evaluated overall and by HLA-B27 status. Association between HLA-B27 status and treatment response was evaluated using an analysis of covariance model. RESULTS: The analysis included 173 bDMARD or tsDMARD treatment initiations (54 [31.2%] among patients with HLA-B27+ status and 119 [68.8%] among patients with HLA-B27- status). BASDAI total and component scores decreased by ≤0.84 across groups after 6 months of bDMARD or tsDMARD therapy; these changes are not considered clinically meaningful. HLA-B27 status was not statistically significantly associated with changes in axial-related outcomes. CONCLUSION: In patients with PsA axial disease, 6 months of bDMARD or tsDMARD therapy provided only mild improvements in axial-related outcomes, irrespective of HLA-B27 status. This continued high disease activity reflects a critical unmet need for focus on the axial domain of PsA and for additional safe and effective therapies for psoriatic axial disease.

Three-dimensional ultrasound is a reliable alternative in endovascular aortic repair surveillance.

OBJECTIVE: Three-dimensional ultrasound (3D-US) has already demonstrated improved reproducibility with a high degree of agreement (intermodality variability), reproducibility (interoperator variability), and repeatability (intraoperator variability) compared with conventional two-dimensional ultrasound (2D-US) when estimating the maximum diameter of native abdominal aortic aneurysms (AAAs). The aim of the present study was, in a clinical, multicenter setting, to evaluate the accuracy of 3D-US with aneurysm model quantification software (3D-US abdominal aortic aneurysm [AAA] model) for endovascular aortic aneurysm repair (EVAR) sac diameter assessment vs that of computed tomography angiography (CTA) and 2D-US. METHODS: A total of 182 patients who had undergone EVAR from April 2016 to December 2017 and were compliant with a standardized EVAR surveillance program were enrolled from five different vascular centers (Rigshospitalet, Copenhagen, Denmark; Catharina Ziekenhuis, Eindhoven, Netherlands; L'hospital de la Timone, Paris, France; Cleveland Clinic, Cleveland, Ohio; and The Christ Hospital, Cincinnati, Ohio) in four countries. All image acquisitions were performed at the local sites (ie, 2D-US, 3D-US, CTA). Only the 2D-US and CTA readings were performed both locally and centrally. All images were read centrally by the US and CTA core laboratory. Anonymized image data were read in a randomized and blinded manner. RESULTS: The sample used to estimate the accuracy of the 3D-US AAA model and 2D-US included 164 patients and 177 patients, respectively. The Bland-Altman analysis revealed that the mean difference between CTA and 3D-US was -2.43 mm (95% confidence interval [CI], -5.20 to 0.14; P = .07) with a lower and upper limit of agreement of -8.9 mm (95% CI, -9.3 to -8.4) and 2.7 mm (95% CI, 2.3-3.2), respectively. For 2D-US and CTA, the mean difference was -3.62 mm (95% CI, -6.14 to -1.10; P = .002), with a lower and upper limit of agreement of -10.3 mm (95% CI, -10.8 to -9.8) and 2.5 mm (95% CI, 2-2.9), respectively. CONCLUSIONS: The 3D-US AAA model showed no significant difference compared with CTA for measuring the anteroposterior diameter, indicating less bias for 3D-US compared with 2D-US. Thus, 3D-US with AAA model software is a viable modality for anteroposterior diameter assessment for surveillance after EVAR.

Health-related Quality of Life (HR-QOL) and Chronic Health Conditions in Survivors of Childhood Acute Myeloid Leukemia (AML) with Down Syndrome (DS): A Report From the Children's Oncology Group.

Survival rates for children with Down syndrome (DS) and acute myeloid leukemia (AML) are high; however, little is known regarding the health-related quality of life (HR-QOL) of these survivors. Individuals who survived ≥5 years following diagnosis of childhood AML were invited to complete parent or patient-report surveys measuring HR-QOL and chronic health conditions. In total, 26 individuals with DS had a median age at diagnosis of 1.8 years (range, 0.77 to 10.9 y) and median age at interview of 15 years (range, 8.3 to 27.6 y). Participants with DS and AML were compared with AML survivors without DS whose caregiver completed a HR-QOL survey (CHQ-PF50). In total, 77% of survivors with DS reported ≥1 chronic health condition compared with 50% of AML survivors without DS (P=0.07). Mean physical and psychosocial QOL scores for children with DS and AML were statistically lower than the population mean, though not discrepant from AML survivors without DS. Although the overall prevalence of chronic health conditions in survivors with DS is higher than in survivors without DS, prior studies of children with DS have reported similarly high rates of chronic health conditions, suggesting that AML therapy may not substantially increase this risk.

Performance comparison of Illumina and ion torrent next-generation sequencing platforms for 16S rRNA-based bacterial community profiling.

High-throughput sequencing of the taxonomically informative 16S rRNA gene provides a powerful approach for exploring microbial diversity. Here we compare the performances of two common "benchtop" sequencing platforms, Illumina MiSeq and Ion Torrent Personal Genome Machine (PGM), for bacterial community profiling by 16S rRNA (V1-V2) amplicon sequencing. We benchmarked performance by using a 20-organism mock bacterial community and a collection of primary human specimens. We observed comparatively higher error rates with the Ion Torrent platform and report a pattern of premature sequence truncation specific to semiconductor sequencing. Read truncation was dependent on both the directionality of sequencing and the target species, resulting in organism-specific biases in community profiles. We found that these sequencing artifacts could be minimized by using bidirectional amplicon sequencing and an optimized flow order on the Ion Torrent platform. Results of bacterial community profiling performed on the mock community and a collection of 18 human-derived microbiological specimens were generally in good agreement for both platforms; however, in some cases, results differed significantly. Disparities could be attributed to the failure to generate full-length reads for particular organisms on the Ion Torrent platform, organism-dependent differences in sequence error rates affecting classification of certain species, or some combination of these factors. This study demonstrates the potential for differential bias in bacterial community profiles resulting from the choice of sequencing platform alone.

Psychosexual functioning among adult female survivors of childhood cancer: a report from the childhood cancer survivor study.

PURPOSE: Childhood cancer survivors may be at risk for impaired psychosexual functioning as a direct result of their cancer or its treatments, psychosocial difficulties, and/or diminished quality of life. PATIENTS AND METHODS: Two thousand one hundred seventy-eight female adult survivors of childhood cancer and 408 female siblings from the Childhood Cancer Survivor Study (CCSS) completed a self-report questionnaire about their psychosexual functioning and quality of life. On average, participants were age 29 years (range, 18 to 51 years) at the time of the survey, had been diagnosed with cancer at a median age of 8.5 years (range, 0 to 20) and were most commonly diagnosed with leukemia (33.2%) and Hodgkin lymphoma (15.4%). RESULTS: Multivariable analyses suggested that after controlling for sociodemographic differences, survivors reported significantly lower sexual functioning (mean difference [MnD], -0.2; P = .01), lower sexual interest (MnD, -0.2; P < .01), lower sexual desire (MnD, -0.3; P < .01), lower sexual arousal (MnD, -0.3; P < .01), lower sexual satisfaction (MnD, -0.2; P = .01), and lower sexual activity (MnD, -0.1; P = .02) compared with siblings. Risk factors for poorer psychosexual functioning among survivors included older age at assessment, ovarian failure at a younger age, treatment with cranial radiation, and cancer diagnosis during adolescence. CONCLUSION: Decreased sexual functioning among female survivors of childhood cancers seems to be unrelated to emotional factors and is likely to be an underaddressed issue. Several risk factors among survivors have been identified that assist in defining high-risk subgroups who may benefit from targeted screening and interventions.

Relations between posttraumatic stress and posttraumatic growth in long-term survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

OBJECTIVE: Contemporary models of trauma suggest that posttraumatic stress and growth should be related and that symptoms of stress resulting from a perceived trauma (e.g., childhood cancer) are prerequisite for posttraumatic growth (PTG) to occur. However, empirical data regarding the relationship of posttraumatic stress and growth have been equivocal. The purpose of this study is to examine the relationship between posttraumatic stress symptoms (PTSS) and PTG among adult survivors of childhood cancer. METHODS: Survey methods were used to collect data from 6,162 survivors participating in the Childhood Cancer Survivor Study (CCSS). Nonparametric correlation was examined pairwise between PTG and PTSS using Spearman's correlation coefficient with 95% confidence intervals, with nonlinear canonical correlation analysis being conducted to examine relationships between subscales. A multivariable partial proportional odds model was also fit for PTG total quartiles focusing on associations with PTSS total quartiles while adjusting for sociodemographic and medical variables. RESULTS: Examination of unadjusted PTSS and PTG total scores revealed a Spearman correlation of 0.11 (p < .001), with coefficients ranging from 0.03 to 0.17 between total and subscale scores. The nonlinear canonical correlation analyses resulted in two dimensions with eigenvalues of 0.15 and 0.14, resulting in a fit value of 0.30 and evidence that little variability in the data (15%) was explained by the weighted combinations of the variables. CONCLUSIONS: Although statistically significant, these results do not indicate a robust relationship between PTSS and PTG among adult survivors of childhood cancer. Theories suggesting that PTSS is a prerequisite for PTG should be reconsidered.

Aging and risk of severe, disabling, life-threatening, and fatal events in the childhood cancer survivor study.

PURPOSE: The first generation of childhood cancer survivors is now aging into their fourth and fifth decades of life, yet health risks across the aging spectrum are not well established. METHODS: Analyses included 14,359 5-year survivors from the Childhood Cancer Survivor Study, who were first diagnosed when they were younger than 21 years old and who received follow-up for a median of 24.5 years after diagnosis (range, 5.0 to 39.3 years) along with 4,301 of their siblings. Among the survivors, 5,604 were at least 35 years old (range, 35 to 62 years) at last follow-up. Severe, disabling, life-threatening, and fatal health conditions more than 5 years from diagnosis were classified using the Common Terminology Criteria for Adverse Events, grades 3 to 5 (National Cancer Institute). RESULTS: The cumulative incidence of a severe, disabling, life-threatening, or fatal health condition was greater among survivors than siblings (53.6%; 95% CI, 51.5 to 55.6; v 19.8%; 95% CI, 17.0 to 22.7) by age 50 years. When comparing survivors with siblings, hazard ratios (HR) were significantly increased within the age group of 5 to 19 years (HR, 6.8; 95% CI, 5.5 to 8.3), age group of 20 to 34 years (HR, 3.8; 95% CI, 3.2 to 4.5), and the ≥ 35 years group (HR, 5.0; 95% CI, 4.1 to 6.1), with the HR significantly higher among those ≥ 35 years versus those 20 to 34 years old (P = .03). Among survivors who reached age 35 years without a previous grade 3 or 4 condition, 25.9% experienced a subsequent grade 3 to 5 condition within 10 years, compared with 6.0% of siblings (P < .001). CONCLUSION: Elevated risk for morbidity and mortality among survivors increases further beyond the fourth decade of life, which affects the future clinical demands of this population relative to ongoing surveillance and interventions.

Health conditions and quality of life in survivors of childhood acute myeloid leukemia comparing post remission chemotherapy to BMT: a report from the children's oncology group.

BACKGROUND: Therapy for childhood acute myeloid leukemia (AML) has historically included chemotherapy with or without autologous bone marrow transplant (autoBMT) or allogeneic hematopoietic stem cell transplantation (alloBMT). We sought to compare health-related quality-of-life (HRQOL) outcomes between these treatment groups. PROCEDURE: Five-year survivors of AML diagnosed before age 21 and enrolled and treated from 1979 to 1995 on one of 4 national protocols were interviewed. These survivors or proxy caregivers completed a health questionnaire and an HRQOL measure. RESULTS: Of 180 survivors, 100 were treated with chemotherapy only, 26 with chemotherapy followed by autoBMT, and 54 with chemotherapy followed by alloBMT. Median age at interview was 20 years (range 8-39). Twenty-one percent reported a severe or life-threatening chronic health condition (chemotherapy-only 16% vs. autoBMT 21% vs. alloBMT 33%; P = 0.02 for chemotherapy-only vs. alloBMT). Nearly all (95%) reported excellent, very good or good health. Reports of cancer-related pain and anxiety did not vary between groups. HRQOL scores among 136 participants ≥14 years of age were similar among groups and to the normative population, though alloBMT survivors had a lower physical mean summary score (49.1 alloBMT vs. 52.2 chemotherapy-only; P = 0.03). Multivariate analyses showed the presence of severe chronic health conditions to be a strong predictor of physical but not mental mean summary scores. CONCLUSIONS: Overall HRQOL scores were similar among treatment groups, although survivors reporting more health conditions or cancer-related pain had diminished HRQOL. Attention to chronic health conditions and management of cancer-related pain may improve QOL.

Modifiable risk factors and major cardiac events among adult survivors of childhood cancer.

PURPOSE: To evaluate the relative contribution of modifiable cardiovascular risk factors on the development of major cardiac events in aging adult survivors of childhood cancer. PATIENTS AND METHODS: Among 10,724 5-year survivors (median age, 33.7 years) and 3,159 siblings in the Childhood Cancer Survivor Study, the prevalence of hypertension, diabetes mellitus, dyslipidemia, and obesity was determined, along with the incidence and severity of major cardiac events such as coronary artery disease, heart failure, valvular disease, and arrhythmia. On longitudinal follow-up, rate ratios (RRs) of subsequent cardiac events associated with cardiovascular risk factors and cardiotoxic therapy were assessed in multivariable Poisson regression models. RESULTS: Among survivors, the cumulative incidence of coronary artery disease, heart failure, valvular disease, and arrhythmia by 45 years of age was 5.3%, 4.8%, 1.5%, and 1.3%, respectively. Two or more cardiovascular risk factors were reported by 10.3% of survivors and 7.9% of siblings. The risk for each cardiac event increased with increasing number of cardiovascular risk factors (all P(trend) < .001). Hypertension significantly increased risk for coronary artery disease (RR, 6.1), heart failure (RR, 19.4), valvular disease (RR, 13.6), and arrhythmia (RR, 6.0; all P values < .01). The combined effect of chest-directed radiotherapy plus hypertension resulted in potentiation of risk for each of the major cardiac events beyond that anticipated on the basis of an additive expectation. Hypertension was independently associated with risk of cardiac death (RR, 5.6; 95% CI, 3.2 to 9.7). CONCLUSION: Modifiable cardiovascular risk factors, particularly hypertension, potentiate therapy-associated risk for major cardiac events in this population and should be the focus of future interventional studies.

Predictors of risk-based medical follow-up: a report from the Childhood Cancer Survivor Study.

PURPOSE: The purpose of this study is to conduct an intervention study designed to assess the effectiveness of using a newsletter to increase medical follow-up in pediatric cancer survivors at risk of selected treatment complications. METHODS: Survivors participating in the Childhood Cancer Survivor Study who were at least 25 years of age and at risk of cardiovascular disease, breast cancer, or osteoporosis related to previous cancer treatment were randomly assigned to receive a newsletter featuring brief health risk information or a newsletter including an insert providing more comprehensive health risk information. A follow-up survey distributed 24 months after the newsletter intervention assessed predictors of medical follow-up. RESULTS: Overall, there were no differences found among the groups in terms of access to a treatment summary, medical follow-up, discussion of childhood cancer health risks, and medical screening for the targeted health behaviors. One exception, indicating borderline significance was that women at risk for osteoporosis who received the newsletter insert were more likely to have discussed their risk with a doctor than those who only received the brief information (10.1 % vs. 4.0 % p = 0.05). Discussion of breast cancer (OR = 2.15; 95 % CI = 1.74-2.66), heart disease (OR = 5.54; 95 % CI = 4.67-6.57) and osteoporosis (OR = 10.6; 95 % CI = 8.34-13.47) risk with physician significantly predicted report of undergoing screening for targeted behavior in previous 2 years as did physician access to treatment summary. CONCLUSIONS: More detailed content in a newsletter had minimal effect on recommended screening. However, survivor's discussion of cancer-related risks with one's doctor significantly influenced participation in health screening. These results highlight the integral role of communication in health behavior. IMPLICATIONS FOR CANCER SURVIVORS: This study is designed to assess communication strategies that increase medical follow-up in pediatric cancer survivors at risk of selected treatment complications. The results are of great importance not only to the pediatric oncology community but also the broad range of adult oncology medical specialties who are directly involved in the long-term medical care of this ever increasing population of cancer survivors.

Two-stage model-free tests of synergy in drug combinations.

Laska et al. ( 1994 ) proposed a model-free method of detecting synergy in two drug combinations that requires no assumptions about the underlying dose-response curves of the drugs, just an estimate of the potency ratio of the two drugs. It was noted that the power of this method is highly dependent on the accuracy of the potency ratio estimated, with low power when the estimate is inaccurate. Additionally, the test used to detect synergy (the Min test) has been shown to be conservative in many practical applications, and non-monotonic alternative tests that have greater power have been proposed. We suggest a two-stage, non-monotonic alternative to the Laska et al. model-free test that is less dependent on the accuracy of potency ratio estimate and has greater power in many situations. We illustrate the method with an example of two chemotherapeutic agents.

Pain in long-term adult survivors of childhood cancers and their siblings: a report from the Childhood Cancer Survivor Study.

Little is known about pain among long-term adult survivors of childhood cancers. The study investigated pain prevalence in this population compared with sibling controls and examined pain-related risk factors. Three self-reported pain outcomes including pain conditions, prescription analgesics used, and pain attributed to cancer and treatment were assessed among 10,397 cancer survivors and 3034 sibling controls from the Childhood Cancer Survivor Study. Pain conditions (pain/abnormal sensation, migraines, and other headaches) were reported by 12.3%, 15.5%, and 20.5% of survivors, respectively; 16.7% of survivors reported use of prescription analgesics, and 21% attributed pain to cancer and treatment. Risks of reporting pain conditions and using prescription analgesics were higher among survivors than siblings, adjusting for sociodemographic factors. Younger age at diagnosis and a history of non-Hodgkin lymphoma, Wilms tumor, or neuroblastoma (compared to leukemia) were associated with greater risk of reporting pain conditions. A history of bone cancer or soft tissue sarcoma (compared to leukemia) was associated with greater risks of using prescription analgesics and cancer-related pain attribution. Non-brain-directed scatter irradiation was associated with elevated risk for migraines and cancer-related pain attribution. Female gender and lower educational attainment were associated with increased reports of all 3 pain outcomes; minority status, unemployment, and being single were associated with greater risks for reporting pain conditions. These findings contribute to the understanding of pain and associated risk factors among adult survivors of childhood cancer and suggest areas of focus for pain intervention.

Long-term health-related outcomes in survivors of childhood cancer treated with HSCT versus conventional therapy: a report from the Bone Marrow Transplant Survivor Study (BMTSS) and Childhood Cancer Survivor Study (CCSS).

HSCT is being increasingly offered as a curative option for children with hematologic malignancies. Although survival has improved, the long-term morbidity ascribed to the HSCT procedure is not known. We compared the risk of chronic health conditions and adverse health among children with cancer treated with HSCT with survivors treated conventionally, as well as with sibling controls. HSCT survivors were drawn from BMTSS (N = 145), whereas conventionally treated survivors (N = 7207) and siblings (N = 4020) were drawn from CCSS. Self-reported chronic conditions were graded with CTCAEv3.0. Fifty-nine percent of HSCT survivors reported ≥ 2 conditions, and 25.5% reported severe/life-threatening conditions. HSCT survivors were more likely than sibling controls to have severe/life-threatening (relative risk [RR] = 8.1, P < .01) and 2 or more (RR = 5.7, P < .01) conditions, as well as functional impairment (RR = 7.7, P < .01) and activity limitation (RR = 6.3, P < .01). More importantly, compared with CCSS survivors, BMTSS survivors demonstrated significantly elevated risks (severe/life-threatening conditions: RR = 3.9, P < .01; multiple conditions: RR = 2.6, P < .01; functional impairment: RR = 3.5, P < .01; activity limitation: RR = 5.8, P < .01). Unrelated donor HSCT recipients were at greatest risk. Childhood HSCT survivors carry a significantly greater burden of morbidity not only compared with noncancer populations but also compared with conventionally treated cancer patients, providing evidence for close monitoring of this high-risk population.

Decreased fertility among female childhood cancer survivors who received 22-27 Gy hypothalamic/pituitary irradiation: a report from the Childhood Cancer Survivor Study.

OBJECTIVE: To evaluate the effect of hypothalamic/pituitary radiation (HPT RT) dose on the occurrence of first pregnancy. DESIGN: Retrospective cohort study of childhood cancer 5-year survivors (CCS) diagnosed between 1970 and 1986 before 21 years of age at one of 26 North American pediatric cancer treatment centers. SETTING: Self-administered questionnaire. PATIENT(S): A total of 3,619 female CCS who participated in the Childhood Cancer Survivor Study and received no or scatter (≤0.1 Gy) radiation to the ovaries and 2,081 female siblings (Sibs) of the participants. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): Self-reported pregnancy events. RESULT(S): As a group, CCS were as likely to report being pregnant as Sibs (hazard ratio 1.07, 95% confidence interval 0.97-1.19). Multivariable models showed a significant decrease in the risk of pregnancy with HPT RT doses≥22 Gy compared with those CCS receiving no HPT RT. CONCLUSION(S): These results support the hypothesis that exposures of 22-27 Gy HPT RT may be a contributing factor to infertility among female CCS.

Auditory complications in childhood cancer survivors: a report from the childhood cancer survivor study.

BACKGROUND: Studies have found associations between cancer therapies and auditory complications, but data are limited on long-term outcomes and risks associated with multiple exposures. PROCEDURE: The Childhood Cancer Survivor Study is a retrospective cohort investigating health outcomes of long-term survivors (5+ years) diagnosed and treated between 1970 and 1986 compared to a randomly selected sibling cohort. Questionnaires were completed by 14,358 survivors of childhood cancer and 4,023 sibling controls. Analysis determined the first occurrence of four auditory conditions in two time periods: diagnosis to 5 years post-diagnosis, and ≥ 5 years post-diagnosis. Multivariable analyses determined the relative risks (RR) and 95% confidence interval (CI) of auditory conditions by treatment exposure. RESULTS: Five or more years from cancer diagnosis, survivors were at increased risk of problems hearing sounds (RR = 2.3; 95% CI: 1.8-2.8), tinnitus (RR = 1.7; 95% CI: 1.4-2.1), hearing loss requiring an aid (RR = 4.4; 95% CI: 2.8-6.9), and hearing loss in 1 or both ears not corrected by a hearing aid (RR = 5.2; 95% CI: 2.8-9.5), when compared to siblings. Temporal lobe and posterior fossa radiation was associated with these outcomes in a dose-dependent fashion. Exposure to platinum compounds was associated with an increased risk of problems hearing sounds (RR = 2.1; 95% CI: 1.3-3.2), tinnitus (RR = 2.8; 95% CI: 1.9-4.2), and hearing loss requiring an aid (RR = 4.1; 95% CI: 2.5-6.7). CONCLUSIONS: Childhood cancer survivors are at risk of developing auditory complications. Radiation and platinum compounds are determinants of this risk. Follow-up is needed to evaluate the impact of auditory conditions on quality of life.

Prevalence and predictors of chronic health conditions after hematopoietic cell transplantation: a report from the Bone Marrow Transplant Survivor Study.

Long-term survival is now an expected outcome after hematopoietic cell transplantation (HCT). However, the burden of morbidity long-term after HCT remains unknown. We examined the magnitude of risk of chronic health conditions reported by 1022 HCT survivors and their siblings (n = 309). A severity score (grades 1 [mild] through 4 [life-threatening]) was assigned to each health condition using the Common Terminology Criteria for Adverse Events, Version 3. Sixty-six percent of the HCT survivors reported at least one chronic condition; 18% reported severe/life-threatening conditions; comparable values in siblings were 39% and 8%, respectively (P < .001). The cumulative incidence of a chronic health condition among HCT survivors was 59% (95% confidence interval [CI], 56%-62%) at 10 years after HCT; for severe/life-threatening conditions or death from chronic health conditions, the 10-year cumulative incidence approached 35% (95% CI, 32%-39%). HCT survivors were twice as likely as siblings to develop a chronic condition (95% CI, 1.6-2.1), and 3.5 times to develop severe/life-threatening conditions (95% CI, 2.3-5.4). HCT survivors with chronic graft-versus-host disease were 4.7 times as likely to develop severe/life-threatening conditions (95% CI, 3.0-7.2). The burden of long-term morbidity borne by HCT survivors is substantial, and long-term follow-up of patients who received transplantation is recommended.

Fertility of male survivors of childhood cancer: a report from the Childhood Cancer Survivor Study.

PURPOSE: This study was undertaken to determine the effect of treatment for childhood cancer on male fertility. PATIENTS AND METHODS: We reviewed the fertility of male Childhood Cancer Survivor Study survivor and sibling cohorts who completed a questionnaire. We abstracted the chemotherapeutic agents administered, the cumulative dose of drug administered for selected drugs, and the doses and volumes of all radiation therapy from medical records. Risk factors for siring a pregnancy were evaluated using Cox proportional hazards models. RESULTS: The 6,224 survivors age 15 to 44 years who were not surgically sterile were less likely to sire a pregnancy than siblings (hazard ratio [HR], 0.56; 95% CI, -0.49 to 0.63). Among survivors, the HR of siring a pregnancy was decreased by radiation therapy of more than 7.5 Gy to the testes (HR, 0.12; 95% CI, -0.02 to 0.64), higher cumulative alkylating agent dose (AAD) score or treatment with cyclophosphamide (third tertile HR, 0.42; 95% CI, -0.31 to 0.57) or procarbazine (second tertile HR, 0.48; 95% CI, -0.26 to 0.87; third tertile HR, 0.17; 95% CI, -0.07 to 0.41). Compared with siblings, the HR for ever siring a pregnancy for survivors who had an AAD score = 0, a hypothalamic/pituitary radiation dose = 0 Gy, and a testes radiation dose = 0 Gy was 0.91 (95% CI, 0.73 to 1.14; P = .41). CONCLUSION: This large study identified risk factors for decreased fertility that may be used for counseling male cancer patients.

Ocular late effects in childhood and adolescent cancer survivors: a report from the childhood cancer survivor study.

INTRODUCTION: Approximately 80% of children currently survive 5 years following diagnosis of their cancer. Studies based on limited data have implicated certain cancer therapies in the development of ocular sequelae in these survivors. PROCEDURE: The Childhood Cancer Survivor Study (CCSS) is a retrospective cohort study investigating health outcomes of 5+ year survivors diagnosed and treated between 1970 and 1986 compared to a sibling cohort. The baseline questionnaire included questions about the first occurrence of six ocular conditions. Relative risks (RR) and 95% confidence intervals (CI) were calculated from responses of 14,362 survivors and 3,901 siblings. RESULTS: Five or more years from the diagnosis, survivors were at increased risk of cataracts (RR: 10.8; 95% CI: 6.2-18.9), glaucoma (RR: 2.5; 95% CI: 1.1-5.7), legal blindness (RR: 2.6; 95% CI: 1.7-4.0), double vision (RR: 4.1; 95% CI: 2.7-6.1), and dry eyes (RR: 1.9; 95% CI: 1.6-2.4), when compared to siblings. Dose of radiation to the eye was significantly associated with risk of cataracts, legal blindness, double vision, and dry eyes, in a dose-dependent manner. Risk of cataracts were also associated with radiation 3,000+ cGy to the posterior fossa (RR: 8.4; 95% CI: 5.0-14.3), temporal lobe (RR: 9.4; 95% CI: 5.6-15.6), and exposure to prednisone (RR: 2.3; 95% CI: 1.6-3.4). CONCLUSIONS: Childhood cancer survivors are at risk of developing late occurring ocular complications, with exposure to glucocorticoids and cranial radiation being important determinants of increased risk. Long-term follow-up is needed to evaluate potential progression of ocular deficits and impact on quality of life.

Cardiac outcomes in a cohort of adult survivors of childhood and adolescent cancer: retrospective analysis of the Childhood Cancer Survivor Study cohort.

OBJECTIVES: To assess the incidence of and risks for congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities among adult survivors of childhood and adolescent cancers. DESIGN: Retrospective cohort study. SETTING: 26 institutions that participated in the Childhood Cancer Survivor Study. PARTICIPANTS: 14,358 five year survivors of cancer diagnosed under the age of 21 with leukaemia, brain cancer, Hodgkin's lymphoma, non-Hodgkin's lymphoma, kidney cancer, neuroblastoma, soft tissue sarcoma, or bone cancer between 1970 and 1986. Comparison group included 3899 siblings of cancer survivors. MAIN OUTCOME MEASURES: Participants or their parents (in participants aged less than 18 years) completed a questionnaire collecting information on demographic characteristics, height, weight, health habits, medical conditions, and surgical procedures occurring since diagnosis. The main outcome measures were the incidence of and risk factors for congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities in survivors of cancer compared with siblings. RESULTS: Survivors of cancer were significantly more likely than siblings to report congestive heart failure (hazard ratio (HR) 5.9, 95% confidence interval 3.4 to 9.6; P<0.001), myocardial infarction (HR 5.0, 95% CI 2.3 to 10.4; P<0.001), pericardial disease (HR 6.3, 95% CI 3.3 to 11.9; P<0.001), or valvular abnormalities (HR 4.8, 95% CI 3.0 to 7.6; P<0.001). Exposure to 250 mg/m(2) or more of anthracyclines increased the relative hazard of congestive heart failure, pericardial disease, and valvular abnormalities by two to five times compared with survivors who had not been exposed to anthracyclines. Cardiac radiation exposure of 1500 centigray or more increased the relative hazard of congestive heart failure, myocardial infarction, pericardial disease, and valvular abnormalities by twofold to sixfold compared to non-irradiated survivors. The cumulative incidence of adverse cardiac outcomes in cancer survivors continued to increase up to 30 years after diagnosis. CONCLUSION: Survivors of childhood and adolescent cancer are at substantial risk for cardiovascular disease. Healthcare professionals must be aware of these risks when caring for this growing population.