Publications by authors named "David R Doody"

66 Publications

Late health outcomes after dexrazoxane treatment: A report from the Children's Oncology Group.

Cancer 2021 Oct 13. Epub 2021 Oct 13.

Oishei Children's Hospital, Roswell Park Comprehensive Center, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, Buffalo, New York.

Background: The objective of this study was to examine long-term outcomes among children newly diagnosed with cancer who were treated in dexrazoxane-containing clinical trials.

Methods: P9404 (acute lymphoblastic leukemia/lymphoma [ALL]), P9425 and P9426 (Hodgkin lymphoma), P9754 (osteosarcoma), and Dana-Farber Cancer Institute 95-01 (ALL) enrolled 1308 patients between 1996 and 2001: 1066 were randomized (1:1) to doxorubicin with or without dexrazoxane, and 242 (from P9754) were nonrandomly assigned to receive dexrazoxane. Trial data were linked with the National Death Index, the Organ Procurement and Transplantation Network, the Pediatric Health Information System (PHIS), and Medicaid. Osteosarcoma survivors from the Childhood Cancer Survivor Study (CCSS; n = 495; no dexrazoxane) served as comparators in subanalyses. Follow-up events were assessed with cumulative incidence, Cox regression, and Fine-Gray methods.

Results: In randomized trials (cumulative prescribed doxorubicin dose, 100-360 mg/m ; median follow-up, 18.6 years), dexrazoxane was not associated with relapse (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.63-1.13), second cancers (HR, 1.19; 95% CI, 0.62-2.30), all-cause mortality (HR, 1.07; 95% CI, 0.78-1.47), or cardiovascular mortality (HR, 1.45; 95% CI, 0.41-5.16). Among P9754 patients (all exposed to dexrazoxane; cumulative doxorubicin, 450-600 mg/m ; median follow-up, 16.6-18.4 years), no cardiovascular deaths or heart transplantation occurred. The 20-year heart transplantation rate among CCSS osteosarcoma survivors (mean doxorubicin, 377 ± 145 mg/m ) was 1.6% (vs 0% in P9754; P = .13). Among randomized patients, serious cardiovascular outcomes (cardiomyopathy, ischemic heart disease, and stroke) ascertained by PHIS/Medicaid occurred less commonly with dexrazoxane (5.6%) than without it (17.6%; P = .02), although cardiomyopathy rates alone did not differ (4.4% vs 8.1%; P = .35).

Conclusions: Dexrazoxane did not appear to adversely affect long-term mortality, event-free survival, or second cancer risk.
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http://dx.doi.org/10.1002/cncr.33974DOI Listing
October 2021

Time and geographic variations in human papillomavirus vaccine uptake in Washington state.

Prev Med 2021 Jul 31;153:106753. Epub 2021 Jul 31.

Epidemiology Program, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA, United States of America. Electronic address:

This study examines geographic variations of human papillomavirus (HPV) vaccine uptake, the most significant disparity in HPV vaccination, in Washington State. We evaluated Washington State Immunization Information System (WA-IIS) data on target age (11-12 year old adolescents) between 2008 and 2018. A Bayesian spatio-temporal analysis was conducted to examine uptake at the census tract level. Urban-rural disparities in vaccine rates were assessed using t-tests. Persistently high and low vaccine areas and their contributing sociodemographic factors were then identified using a multinomial logistic regression. HPV vaccine uptake gradually increased after 2010, but remained persistently low. Average vaccine uptake rates from 2010 through 2018 in urban areas were 11%-34% for initiation and 4-19% for completion. These rates were 9-22% initiation and 3-11% completion in rural areas. We observed statistically significant (p < 0.05) differences between the estimated vaccine rates for urban and rural census tracts. Race/ethnicity and socioeconomic status were associated with this urban-rural disparity. The odds of being in low vaccine rural areas increased with increase in Area Deprivation Index (ADI) (OR = 1.14, CI = (1.10, 1.19)), and decreased with percentage increase in Black (OR = 0.43, CI = (0.02, 0.85)) and Hispanic (OR = 0.97, CI = (0.94, 1.00)) population. Bayesian spatial analysis was effective in capturing spatio-temporal patterns in HPV vaccine rates and identifying areas with persistently low vaccination over time. This analytic approach can be used to guide public health policies and geographically target interventions to reduce HPV vaccine disparities and to prevent future HPV-related cancers.
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http://dx.doi.org/10.1016/j.ypmed.2021.106753DOI Listing
July 2021

Hospitalization and mortality outcomes in the first 5 years after a childhood cancer diagnosis: a population-based study.

Cancer Causes Control 2021 Jul 9;32(7):739-752. Epub 2021 Apr 9.

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Purpose: Children with cancer are frequently hospitalized. However, hospitalization and death by disease category are not well defined < 5 years from diagnosis.

Methods: We conducted a retrospective cohort study using linked cancer registry-hospital discharge-vital records to identify cancer cases < 20 years at diagnosis during 1987-2012 (n = 4,567) and comparison children without cancer, matched on birth year and sex (n = 45,582). Data linkage identified serious morbidities resulting in cancer- and non-cancer-related hospitalizations or deaths < 5 years from diagnosis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated to compare relative hospitalization and mortality by disease category and after excluding cancer-related outcomes. Among cancer cases, relative risks of these outcomes for children with solid tumors compared with children with leukemia/lymphoma were also estimated.

Results: Greater rates of all-cause hospitalization (281.5/1,000 vs. 6.2/1,000 person years) and death (40.7/1,000 vs. 0.15/1,000 person years) were observed in childhood cancer cases than comparators and across all diagnosis categories. Increased hospitalization (31.0/1,000 vs. 6.2/1,000 person years; HR 5.0, 95% CI 4.5-5.5) and death (1.0/1,000 vs. 0.15/1,000 person years; HR 10.4, 95% CI 5.6-19.1) rates remained when cancer-related outcomes were excluded. Although HRs for hospitalization and death did not differ greatly by treatment era, absolute rates of hospitalization were greater (1987-1999: 233.3/1,000; 2000-2012: 320.0/1,000 person years) and death were lesser (1987-1999: 46.3/1,000; 2000-2012: 36.8/1,000 person years) in the later treatment era among cases. Children with solid tumors were less likely to have a cancer-related hospitalization than were those with leukemia/lymphoma (RR 0.91, 95% CI 0.84-0.98).

Conclusion: Even after excluding cancer-related diagnoses, children with cancer experience greater rates of hospitalization and death in all disease categories. Results may guide future toxicity mitigation initiatives and inform anticipatory guidance for families of children with cancer.
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http://dx.doi.org/10.1007/s10552-021-01425-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8215887PMC
July 2021

Pregnancy outcomes among visually impaired women in Washington State, 1987-2014.

Disabil Health J 2021 07 24;14(3):101057. Epub 2020 Dec 24.

Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA; Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Background: Women with visual impairment may have reduced ability to access standard care resources, however, information on their pregnancy and neonatal outcomes is limited.

Objective: To assess risk of adverse pregnancy and neonatal outcomes among visually impaired women in Washington State from 1987 to 2014.

Methods: We conducted a retrospective cohort study using linked Washington State birth/fetal death hospital discharge records to compare outcomes among women with and without visual impairment noted at their delivery hospitalization. Pregnancy conditions and outcomes evaluated included gestational diabetes, pre-eclampsia, labor induction and cesarean delivery. Neonatal outcomes included preterm delivery and birth weight <2500 g. We assessed length of maternal and infant delivery hospitalization. We performed Poisson regression to estimate relative risks (RR) and 95% confidence intervals (CIs) for each outcome, adjusting for year of delivery, maternal age, and parity.

Results: Most adverse pregnancy and neonatal outcomes were similar for visually impaired (N = 232) and comparison women (N = 2362). However, visually impaired women had increased risks of severe pre-eclampsia (RR 3.77, 95% CI 1.69-8.43), labor induction (RR 1.33, 95% CI 1.10-1.61) and preterm delivery (RR 1.60, 95% CI 1.06-2.42). They were also more likely to have delivery hospitalizations of 3 or more days following a vaginal (RR 1.86, 95% CI 1.41-2.47). Among cesarean deliveries, infants of visually impaired women had increased risk (RR 1.24, 95% CI 1.02-1.51) of hospitalization for 3 or more days postpartum.

Conclusion: Our findings may be useful for obstetric providers in counseling their visually impaired patients.
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http://dx.doi.org/10.1016/j.dhjo.2020.101057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8222420PMC
July 2021

Adverse events among chronic myelogenous leukemia patients treated with tyrosine kinase inhibitors: a real-world analysis of health plan enrollees.

Leuk Lymphoma 2021 05 7;62(5):1203-1210. Epub 2020 Dec 7.

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

With tyrosine kinase inhibitor (TKI) therapy, chronic myelogenous leukemia (CML) is now a chronic disease. CML patients treated with TKIs ( = 1200) were identified from the OptumLabs Data Warehouse (de-identified claims and electronic health records) between 2000 and 2016 and compared with a non-cancer cohort ( = 7635). The 5-year cumulative incidence of all organ system outcomes was significantly greater for the TKI versus non-cancer group. In the first year, compared with imatinib, later generation TKIs were associated with primary infections (hazard ratios [HR] 1.43, 95% CI 1.02-2.00), circulatory events (HR 1.15, 95% CI 1.01-1.31), and skin issues (HR 1.43, 95% CI 1.13-1.80); musculoskeletal and nervous system/sensory issues were less common (HRs 0.83-0.84,  < 0.05). Increased risk of infections, cardiopulmonary and skin issues associated with later generation TKIs persisted in subsequent years. In this real-world population, TKI therapy was associated with a high burden of adverse events. Later generation TKIs may have greater toxicity than imatinib.
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http://dx.doi.org/10.1080/10428194.2020.1855340DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106632PMC
May 2021

Feasibility of a behavioral intervention using mobile health applications to reduce cardiovascular risk factors in cancer survivors: a pilot randomized controlled trial.

J Cancer Surviv 2021 Aug 10;15(4):554-563. Epub 2020 Oct 10.

Fred Hutchinson Cancer Research Center, PO Box 19024, Mailstop M4-C308, Seattle, WA, 98109, USA.

Purpose: Determine the feasibility of a remotely delivered mobile health (mHealth)-supported intervention to improve diet and physical activity in hematologic malignancy survivors.

Methods: Pilot randomized controlled trial of a 16-week intervention for improving diet and physical activity: individualized goal-setting (daily steps, sodium, saturated fat, added sugar intake) per feedback from mHealth trackers (Fitbit for activity; Healthwatch360 for diet), supplemented by a Facebook peer support group. Controls accessed the trackers without goal-setting or peer support. Everyone received standardized survivorship counseling with tailored advice from a clinician. Actigraphy and food frequency questionnaires assessed activity and diet at baseline and follow-up.

Results: Forty-one participants (51.2% male; median age 45.1 years; 7.0 years from treatment) were randomized (24 intervention; 17 control). Fitbit and Healthwatch360 use were more common among intervention versus control participants (75.0% versus 70.6% and 50.0% versus 17.7% of eligible days, respectively). Most intervention participants (66.7%) engaged with Facebook; overall, 91.7% interacted with the study's mHealth applications. While no comparisons in activity or dietary outcomes between intervention versus control group met statistical significance, the intervention was associated with greater reductions in the targeted dietary factors and improvements in Healthy Eating Index-2015 score, moderate-vigorous physical activity time, and daily steps. Participant retention at 6 months was 90.2%.

Conclusions: An intervention for cardiovascular risk reduction based on individualized goal-setting enhanced by mHealth and social media peer support was feasible and acceptable among cancer survivors.

Implications For Cancer Survivors: Effective and easily disseminated strategies that improve diet and physical activity in this population are needed.

Trial Registration: Registered in ClinicalTrials.gov (NCT03574012) on June 29, 2018.
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http://dx.doi.org/10.1007/s11764-020-00949-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8035343PMC
August 2021

Humoral Response to HPV16 Proteins in Persons with Anal High-Grade Squamous Intraepithelial Lesion or Anal Cancer.

Cancer Epidemiol Biomarkers Prev 2020 11 3;29(11):2255-2260. Epub 2020 Sep 3.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Background: This study was launched to evaluate the association of early and late antibodies to human papillomavirus 16 (HPV16) detection and risk of anal high-grade squamous intraepithelial lesions (HSIL) or cancer.

Methods: We analyzed data from persons with anal HSIL or cancer and controls from a case-control study in Seattle, Washington. Sera were evaluated for HPV16 early (E1, E2, E4, E6, and E7) and late (L1) antibodies by multiplex serology. Logistic regression models were used to assess serologic associations with risk of anal HSIL or cancer.

Results: The study included 67 participants with anal HSIL, 116 with anal cancer, and 830 population-based controls. HPV16 seropositivity to L1 [adjusted OR (aOR), 13.8; 95% confidence interval (CI), 7.4-25.8], E4 (aOR, 2.3; 95% CI, 1.1-4.5), and E6 (aOR, 4.9; 95% CI, 1.1-21.2) was associated with HSIL; and detection of all antibodies to HPV16 late and early proteins was associated with increased risk of anal cancer ranging from aOR 1.7 to 32.5 [L1 aOR, 12.5 (95% CI, 7.3-21.7); E1 aOR, 24.9 (95% CI, 10.3-59.9); E2 aOR, 6.3 (95% CI, 3.4-11.7); E4 aOR, 2.8 (95% CI, 1.6-4.8); E6 aOR, 32.5 (95% CI, 14.2-74.4); and E7 aOR, 1.7 (95% CI, 1.0-3.0)].

Conclusions: HPV serologic markers proved to be specific for identifying anal cancer. HPV16 E6 seropositivity is relatively uncommon in persons without anal cancer.

Impact: This large study comprehensively describes the distinct antibody responses to the HPV16 proteins in persons with anal HSIL or anal cancer. Antibodies to HPV16 E6 should be further evaluated as a potential biomarker for anal cancer prevention.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0749DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642112PMC
November 2020

Health Care Cost Associated With Contemporary Chronic Myelogenous Leukemia Therapy Compared With That of Other Hematologic Malignancies.

JCO Oncol Pract 2021 03 21;17(3):e406-e415. Epub 2020 Aug 21.

Center for Clinical and Translational Research, Seattle, WA.

Purpose: Given the widespread introduction of tyrosine kinase inhibitors (TKIs), we evaluated the cost associated with chronic myelogenous leukemia (CML) care compared with the cost of care for patients with hematologic malignancies (HEM) and for patients without cancer (GEN), to aid with resource allocation and clinical decision making.

Methods: A retrospective cohort was constructed from the OptumLabs Data Warehouse using claims from 2000 to 2016. Eligible patients had ≥ 2 CML claims and were enrolled continuously for ≥ 6 months before diagnosis and ≥ 1 year afterward (n = 1,909). Patients with CML were frequency matched 4:1 with HEM and GEN cohorts and were observed through October 2017. We used generalized linear models to assess the variation in total mean annualized health care costs in the 3 cohorts and to examine the influence of factors associated with costs.

Results: Mean annualized costs for CML were $82,054 (ie, $25,471 [95% CI, $20,808 to $30,133] more than those for HEM and $74,993 [95% CI, $70,818 to $79,167] more than those for GEN); these differences were driven by pharmacy costs in the CML group. The cost of CML care exceeded that for HEM and GEN for all index years in this study and increased over each diagnostic interval until 2015, peaking at $91,990. The mean annual cost of all TKIs increased. Imatinib's mean annualized cost was $41,546 in the period 2000-2004 but increased to $105,069 in the period 2015-2017. In multivariable analysis, percent days on TKIs had the greatest influence on cost: ≥ 75% of the time versus none showed a difference in cost of $108,716 (95% CI, $99,193 to $118,239).

Conclusion: Contemporary CML costs exceeded the cost of treatment of other hematologic malignancies. Cost was primarily driven by TKIs, whose cost continued to increase over time.
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http://dx.doi.org/10.1200/OP.20.00143DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8189599PMC
March 2021

Dietary fat intake, erythrocyte fatty acids, and risk of uterine fibroids.

Fertil Steril 2020 10 14;114(4):837-847. Epub 2020 Jul 14.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Division of Adolescent and Young Adult Medicine, Department of Medicine, Boston Children's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Obstetrics, Gynecology, and Reproductive Biology, College of Human Medicine, Michigan State University, Grand Rapids, Michigan.

Objective: To prospectively evaluate the association between dietary fat intake and risk of uterine fibroids; and to evaluate the association between erythrocyte membrane fatty acid (FA) levels and fibroid risk.

Design: Prospective cohort study. Cox proportional hazard models were used to calculate hazard ratios and 95% confidence interval (CI). In a subset of participants 34 individual FAs were measured and logistic regression analysis was used to estimate odds ratios (ORs) and 95% CI for the association between FA tertiles and fibroids.

Setting: Not applicable.

Patient(s): Premenopausal US women (81,590) in the Nurses' Health Study II, aged 25-42 years at enrollment in 1989 for whom diet was assessed by a food frequency questionnaire. A total of 553 participants with erythrocyte FA measurements.

Intervention(s): Not applicable.

Main Outcome Measure(s): Cases of fibroids were defined on the basis of self-reported ultrasound or hysterectomy confirmation.

Result(s): A total of 8,142 cases of ultrasound-confirmed or hysterectomy-confirmed were diagnosed during an 18-year period (1991-2009). No associations were observed between intake of any dietary fats and fibroids in the multivariable models. However, when erythrocyte FAs were examined, an inverse association was observed between total n-3 polyunsaturated FAs and likelihood of fibroids (OR for third versus first tertile, 0.41; 95% CI 0.19-0.89). In addition, total trans FAs were associated with more odds of fibroids (OR for third tertile, 3.33; 95% CI 1.50-7.38).

Conclusion(s): Our findings provide preliminary suggestions that n-3 polyunsaturated FAs and trans FAs may play a role in fibroid etiology; however, these results should be confirmed in future studies.
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http://dx.doi.org/10.1016/j.fertnstert.2020.03.023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7554115PMC
October 2020

Birthweight and all-cause mortality after childhood and adolescent leukemia: a cohort of children with leukemia from Denmark, Norway, Sweden, and Washington State.

Acta Oncol 2020 Aug 14;59(8):949-958. Epub 2020 Mar 14.

Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus, Denmark.

High birthweight may predispose children to acute lymphoid leukemia, whereas low birthweight is associated with childhood morbidity and mortality. Low and high birthweight have been inconsistently associated with mortality in children with leukemia. In a cohort of childhood and adolescent leukemia (0-19 years) patients from registries in Denmark, Norway, Sweden, and Washington State in the United States (1967-2015), five-year all-cause mortality was assessed by birthweight and other measures of fetal growth using the cumulative incidence function and Cox regression with adjustment for sex, diagnosis year, country, the presence of Down's syndrome or other malformations, and type of leukemia. Among 7148 children and adolescents with leukemia (55% male), 4.6% were low (<2500 g) and 19% were high (≥4000 g) birthweight. Compared with average weight, hazard ratios (HRs) of death associated with low birthweight varied by age at leukemia diagnosis: 1.5 (95% confidence interval (CI): 0.7, 3.2) for patients 0-1 year old, 1.6 (95% CI: 1.0, 2.6) for >1-2 years old; 1.0 (95% CI: 0.6, 1.5) for 3-8 years old; 1.0 (95% CI: 0.6, 1.8) for 9-13 years old; and 1.2 (95% CI: 0.7, 2.1) for 14-19 years old, and were similar for size for gestational age and Ponderal index. In analyses restricted to children born full term (37-41 weeks of gestation), results were only slightly attenuated but risk was markedly increased for infants aged ≤1 year (HR for low birthweight = 3.2, 95% CI: 1.2, 8.8). This cohort study does not suggest that low birthweight or SGA is associated with increased five-year all-cause mortality risk among children with any type of childhood leukemia or acute lymphoblastic leukemia, specifically, beyond infancy.
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http://dx.doi.org/10.1080/0284186X.2020.1738546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7392817PMC
August 2020

Assessment of the Accuracy of Identification of Selected Disabilities and Conditions in Hospital Discharge Data for Pregnant Women.

Epidemiology 2020 09;31(5):687-691

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Background: Linked birth certificate-hospital discharge records are a valuable resource for examining pregnancy outcomes among women with disability conditions. Few studies relying on these data have been able to assess the accuracy of identification of preexisting disability conditions. We assessed the accuracy of International Classification of Diseases version 9 (ICD9) codes for identifying selected physical, sensory, and intellectual conditions that may result in disability. As ICD9 codes were utilized until recently in most states, this information is useful to inform analyses with these records.

Methods: We reviewed 280 of 311 (90%) medical records of pregnant women with disabilities based on ICD9 codes and 390 of 8,337 (5%) records of pregnant women without disabilities who had deliveries at a large university medical center. We estimated sensitivity, specificity, and positive predictive values (PPV) using the medical record as gold standard. We adjusted for verification bias using inverse probability weighting and imputation.

Results: The estimated sensitivity of ICD9 codes to identify women with disabilities with deliveries 2009-2012 was 44%; PPV was 98%, improving over time. Although sensitivity was <50% for some conditions, PPVs were 87%-100% for all conditions except intellectual disability (67%). Many physical conditions had complete verification and no underreporting.

Conclusions: These results are helpful for new studies using historical data comparing outcomes among women with and without these conditions and to inform interpretation of results from earlier studies. Assessment of the accuracy of disabilities as identified by ICD version 10 codes is warranted.
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http://dx.doi.org/10.1097/EDE.0000000000001185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8323995PMC
September 2020

Age-, sex- and disease subtype-related foetal growth differentials in childhood acute myeloid leukaemia risk: A Childhood Leukemia International Consortium analysis.

Eur J Cancer 2020 05 9;130:1-11. Epub 2020 Mar 9.

Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden. Electronic address:

Aim: Evidence for an association of foetal growth with acute myeloid leukaemia (AML) is inconclusive. AML is a rare childhood cancer, relatively more frequent in girls, with distinct features in infancy. In the context of the Childhood Leukemia International Consortium (CLIC), we examined the hypothesis that the association may vary by age, sex and disease subtype using data from 22 studies and a total of 3564 AML cases.

Methods: Pooled estimates by age, sex and overall for harmonised foetal growth markers in association with AML were calculated using the International Fetal and Newborn Growth Consortium for the 21st Century Project for 17 studies contributing individual-level data; meta-analyses were, thereafter, conducted with estimates provided ad hoc by five more studies because of administrative constraints. Subanalyses by AML subtype were also performed.

Results: A nearly 50% increased risk was observed among large-for-gestational-age infant boys (odds ratio [OR]: 1.49, 95% confidence interval [CI]: 1.03-2.14), reduced to 34% in boys aged <2 years (OR: 1.34, 95% CI: 1.05-1.71) and 25% in boys aged 0-14 years (OR: 1.25, 95% CI: 1.06-1.46). The association of large for gestational age became stronger in boys with M0/M1subtype (OR: 1.80, 95% CI: 1.15-2.83). Large birth length for gestational age was also positively associated with AML (OR: 1.38, 95% CI: 1.00-1.92) in boys. By contrast, there were null associations in girls, as well as with respect to associations of decelerated foetal growth markers.

Conclusions: Accelerated foetal growth was associated with AML, especially in infant boys and those with minimally differentiated leukaemia. Further cytogenetic research would shed light into the underlying mechanisms.
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http://dx.doi.org/10.1016/j.ejca.2020.01.018DOI Listing
May 2020

Parental age and the risk of childhood acute myeloid leukemia: results from the Childhood Leukemia International Consortium.

Cancer Epidemiol 2019 04 15;59:158-165. Epub 2019 Feb 15.

Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, Athens, Greece; Clinical Epidemiology Unit, Department of Medicine, Karolinska Institute, Stockholm, Sweden. Electronic address:

Background: Parental age has been associated with several childhood cancers, albeit the evidence is still inconsistent.

Aim: To examine the associations of parental age at birth with acute myeloid leukemia (AML) among children aged 0-14 years using individual-level data from the Childhood Leukemia International Consortium (CLIC) and non-CLIC studies.

Material/methods: We analyzed data of 3182 incident AML cases and 8377 controls from 17 studies [seven registry-based case-control (RCC) studies and ten questionnaire-based case-control (QCC) studies]. AML risk in association with parental age was calculated using multiple logistic regression, meta-analyses, and pooled-effect estimates. Models were stratified by age at diagnosis (infants <1 year-old vs. children 1-14 years-old) and by study design, using five-year parental age increments and controlling for sex, ethnicity, birthweight, prematurity, multiple gestation, birth order, maternal smoking and education, age at diagnosis (cases aged 1-14 years), and recruitment time period.

Results: Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) derived from RCC, but not from the QCC, studies showed a higher AML risk for infants of mothers ≥40-year-old (OR = 6.87; 95% CI: 2.12-22.25). There were no associations observed between any other maternal or paternal age group and AML risk for children older than one year.

Conclusions: An increased risk of infant AML with advanced maternal age was found using data from RCC, but not from QCC studies; no parental age-AML associations were observed for older children.
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http://dx.doi.org/10.1016/j.canep.2019.01.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7098424PMC
April 2019

Pregnancy Outcomes in Women with Spinal Cord Injuries: A Population-Based Study.

PM R 2019 08 26;11(8):795-806. Epub 2019 Apr 26.

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

Background: Pregnant women with congenital or acquired spinal cord injury face challenges due to compromised neurologic function and mobility, factors that may also affect fetal/infant health. Few studies have examined pregnancy course and longer-term outcomes in this population.

Objective: To assess pregnancy outcomes among women with spinal cord injury, paralysis, or spina bifida using population-based data.

Design: Retrospective cohort study.

Setting: Washington state linked birth-hospital discharge records.

Participants: All women (N = 529) with spinal cord injury, paralysis, or spina bifida with singleton live birth deliveries 1987-2012, and a comparison group of women without disabilities (N = 5282).

Methods: Diagnosis codes were screened to identify cases and a 10:1 random sample of comparison women. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated overall and separately for each condition using multivariable regression. Subsequent hospitalizations or death were identified via linkage to hospital discharge/death records for 2 years after delivery.

Main Outcome Measurements: Pregnancy course (weight gain, gestational diabetes, preeclampsia, infection, venous thromboembolism), delivery/labor characteristics, infant characteristics (birthweight/size, gestational age), and longer-term outcomes (occurrence/reasons for maternal/infant rehospitalization, mortality).

Results: Women with these spinal conditions had increased adjusted risks of prenatal urinary tract infection/pyelonephritis (RR 26.43, 95% CI 13.97-49.99), venous thromboembolism (RR 9.16, 95% CI 2.17-38.60), preterm rupture of membranes (RR 2.15, 95% CI 1.18-3.90), and cesarean delivery (RR 1.88, 95% CI 1.70-2.09). They had longer hospitalizations and increased rehospitalization (RR 1.54, 95% CI 1.28-1.87), including for postpartum depression (RR 8.15, 4.29-15.48) or injury (RR 13.05, 95% CI 6.60-25.81). Their infants were more often small for gestational age (RR 1.65, 95% CI 1.33-2.06), but had no increased risk of rehospitalization or death.

Conclusions: We observed no increased long-term morbidity among infants of women with these conditions. Possible increased maternal morbidities during the first postpartum years indicate areas for intervention.

Level Of Evidence: III.
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http://dx.doi.org/10.1002/pmrj.12122DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6675642PMC
August 2019

Pregnancy course, infant outcomes, rehospitalization, and mortality among women with intellectual disability.

Disabil Health J 2019 07 20;12(3):452-459. Epub 2019 Jan 20.

Department of Epidemiology, University of Washington, Seattle, WA, USA.

Background: Pregnant women with intellectual disability (ID) may have greater levels of comorbidity and decreased care access, social support, or ability to monitor their status and communicate needs, but few studies have examined their pregnancy course and outcome, and little is known about their longer-term maternal and infant health.

Objective: We compared pre-pregnancy characteristics, pregnancy outcomes, and rehospitalization <2 years after delivery among women with and without ID.

Method: We identified all women with ID and randomly selected a 10:1 comparison group of women without ID with singleton live birth deliveries in Washington State population-based linked birth-hospital discharge data 1987-2012. Multivariable regressions estimated adjusted odds ratios comparing pre-pregnancy characteristics. In cohort analyses, we estimated relative risks (RR) and 95% confidence intervals (CI) for outcomes.

Results: Women with ID (N = 103) more often had gestational diabetes (RR 3.39, 95% CI 1.81-6.37), preeclampsia (RR 1.88, 95% CI 1.03-3.42), and inadequate prenatal care (RR 2.48, 95% CI 1.67-3.70). Their infants more often were small for gestational age (RR 1.78, 95% CI 1.10-2.89). Need for rehospitalization postpartum was not increased among women with ID or their infants.

Conclusion: Reasons for increased preeclampsia and gestational diabetes among pregnant women with ID are unclear. Barriers to inadequate prenatal care are multifactorial and warrant further study, with consideration that wellness during pregnancy and other times involves social, familial and clinical support systems responsive to each woman's needs.
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http://dx.doi.org/10.1016/j.dhjo.2019.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6581578PMC
July 2019

CYP2D6-inhibiting medication use and inherited CYP2D6 variation in relation to adverse breast cancer outcomes after tamoxifen therapy.

Cancer Causes Control 2019 Jan 12;30(1):103-112. Epub 2018 Dec 12.

University of Washington, Seattle, WA, USA.

Purpose: Tamoxifen is widely used to reduce the risk of breast cancer (BC) recurrence and extend disease-free survival among women with estrogen-sensitive breast cancers. Tamoxifen efficacy is thought to be attributable to its active metabolite, which is formed through a reaction catalyzed by the P450 enzyme, CYP2D6. Inhibition of tamoxifen metabolism as a result of germline genetic variation and/or use of CYP2D6-inhibiting medications ("inhibitors") is hypothesized to increase the risk of adverse BC outcomes among women taking tamoxifen.

Methods: The present cohort study of 960 women diagnosed with early-stage BC between 1993 and 1999 examined the association between concomitant use of CYP2D6 inhibitors and adjuvant tamoxifen and the risk of adverse BC outcomes (recurrence, second primary BC, BC mortality), both overall and according to CYP2D6 metabolic phenotype.

Results: Six or more months of CYP2D6 inhibitor use concomitant with tamoxifen was not associated with any appreciable increase in risk of recurrence or second primary BC or BC mortality, and there was no clear evidence of variation by CYP2D6 metabolic phenotype.

Conclusions: These results are consistent with the relatively few other large, population-based studies conducted to date that have not observed an increased risk of adverse BC outcomes associated with CYP2D6 inhibition.
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http://dx.doi.org/10.1007/s10552-018-1117-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6353670PMC
January 2019

CYP2D6 phenotype, tamoxifen, and risk of contralateral breast cancer in the WECARE Study.

Breast Cancer Res 2018 12 10;20(1):149. Epub 2018 Dec 10.

Memorial Sloan Kettering Cancer Center, New York, NY, USA.

Background: Tamoxifen treatment greatly reduces a woman's risk of developing a second primary breast cancer. There is, however, substantial variability in treatment response, some of which may be attributed to germline genetic variation. CYP2D6 is a key enzyme in the metabolism of tamoxifen to its active metabolites, and variants in this gene have been associated with reduced tamoxifen metabolism. The impact of variation on risk of contralateral breast cancer (CBC) is unknown.

Methods: Germline DNA from 1514 CBC cases and 2203 unilateral breast cancer controls was genotyped for seven single nucleotide polymorphisms, one three-nucleotide insertion-deletion, and a full gene deletion. Each variant has an expected impact on enzyme activity, which in combination allows for the classification of women as extensive, intermediate, and poor metabolizers (EM, IM, and PM respectively). Each woman was assigned one of six possible diplotypes and a corresponding CYP2D6 activity score (AS): EM/EM (AS = 2), EM/IM (AS = 1.5), EM/PM (AS = 1), IM/IM (AS = 0.75), IM/PM (AS = 0.5), and PM/PM (AS = 0). We also collapsed categories of the AS to generate an overall phenotype (EM, AS ≥ 1; IM, AS = 0.5-0.75; PM, AS = 0). Rate ratios (RRs) and 95% confidence intervals (CIs) for the association between tamoxifen treatment and risk of CBC in our study population were estimated using conditional logistic regression, stratified by AS.

Results: Among women with AS ≥ 1 (i.e., EM), tamoxifen treatment was associated with a 20-55% reduced RR of CBC (AS = 2, RR = - 0.81, 95% CI 0.62-1.06; AS = 1.5, RR = 0.45, 95% CI 0.30-0.68; and AS = 1, RR = 0.55, 95% CI 0.40-0.74). Among women with no EM alleles and at least one PM allele (i.e., IM and PM), tamoxifen did not appear to impact the RR of CBC in this population (AS = 0.5, RR = 1.08, 95% CI 0.59-1.96; and AS = 0, RR = 1.17, 95% CI 0.58-2.35) (p for homogeneity = - 0.02).

Conclusion: This study suggests that the CYP2D6 phenotype may contribute to some of the observed variability in the impact of tamoxifen treatment for a first breast cancer on risk of developing CBC.
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http://dx.doi.org/10.1186/s13058-018-1083-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6288916PMC
December 2018

Hospitalization and mortality among pediatric cancer survivors: a population-based study.

Cancer Causes Control 2018 Nov 5;29(11):1047-1057. Epub 2018 Sep 5.

Public Health Sciences Division, Fred Hutchinson Cancer Research Center (FHCRC), PO 19024, Mailstop M4-C308, Seattle, WA, USA.

Purpose: We examined serious long-term outcomes among childhood cancer survivors using population-based data.

Methods: We used 1982-2014 Washington State data to compare hospitalization and/or death (including cause-specific) during up to 27 years follow-up among all 5+ year childhood cancer survivors < 20 years at diagnosis (n = 3,152) and a sample of comparison children within birth cohorts, with assessment by cancer type and child/family characteristics.

Results: During follow-up (9 years median), 12% of survivors had hospitalizations; 4% died. Greatest absolute risks/1,000 person-years were for hospitalization/deaths due to cancers (8.1), infection (6.2), injuries (6.0), and endocrine/metabolic disorders (5.8). Hazard ratios (HR) and 95% confidence intervals (CI) for hospitalization (2.7, 95% CI 2.4-3.0) and any-cause death (14.7, 95% CI 11.3-19.1) were increased, and for all cause-specific outcomes examined, most notably cancer- (35.1, 95% CI 23.7-51.9), hematological- (6.7, 95% CI 5.3-8.5), nervous system- (6.4, 95% CI 5.2-7.8), and circulatory- (5.2, 95% CI 4.1-6.5) related outcomes. Hospitalizations occurred more often among females and those receiving radiation, with modest differences by urban/rural birth residence and race/ethnicity. Cause-specific outcomes varied by cancer type.

Conclusions: This study suggests increased risks for the rarely-studied outcomes of long-term fracture and injury, and confirms increased risks of selected other conditions among survivors. Multi-state pooling of population-based data would increase the ability to evaluate outcomes for uncommon cancer types and by racial/ethnic groups under-represented in many studies.
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http://dx.doi.org/10.1007/s10552-018-1078-0DOI Listing
November 2018

Advanced parental age as risk factor for childhood acute lymphoblastic leukemia: results from studies of the Childhood Leukemia International Consortium.

Eur J Epidemiol 2018 Oct 14;33(10):965-976. Epub 2018 May 14.

Department of Women's and Children's Health, Uppsala University, Uppsala, Sweden.

Advanced parental age has been associated with adverse health effects in the offspring including childhood (0-14 years) acute lymphoblastic leukemia (ALL), as reported in our meta-analysis of published studies. We aimed to further explore the association using primary data from 16 studies participating in the Childhood Leukemia International Consortium. Data were contributed by 11 case-control (CC) studies (7919 cases and 12,942 controls recruited via interviews) and five nested case-control (NCC) studies (8801 cases and 29,690 controls identified through record linkage of population-based health registries) with variable enrollment periods (1968-2015). Five-year paternal and maternal age increments were introduced in two meta-analyses by study design using adjusted odds ratios (OR) derived from each study. Increased paternal age was associated with greater ALL risk in the offspring (OR 1.05, 95% CI 1.00-1.11; OR 1.04, 95% CI 1.01-1.07). A similar positive association with advanced maternal age was observed only in the NCC results (OR 0.99, 95% CI 0.91-1.07, heterogeneity I = 58%, p = 0.002; OR 1.05, 95% CI 1.01-1.08). The positive association between parental age and risk of ALL was most marked among children aged 1-5 years and remained unchanged following mutual adjustment for the collinear effect of the paternal and maternal age variables; analyses of the relatively small numbers of discordant paternal-maternal age pairs were not fully enlightening. Our results strengthen the evidence that advanced parental age is associated with increased childhood ALL risk; collinearity of maternal with paternal age complicates causal interpretation. Employing datasets with cytogenetic information may further elucidate involvement of each parental component and clarify underlying mechanisms.
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http://dx.doi.org/10.1007/s10654-018-0402-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6384148PMC
October 2018

Bisphosphonate Use and Risk of Recurrence, Second Primary Breast Cancer, and Breast Cancer Mortality in a Population-Based Cohort of Breast Cancer Patients.

Cancer Epidemiol Biomarkers Prev 2018 02 18;27(2):165-173. Epub 2017 Dec 18.

Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Studies of bisphosphonate use and breast cancer recurrence have produced conflicting results. Analyses of large adjuvant trials suggest that bisphosphonates reduce recurrence risk only in postmenopausal women. We assessed the effect of noncancer treatment-related bisphosphonate use on breast cancer outcomes in a population-based prognostic cohort of women with early-stage invasive breast cancer ( = 1,813; median follow-up = 11.8 years). Using medical record, interview, and cancer registry data, information was assembled on risk factors, cancer treatment, medication use, and outcomes. Statistical analyses used Cox proportional hazards regression models. Bisphosphonate use was associated with a significantly decreased risk of a breast cancer event [locoregional/distant recurrence or second primary breast cancer; HR ever use, 0.65; 95% confidence interval (CI), 0.47-0.90]. Reduced risks were observed in both pre/peri and postmenopausal women, in both ER-negative and ER-positive breast cancers, and for both earlier and later recurrences. Bisphosphonate use was also associated with a significantly decreased risk of breast cancer mortality (HR, 0.40; 95% CI, 0.23-0.69). Bisphosphonate use was associated with a reduction in risk of breast cancer events and improved breast cancer-specific survival in women with early-stage breast cancer. We hypothesize that the benefit of bisphosphonates on breast cancer outcomes may be present primarily in women with low bone density and regardless of menopausal status. Our findings suggest further consideration of bone density status as a modifier of bisphosphonate's potential beneficial benefits on breast cancer outcomes is warranted. .
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http://dx.doi.org/10.1158/1055-9965.EPI-17-0556DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6021196PMC
February 2018

Pregnancy Outcomes Among Deaf Women in Washington State, 1987-2012.

Obstet Gynecol 2017 11;130(5):953-960

Department of Epidemiology, School of Public Health, and the Departments of Obstetrics and Gynecology and Rehabilitation Medicine, School of Medicine, University of Washington, and the Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington.

Objective: To evaluate pregnancy and neonatal outcomes among deaf women using population-based vital records data in Washington State from 1987 to 2012.

Methods: We performed a retrospective cohort study using the Washington State birth and fetal death records linked to state hospital discharge records to identify women with diagnosis codes for deafness indicated at their delivery hospitalization and compared them with randomly selected women without these codes. Pregnancy conditions and outcomes evaluated included gestational diabetes, preeclampsia, placental abruption, labor induction, and cesarean delivery. Neonatal outcomes evaluated included preterm gestational age (less than 28, 28 to less than 37 weeks) at delivery and low birth weight. We also assessed length of maternal and neonatal delivery hospitalization. We performed Poisson regression to estimate relative risks (RRs) and 95% CIs for each outcome, adjusting for birth year, maternal age, and parity.

Results: Most adverse pregnancy and neonatal outcomes were similar for deaf and comparison women. Among women who underwent vaginal delivery, deaf women were more than twofold (RR 2.15, 95% CI 1.43-3.22) more likely to have a delivery hospitalization of 4 or more days (6.0% compared with 2.8%). We found a modestly increased risk of cesarean delivery (RR 1.15, 95% CI 1.01-1.30), with 29.9% of deaf compared with 25.6% of nondeaf women having a cesarean delivery.

Conclusion: Deaf women are not at increased risk of the majority of adverse pregnancy and neonatal outcomes. Obstetric care providers may use our findings in counseling this special population of prenatal patients.
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http://dx.doi.org/10.1097/AOG.0000000000002321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5958610PMC
November 2017

Childhood cancer risk in those with chromosomal and non-chromosomal congenital anomalies in Washington State: 1984-2013.

PLoS One 2017 8;12(6):e0179006. Epub 2017 Jun 8.

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America.

Background: The presence of a congenital anomaly is associated with increased childhood cancer risk, likely due to large effects of Down syndrome and chromosomal anomalies for leukemia. Less is known about associations with presence of non-chromosomal anomalies.

Methods: Records of children diagnosed with cancer at <20 years of age during 1984-2013 in Washington State cancer registries were linked to their birth certificates (N = 4,105). A comparison group of children born in the same years was identified. Congenital anomalies were assessed from birth records and diagnosis codes in linked hospital discharge data. Logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for cancer, and for specific cancer types in relation to the presence of any anomaly and specific anomalies.

Results: Having any congenital anomaly was associated with an increased risk of childhood cancer (OR: 1.46, 95% CI 1.28-1.65). Non-chromosomal anomalies were also associated with increased childhood cancer risk overall (OR: 1.35; 95% CI: 1.18-1.54), and with increased risk of several cancer types, including neuroblastoma, renal, hepatoblastoma, soft-tissue sarcoma, and germ cell tumors. Increasing number of non-chromosomal anomalies was associated with a stronger risk of childhood cancer (OR for 3+ anomalies: 3.11, 95% CI: 1.54-6.11). Although central nervous system (CNS) anomalies were associated with CNS tumors (OR: 6.05, 95% CI 2.75-13.27), there was no strong evidence of other non-chromosomal anomalies being specifically associated with cancer occurring in the same organ system or anatomic location.

Conclusions: Non-chromosomal anomalies increased risk of several cancer types. Additionally, we found that increasing number of non-chromosomal anomalies was associated with a stronger risk of cancer. Pooling similar data from many regions would increase power to identify specific associations in order to inform molecular studies examining possible common developmental pathways in the etiologies of birth defects and cancer.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0179006PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464621PMC
September 2017

Knowledge of Clinical Trial Availability and Reasons for Nonparticipation Among Adolescent and Young Adult Cancer Patients: A Population-based Study.

Am J Clin Oncol 2018 06;41(6):581-587

Epidemiology Program, Fred Hutchinson Cancer Research Center, Seattle, WA.

Purpose Of The Study: Adolescent and young adult (AYA) cancer patients are underrepresented in clinical trials, but the reasons for this phenomenon are unknown.

Patients And Methods: Questionnaire and medical record data from 515 AYA cancer patients (21 acute lymphocytic leukemia [ALL], 201 germ cell tumor, 141 Hodgkin lymphoma, 128 non-Hodgkin lymphoma, 24 sarcoma) from a population-based study were analyzed. We used multivariable models to determine characteristics associated with patient knowledge of the availability of clinical trials for their cancer. Reasons for not participating in a trial were tabulated.

Results: In total, 63% of patients reported not knowing whether a relevant clinical trial was available, 20% reported knowing that a clinical trial was not available, and 17% reported that a trial was available. Among patients reporting an available trial, 67% were recommended for enrollment. Knowing about the availability of clinical trials was associated with having ALL (odds ratio=2.9, 95% confidence interval=1.1, 7.8). Reporting that a clinical trial was available was positively associated with having ALL, Hodgkin lymphoma, non-Hodgkin lymphoma and sarcoma (relative to germ cell tumor) and working full-time or in school full-time (odds ratio=2.6, 95% confidence interval=1.0, 6.7). Concerns about involvement in research (57%) and problems accessing trials (21%) were the primary reasons cited for not enrolling among patients who knew that a trial was available.

Conclusions: Improvement in AYA cancer patient clinical trial enrollment will require enhancing knowledge about trial availability and addressing this population's concerns about participating in medical research.
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http://dx.doi.org/10.1097/COC.0000000000000327DOI Listing
June 2018

Parental Tobacco Smoking and Acute Myeloid Leukemia: The Childhood Leukemia International Consortium.

Am J Epidemiol 2016 08 3;184(4):261-73. Epub 2016 Aug 3.

The association between tobacco smoke and acute myeloid leukemia (AML) is well established in adults but not in children. Individual-level data on parental cigarette smoking were obtained from 12 case-control studies from the Childhood Leukemia International Consortium (CLIC, 1974-2012), including 1,330 AML cases diagnosed at age <15 years and 13,169 controls. We conducted pooled analyses of CLIC studies, as well as meta-analyses of CLIC and non-CLIC studies. Overall, maternal smoking before, during, or after pregnancy was not associated with childhood AML; there was a suggestion, however, that smoking during pregnancy was associated with an increased risk in Hispanics (odds ratio = 2.08, 95% confidence interval (CI): 1.20, 3.61) but not in other ethnic groups. By contrast, the odds ratios for paternal lifetime smoking were 1.34 (95% CI: 1.11, 1.62) and 1.18 (95% CI: 0.92, 1.51) in pooled and meta-analyses, respectively. Overall, increased risks from 1.2- to 1.3-fold were observed for pre- and postnatal smoking (P < 0.05), with higher risks reported for heavy smokers. Associations with paternal smoking varied by histological type. Our analyses suggest an association between paternal smoking and childhood AML. The association with maternal smoking appears limited to Hispanic children, raising questions about ethnic differences in tobacco-related exposures and biological mechanisms, as well as study-specific biases.
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http://dx.doi.org/10.1093/aje/kww018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4983653PMC
August 2016

Consumption of alcoholic beverages in adolescence and adulthood and risk of testicular germ cell tumor.

Int J Cancer 2016 12 16;139(11):2405-14. Epub 2016 Aug 16.

Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, WA.

The etiology of testicular germ cell tumor (TGCT) remains obscure and accumulating evidence suggests that postnatal environmental or lifestyle factors may play a role. To investigate whether consumption of alcoholic beverages during adolescence or adulthood is associated with TGCT risk, we analyzed data from a USA population-based case-control study of 540 18-44 year-old TGCT cases and 1,280 age-matched controls. Participants were queried separately about consumption of beer, wine and liquor during grades 7-8, grades 9-12 and the 5 years before reference date (date of diagnosis for cases and corresponding date for controls). We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association of TGCT risk with alcoholic beverage consumption during the different periods, both total and by specific beverage types and separately for seminomas and nonseminomas. Compared with nondrinkers in the 5 years before reference date, the OR (95% CI) for 1-6, 7-13 and ≥14 drinks per week were 1.20 (0.85, 1.69), 1.23 (0.81, 1.85) and 1.56 (1.03, 2.37), respectively (p-trend = 0.04). The corresponding results for alcohol consumption in grades 9-12 were 1.39 (1.06, 1.82), 1.07 (0.72, 1.60), 1.53 (1.01, 2.31) (p-trend = 0.05). Alcohol consumption in grades 7-8 was uncommon and no statistically significant associations with TGCT were observed. Associations with alcohol consumption in the 5 years before reference date appeared stronger for nonseminomas than for seminomas, but the differences were not statistically significant (p≥0.10). Associations were similar across different alcoholic beverage types. Consumption of alcoholic beverages may be associated with an increased TGCT risk.
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http://dx.doi.org/10.1002/ijc.30368DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5618434PMC
December 2016

Natural Antibodies to Human Papillomavirus 16 and Recurrence of Vulvar High-Grade Intraepithelial Neoplasia (VIN3).

J Low Genit Tract Dis 2016 Jul;20(3):257-60

1Public Health Science, Fred Hutchinson Cancer Research Center, Seattle, WA; 2Department of Epidemiology, University of Washington, Seattle, WA; 3Human Biology, Fred Hutchinson Cancer Research Center, Seattle, WA; and 4Department of Microbiology, University of Washington, Seattle, WA.

Objectives: Approximately 30% of women treated for squamous high-grade intraepithelial neoplasia (VIN3), often associated with human papillomavirus (HPV), have recurrent disease. In this study, we assess predictors of recurrence that may provide targets for early prevention or treatment.

Materials And Methods: Women with VIN3 who participated in a previous population-based case-control study with blood and tumor samples completed a follow-up telephone interview an average of 5 years after initial diagnosis. The risk of recurrence was determined by proportional hazards modeling.

Results: Women with VIN3 in the follow-up study (n = 65) were similar to women with VIN3 in the parent study (n = 215) with regard to age at primary diagnosis, level of current cigarette smoking (>60%), and lifetime number of partners. We found that 22 (33.8%) of 65 participants had a vulvar recurrence and that 73.4% recurred within 3 years of treatment. Recurrences occurred more often among women with common warts in the decade before diagnosis (hazard ratio [HR] = 2.5, 95% CI = 1.1-5.8) and among those with a previous anogenital cancer (HR = 2.7, 95% CI = 1.2-6.3). Interestingly, recurrence was less frequent among women who mounted a natural antibody response to HPV16 (HR = 0.4, 95% CI = 0.2-0.9).

Conclusions: These data provide strong preliminary evidence that VIN3 recurrence was less frequent among those with HPV16 antibodies. Vaccination with the currently licensed HPV vaccine as part of adjunctive therapy for VIN3 would increase antibody response and may decrease risk of recurrence. Randomized controlled trials are needed to determine whether HPV vaccination is effective against VIN3 recurrence.
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http://dx.doi.org/10.1097/LGT.0000000000000227DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4920724PMC
July 2016

Genome-Wide Loss of Heterozygosity and DNA Copy Number Aberration in HPV-Negative Oral Squamous Cell Carcinoma and Their Associations with Disease-Specific Survival.

PLoS One 2015 6;10(8):e0135074. Epub 2015 Aug 6.

Program in Biostatistics and Biomathematics, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, United States of America; Department of Genetics and Genomics Sciences, Mt. Sinai School of Medicine, New York, New York, United States of America.

Oral squamous cell cancer of the oral cavity and oropharynx (OSCC) is associated with high case-fatality. For reasons that are largely unknown, patients with the same clinical and pathologic staging have heterogeneous response to treatment and different probability of recurrence and survival, with patients with Human Papillomavirus (HPV)-positive oropharyngeal tumors having the most favorable survival. To gain insight into the complexity of OSCC and to identify potential chromosomal changes that may be associated with OSCC mortality, we used Affymtrix 6.0 SNP arrays to examine paired DNA from peripheral blood and tumor cell populations isolated by laser capture microdissection to assess genome-wide loss of heterozygosity (LOH) and DNA copy number aberration (CNA) and their associations with risk factors, tumor characteristics, and oral cancer-specific mortality among 75 patients with HPV-negative OSCC. We found a highly heterogeneous and complex genomic landscape of HPV-negative tumors, and identified regions in 4q, 8p, 9p and 11q that seem to play an important role in oral cancer biology and survival from this disease. If confirmed, these findings could assist in designing personalized treatment or in the creation of models to predict survival in patients with HPV-negative OSCC.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0135074PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4527746PMC
May 2016

Late Mortality After Dexrazoxane Treatment: A Report From the Children's Oncology Group.

J Clin Oncol 2015 Aug 26;33(24):2639-45. Epub 2015 May 26.

Eric J. Chow, David R. Doody, Wendy M. Leisenring, and K. Scott Baker, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington, Seattle, WA; Barbara L. Asselin and Louis S. Constine, University of Rochester Medical Center and School of Medicine, Rochester, NY; Cindy L. Schwartz, University of Texas MD Anderson Cancer Center, Houston, TX; Sanjeev Aggarwal and Steven E. Lipshultz, Children's Hospital of Michigan, Wayne State University, Detroit, MI; Smita Bhatia, University of Alabama, Birmingham, AL; David R. Freyer, Children's Hospital Los Angeles, University of Southern California, Los Angeles; and Saro H. Armenian, City of Hope Cancer Center, Duarte, CA.

Purpose: Given concerns that dexrazoxane may reduce treatment efficacy, induce second cancers, and thus compromise overall survival among children, we examined long-term overall and cause-specific mortality and disease relapse rates from three randomized clinical trials.

Patients And Methods: Children's Oncology Group trials P9404 (T-cell acute lymphoblastic leukemia/lymphoma; n = 537), P9425 (intermediate/high-risk Hodgkin lymphoma; n = 216), and P9426 (low-risk Hodgkin lymphoma; n = 255) were conducted between 1996 and 2001. Each trial randomly assigned patients to doxorubicin with or without dexrazoxane. The dexrazoxane:doxorubicin dose ratio was 10:1, and the cumulative protocol-specified doxorubicin dose was 100 to 360 mg/m(2). Dexrazoxane was given as an intravenous bolus before each doxorubicin dose. Data from all three trials were linked with the National Death Index to determine overall and cause-specific mortality by dexrazoxane status.

Results: Among 1,008 patients (507 received dexrazoxane) with a median follow-up of 12.6 years (range, 0 to 15.5 years), 132 died (67 received dexrazoxane). Overall mortality did not vary by dexrazoxane status (12.8% with dexrazoxane at 10 years v 12.2% without; hazard ratio [HR], 1.03; 95% CI, 0.73 to 1.45). Findings were similar when each trial was examined separately. Dexrazoxane also was not significantly associated with differential causes of death. The original cancer caused 76.5% of all deaths (HR, 0.90; 95% CI, 0.61 to 1.32) followed by second cancers (13.6% of deaths; HR, 1.24; 95% CI, 0.49 to 3.15). Specifically, dexrazoxane was not associated with deaths from acute myeloid leukemia/myelodysplasia or cardiovascular events.

Conclusion: Among pediatric patients with leukemia or lymphoma, after extended follow-up, dexrazoxane use did not seem to compromise long-term survival.
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http://dx.doi.org/10.1200/JCO.2014.59.4473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4534526PMC
August 2015

Response to "importance of C-3 epimer of 25-hydroxyvitamin D in dried blood spots of neonatal population".

Int J Cancer 2015 Aug 2;137(3):751. Epub 2015 Feb 2.

Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA.

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http://dx.doi.org/10.1002/ijc.29422DOI Listing
August 2015

Neonatal vitamin D and childhood brain tumor risk.

Int J Cancer 2015 May 9;136(10):2481-5. Epub 2014 Nov 9.

Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA; Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA.

Vitamin D deficiency among pregnant women is common. Compelling animal evidence suggests carcinogenic effects of vitamin D deficiency on the brains of offspring; however, the impact of circulating vitamin D [25(OH)D] on childhood brain tumor (CBT) risk has not been previously evaluated. Using linked birth-cancer registry data in Washington State, 247 CBT cases (<15 years at diagnosis; born 1991 or later) were identified. A total of 247 birth year-, sex- and race-matched controls were selected from the remaining birth certificates. Liquid chromatography-tandem mass spectrometry was used to measure circulating levels of vitamin D3 [25(OH)D3] in neonatal dried blood spots. Overall, no significant associations were observed. However, when stratified by median birth weight (3,458 g), there was evidence of increasing risk of CBT with increasing 25(OH)D3 among children in the higher birth weight category. Compared to the lowest quartile (2.8-7.7 ng/mL), odds ratios (ORs) and 95% confidence intervals (CIs) for the second (7.7-<11.0 ng/mL), third (11.0-<14.7 ng/mL) and fourth (14.7-37.0) quartiles of 25(OH)D3 were 1.7 (1.0-3.3), 2.4 (1.2-4.8) and 2.6 (1.2-5.6), respectively. Among children in the lower birth weight category, there was suggestive evidence of a protective effect: ORs and 95% CIs for the second, third and fourth quartiles were 0.9 (0.4-1.9), 0.7 (0.3-1.4) and 0.6 (0.3-1.3), respectively. Any associations of neonatal vitamin D with CBT may be birth weight-specific, suggesting the possible involvement of insulin-like growth factor 1, circulating levels of which have been associated with vitamin D and accelerated fetal growth.
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http://dx.doi.org/10.1002/ijc.29291DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4355103PMC
May 2015
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