Publications by authors named "Norman E Breslow"

50 Publications

Estimating the hazard rate difference from case-cohort studies.

Eur J Epidemiol 2021 Jun 14. Epub 2021 Jun 14.

Department of Biostatistics, University of Washington, Seattle, WA, 98105, USA.

The case-cohort design, among many two-phase sampling designs, substantially reduces the cost of an epidemiological study by selecting more informative participants within the full cohort for expensive variable measurements. Despite their benefits, additive hazards models, which estimate hazard differences, have rarely been used for the analysis of case-cohort studies due to the lack of software and application examples. In this paper, we describe a newly developed estimation method that fits the additive hazards models to general two-phase sampling studies along with the R package addhazard that implements it. It allows for missing covariates among cases, cohort stratification, robust variances, and the incorporation of auxiliary information from the full cohort to enhance inference precision. We demonstrate the use of this tool to estimate the association of the risk of coronary heart disease (CHD) with biomarkers high-sensitivity C-reactive protein (hs-CRP) and Lipoprotein-associated phospholipase A (Lp-PLA) by analyzing the Atherosclerosis Risk in Communities Study, which adopted a two-phase sampling design for studying these two biomarkers. We show that the use of auxiliary variables from the full cohort based on calibration techniques improves the precision of the hazard difference being estimated. We observe a synergistic effect of the two biomarkers among participants with lower LDL cholesterol (LDL-C): the CHD hazard rate attributable to the combined action of high hs-CRP and high Lp-PLA exceeded the sum of the CHD hazard rate attributable to each one independently by 11.58 (95% CI 2.16-21.01) cases per 1000 person-years. With higher LDL-C, we observe the CHD hazard rate attributable to the combined action of high hs-CRP and medium Lp-PLA was less than the sum of their individual effects by 13.42 (95% CI 2.44-24.40) cases per 1000 person-years. This demonstration serves the dual purposes of illustrating analysis techniques and providing insights about the utility of hs-CRP and Lp-PLA for identifying the high-risk population of CHD that the traditional risk factors such as the LDL-C may miss. Epidemiologists are encouraged to use this new tool to analyze other case-cohort studies and incorporate auxiliary variables embedded in the full cohort in their analysis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10654-021-00739-3DOI Listing
June 2021

Reply to Wilms tumor and breast cancer.

Cancer 2015 Jun 24;121(12):2099-100. Epub 2015 Feb 24.

Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.29278DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4503333PMC
June 2015

Z-estimation and stratified samples: application to survival models.

Lifetime Data Anal 2015 Oct 15;21(4):493-516. Epub 2015 Jan 15.

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

The infinite dimensional Z-estimation theorem offers a systematic approach to joint estimation of both Euclidean and non-Euclidean parameters in probability models for data. It is easily adapted for stratified sampling designs. This is important in applications to censored survival data because the inverse probability weights that modify the standard estimating equations often depend on the entire follow-up history. Since the weights are not predictable, they complicate the usual theory based on martingales. This paper considers joint estimation of regression coefficients and baseline hazard functions in the Cox proportional and Lin-Ying additive hazards models. Weighted likelihood equations are used for the former and weighted estimating equations for the latter. Regression coefficients and baseline hazards may be combined to estimate individual survival probabilities. Efficiency is improved by calibrating or estimating the weights using information available for all subjects. Although inefficient in comparison with likelihood inference for incomplete data, which is often difficult to implement, the approach provides consistent estimates of desired population parameters even under model misspecification.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10985-014-9317-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4503541PMC
October 2015

Breast cancer in female survivors of Wilms tumor: a report from the national Wilms tumor late effects study.

Cancer 2014 Dec 27;120(23):3722-30. Epub 2014 Oct 27.

Department of Biostatistics, University of Washington, Seattle, Washington.

Background: The standard treatment of pulmonary metastases in patients with Wilms tumor (WT) includes 12-gray radiotherapy (RT) to the entire chest. To the authors' knowledge, the risk of breast cancer (BC) in a large cohort of female survivors of WT has not previously been reported.

Methods: A total of 2492 female participants in National Wilms Tumor Studies 1 through 4 (1969-1995) were followed from age 15 years through the middle of 2013 for incident BC. The median age at the time of last contact was 27.3 years. The authors calculated cumulative risk at age 40 years (CR40), hazard ratios (HR) by Cox regression, standardized incidence ratios (SIRs) relative to US population rates, and 95% confidence intervals (95% CIs).

Results: The numbers of survivors with invasive BC divided by the numbers at risk were 16 of 369 (CR40, 14.8% [95% CI, 8.7-24.5]) for women who received chest RT for metastatic WT, 10 of 894 (CR40, 3.1% [95% CI, 1.3-7.41]) for those who received only abdominal RT, and 2 of 1229 (CR40, 0.3% [95% CI, 0.0-2.3]) for those who received no RT. The SIRs for these 3 groups were 27.6 (95% CI, 16.1-44.2) based on 5010 person-years (PY) of follow-up, 6.0 (95% CI, 2.9-11.0) based on 13,185 PY of follow-up, and 2.2 (95% CI, 0.3-7.8) based on 13,560 PY of follow-up, respectively. The risk was high regardless of the use of chest RT among women diagnosed with WT at age ≥10 years, with 9 of 90 women developing BC (CR40, 13.5% [95% CI, 5.6-30.6]; SIR, 23.6 [95% CI, 10.8-44.8] [PY, 1463]).

Conclusions: Female survivors of WT who were treated with chest RT had a high risk of developing early BC, with nearly 15% developing invasive disease by age 40 years. Current guidelines that recommend screening only those survivors who received ≥20 Gy of RT to the chest might be reevaluated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/cncr.28908DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4239191PMC
December 2014

Individual prediction of heart failure among childhood cancer survivors.

J Clin Oncol 2015 Feb 6;33(5):394-402. Epub 2014 Oct 6.

Eric J. Chow and Norman E. Breslow, Fred Hutchinson Cancer Research Center, Seattle Children's Hospital, University of Washington, Seattle, WA; Yan Chen and Yutaka Yasui, University of Alberta, Edmonton, Alberta, Canada; Leontien C. Kremer, Elizabeth A.M. Feijen, and Helena J. van der Pal, Emma Children's Hospital and Academic Medical Center, Amsterdam, the Netherlands; Melissa M. Hudson, Gregory T. Armstrong, Daniel M. Green, Daniel A. Mulrooney, Kirsten K. Ness, and Leslie L. Robison, St Jude Children's Research Hospital; Daniel A. Mulrooney, University of Tennessee, Memphis, TN; William L. Border and Lillian R. Meacham, Children's Healthcare of Atlanta, Emory University, Atlanta, GA; Kathleen A. Meeske, Children's Hospital of Los Angeles, University of Southern California, Los Angeles, CA; Kevin C. Oeffinger and Charles A. Sklar, Memorial Sloan-Kettering Cancer Center, New York, NY; and Marilyn Stovall and Rita E. Weathers, University of Texas MD Anderson Cancer Center, Houston, TX.

Purpose: To create clinically useful models that incorporate readily available demographic and cancer treatment characteristics to predict individual risk of heart failure among 5-year survivors of childhood cancer.

Patients And Methods: Survivors in the Childhood Cancer Survivor Study (CCSS) free of significant cardiovascular disease 5 years after cancer diagnosis (n = 13,060) were observed through age 40 years for the development of heart failure (ie, requiring medications or heart transplantation or leading to death). Siblings (n = 4,023) established the baseline population risk. An additional 3,421 survivors from Emma Children's Hospital (Amsterdam, the Netherlands), the National Wilms Tumor Study, and the St Jude Lifetime Cohort Study were used to validate the CCSS prediction models.

Results: Heart failure occurred in 285 CCSS participants. Risk scores based on selected exposures (sex, age at cancer diagnosis, and anthracycline and chest radiotherapy doses) achieved an area under the curve of 0.74 and concordance statistic of 0.76 at or through age 40 years. Validation cohort estimates ranged from 0.68 to 0.82. Risk scores were collapsed to form statistically distinct low-, moderate-, and high-risk groups, corresponding to cumulative incidences of heart failure at age 40 years of 0.5% (95% CI, 0.2% to 0.8%), 2.4% (95% CI, 1.8% to 3.0%), and 11.7% (95% CI, 8.8% to 14.5%), respectively. In comparison, siblings had a cumulative incidence of 0.3% (95% CI, 0.1% to 0.5%).

Conclusion: Using information available to clinicians soon after completion of childhood cancer therapy, individual risk for subsequent heart failure can be predicted with reasonable accuracy and discrimination. These validated models provide a framework on which to base future screening strategies and interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2014.56.1373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4314592PMC
February 2015

Using the Whole Cohort in the Analysis of Case-Control Data: Application to the Women's Health Initiative.

Stat Biosci 2013 Nov;5(2)

Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, MD, USA.

Standard analyses of data from case-control studies that are nested in a large cohort ignore information available for cohort members not sampled for the sub-study. This paper reviews several methods designed to increase estimation efficiency by using more of the data, treating the case-control sample as a two or three phase stratified sample. When applied to a study of coronary heart disease among women in the hormone trials of the Women's Health Initiative, modest but increasing gains in precision of regression coefficients were observed depending on the amount of cohort information used in the analysis. The gains were particularly evident for pseudo- or maximum likelihood estimates whose validity depends on the assumed model being correct. Larger standard errors were obtained for coefficients estimated by inverse probability weighted methods that are more robust to model misspecification. Such misspecification may have been responsible for an important difference in one key regression coefficient estimated using the weighted compared with the more efficient methods.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12561-013-9080-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3865808PMC
November 2013

Outcome of patients with Stage II/favorable histology Wilms tumor with and without local tumor spill: a report from the National Wilms Tumor Study Group.

Pediatr Blood Cancer 2014 Jan 23;61(1):134-9. Epub 2013 Aug 23.

Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: Intra-operative tumor spill increases the risk of local recurrence of Wilms tumor, and adversely impacts relapse-free (RFS) and overall survival (OS) rates.

Methods: Surgical checklists, operative notes, institutional pathology reports, central pathology review and flow sheets of 602 patients registered between August 1986 and September 1994 on National Wilms Tumor Study-4 as randomized, followed or switched and coded as Final Stage II, favorable histology (FH) were reviewed. RFS and OS were estimated using the Kaplan-Meier method. Hazard ratios (HRs) were estimated using the Cox model and tested for statistical significance by the log-rank test.

Results: Four hundred ninety-nine patients were found after review to have Stage II, FH Wilms tumor. The 8-year RFS percentages were 85.0% (95% confidence interval (CI): 81.1%, 88.1%) for those with no spill compared to 75.7% (65.8%, 83.2%) for those with spill. The 8-year OS percentages were 95.6% (93.1%, 97.3%) for those with no spill compared to 90.3% (82.2%, 94.9%) for those with spill. The HR for relapse among those with spill was 1.55 ((95%CI: 0.97,2.51), P = 0.067) and the HR for death was 1.94 ((0.92,4.09), P = 0.077).

Conclusions: RFS and OS were lower for patients who had intra-operative tumor spill. The majority of NWTS Stage II, FH patients with intra-operative tumor spill have an overall excellent outcome when treated with two drug chemotherapy (vincristine and actinomycin D) and no abdominal irradiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.24658DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933291PMC
January 2014

Pulmonary disease after treatment for Wilms tumor: a report from the national wilms tumor long-term follow-up study.

Pediatr Blood Cancer 2013 Oct 14;60(10):1721-6. Epub 2013 Jun 14.

Department of Epidemiology and Cancer Control, St. Jude Children's Research Hospital, Memphis, TN 38105-2794, USA.

Purpose: This study was undertaken to evaluate the incidence of pulmonary disease among patients treated with radiation therapy (RT) for pulmonary metastases (PM) from Wilms tumor (WT).

Patients And Methods: We reviewed records of 6,449 patients treated on National Wilms Tumor Studies-1, -2, -3, and -4 whose flow sheets or annual status reports documented one of several pulmonary conditions. Cases were fully evaluable if pulmonary function test (PFT) results were available, pulmonary fibrosis was identified on a chest radiograph or was listed as the primary or a contributing factor to death. Partially evaluable cases were those for whom PFT results could not be obtained. We evaluated the relationship between RT factors and the occurrence of pulmonary disease using hazard ratios (HRs) and cumulative incidence, treating death as a competing risk.

Results: Sixty-four fully evaluable and 16 partially evaluable cases of pulmonary disease were identified. The cumulative incidence of pulmonary disease at 15 years since WT diagnosis was 4.0% (95% confidence interval [CI] 2.6-5.4%) among fully evaluable and 4.8% (95% CI 3.3-6.4%) among fully and partially evaluable patients who received lung RT for PM at initial diagnosis. Rates of pulmonary disease were substantially higher among those who received lung RT for PM present at initial diagnosis or relapse compared to those who received no RT or only abdominal RT (HR 30.2, 95% CI 16.9-53.9).

Conclusion: The risk of pulmonary disease must be considered in evaluating the risk:benefit ratio of lung RT for the management of PM from WT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.24626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3933277PMC
October 2013

Clinicopathologic findings predictive of relapse in children with stage III favorable-histology Wilms tumor.

J Clin Oncol 2013 Mar 4;31(9):1196-201. Epub 2013 Feb 4.

University of Michigan, Ann Arbor, MI 48109, USA.

Purpose: Stage III designation in NWTS-5 (National Wilms Tumor Study-5) was determined by four pathologic criteria: positive lymph nodes (LNs), peritoneal implants, residual disease, and tumor rupture. The objective of this study was to determine the prognostic significance of each of the stage III criteria.

Patients And Methods: Children with stage III Wilms tumor (WT) treated in NWTS-5 were assessed for event-free (EFS) and overall survival (OS). Sites of relapse and molecular status of tumors are reported. EFS and OS are reported 8 years after diagnosis.

Results: There were 569 patients with local stage III favorable-histology (FH) WT in this analysis, of whom 109 had overall stage IV disease. LN involvement alone was the most frequent criterion for stage III designation (38%), followed by microscopic residual disease alone (20%), microscopic residual disease and LN involvement (14%), and spill or soilage alone (9%). The 8-year EFS and OS estimates for all patients with local stage III FHWT were 82% and 91%, respectively. Multivariate analysis demonstrated that both LN involvement (relative risk, 1.89; P = .005) and microscopic residual disease (relative risk, 1.87; P = .007) were predictive of EFS, and OS results were similar. There was no apparent difference in pattern of relapse according to stage III subtype. The rate of loss of heterozygosity was higher (6%) for those with positive LNs than for those without (2%; P = .05).

Conclusion: LN involvement and microscopic residual are the stage III criteria highly predictive of EFS and OS for patients with stage III FHWT. It is possible that in future studies, patients with different stage III criteria may receive different therapies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2011.41.1165DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595426PMC
March 2013

Treatments and outcomes for end-stage renal disease following Wilms tumor.

Pediatr Nephrol 2012 Aug 20;27(8):1325-33. Epub 2012 Mar 20.

Department of Biostatistics and Bioinformatics, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.

Background: Little is known about treatment outcomes for children who have end-stage renal disease (ESRD) after treatment for Wilms tumor (WT).

Methods: Time-to-transplant, graft failure, and survival outcomes were examined for 173 children enrolled on the National Wilms Tumor Study who developed ESRD.

Results: Fifty-five patients whose ESRD resulted from progressive bilateral WT (PBWT) experienced high early mortality from WT that limited their opportunity for transplant (47% at 5 years) and survival (44% at 10 years) in comparison to population controls. The 118 patients whose ESRD was due to other causes (termed "chronic kidney disease"), many of whom had WT-associated congenital anomalies, had transplant (77% at 5 years) and survival (73% at 10 years) outcomes no worse than those for population controls. Graft failure following transplant was comparable for the two groups. Minority children had twice the median time to transplant as non-Hispanic whites and twice the mortality rates, also reflecting population trends.

Conclusions: In view of the continuing high mortality in patients with ESRD, and the dramatic improvement in outlook following kidney transplantation, re-evaluation of current guidelines for a 2-year delay in transplant following WT treatment may be warranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s00467-012-2140-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3383943PMC
August 2012

Clinical significance of pulmonary nodules detected by CT and Not CXR in patients treated for favorable histology Wilms tumor on national Wilms tumor studies-4 and -5: a report from the Children's Oncology Group.

Pediatr Blood Cancer 2012 Oct 15;59(4):631-5. Epub 2012 Mar 15.

Department of Pediatrics and Oncology, University of Alberta, Edmonton Canada.

Background: Metastatic lung disease in Wilms tumor (WT) patients was traditionally identified by chest radiograph (CXR). It is unclear whether patients with small lesions, detectable only by computed tomography ("CT-only" lesions), require the more intensive therapy, including doxorubicin and lung irradiation, given to patients with metastases detectable by CXR.

Procedures: This study involved 417 patients with favorable histology WT and isolated lung metastases (detected by CXR or CT) who were registered on National Wilms tumor Study (NWTS)-4 or -5. Outcomes by method of detection (CXR vs. CT-only), use of lung radiation, and 2- or 3-drug chemotherapy (dactinomycin and vincristine ± doxorubicin) were determined and compared using the log-rank test.

Results: There were 231 patients with lung lesions detected by CXR and 186 by CT-only. Of the patients with CT-only nodules, 37 received only 2 drugs and 101 did not receive lung radiation. Five-year event-free survival (EFS) was greater for patients receiving three drugs (including doxorubicin) with or without lung radiation than for those receiving two drugs (80% vs. 56%; P = 0.004). There was no difference seen in 5-year overall survival (OS) between the 3- and 2-drug subsets (87% vs. 86%; P = 0.91). There were no significant differences in EFS (82% vs. 72%; P = 0.13) or OS (91% vs. 83%; P = 0.46) for patients with CT-only nodules whether they received lung radiation or not.

Conclusions: Our results suggest that patients with CT-only lung lesions may have improved EFS but not OS from the addition of doxorubicin but do not appear to benefit from pulmonary radiation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.24123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3397278PMC
October 2012

Risk factors for end stage renal disease in non-WT1-syndromic Wilms tumor.

J Urol 2011 Aug 17;186(2):378-86. Epub 2011 Jun 17.

Department of Biostatistics, University of Washington, Seattle, Washington 98112, USA.

Purpose: We assessed risk factors for end stage renal disease in patients with Wilms tumor without known WT1 related syndromes. We hypothesized that patients with characteristics suggestive of a WT1 etiology (early onset, stromal predominant histology, intralobar nephrogenic rests) would have a higher risk of end stage renal disease due to chronic renal failure. We predicted a high risk of end stage renal disease due to progressive bilateral Wilms tumor in patients with metachronous bilateral disease.

Materials And Methods: End stage renal disease was ascertained in 100 of 7,950 nonsyndromic patients enrolled in a National Wilms Tumor Study during 1969 to 2002. Risk factors were evaluated with cumulative incidence curves and proportional hazard regressions.

Results: The cumulative incidence of end stage renal disease due to chronic renal failure 20 years after Wilms tumor diagnosis was 0.7%. For end stage renal disease due to progressive bilateral Wilms tumor the incidence was 4.0% at 3 years after diagnosis in patients with synchronous bilateral Wilms tumor and 19.3% in those with metachronous bilateral Wilms tumor. For end stage renal disease due to chronic renal failure stromal predominant histology had a HR of 6.4 relative to mixed (95% CI 3.4, 11.9; p<0.001), intralobar rests had a HR of 5.9 relative to no rests (95% CI 2.0, 17.3; p=0.001), and Wilms tumor diagnosis at less than 24 months had a HR of 1.7 relative to 24 to 48 months and 2.8 relative to greater than 48 months (p=0.003 for trend).

Conclusions: Metachronous bilateral Wilms tumor is associated with high rates of end stage renal disease due to surgery for progressive Wilms tumor. Characteristics associated with a WT1 etiology markedly increased the risk of end stage renal disease due to chronic renal failure despite the low risk in non-WT1 syndromic cases overall.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.juro.2011.03.110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3133859PMC
August 2011

Commentary.

Authors:
Norman E Breslow

Biostatistics 2010 Jul;11(3):379-80

Department of Biostatistics, University of Washington, Seattle, WA 98195, USA,.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/biostatistics/kxq025DOI Listing
July 2010

Pregnancy outcome after treatment for Wilms tumor: a report from the national Wilms tumor long-term follow-up study.

J Clin Oncol 2010 Jun 10;28(17):2824-30. Epub 2010 May 10.

Department of Epidemiology and Cancer Control, St Jude Children's Research Hospital, 262 Danny Thomas Way, Mail Stop 735, Memphis, TN 38105-2794, USA.

Purpose: This study was undertaken to evaluate the effect of prior treatment with radiation therapy or chemotherapy for unilateral Wilms tumor (WT) diagnosed during childhood on pregnancy complications, birth weight, and the frequency of congenital malformations in live-born offspring.

Patients And Methods: We reviewed pregnancy outcomes among female survivors and partners of male survivors of WT treated on National Wilms Tumor Studies 1, 2, 3, and 4 by using a maternal questionnaire and a review of both maternal and offspring medical records.

Results: We received reports of 1,021 pregnancies with duration of 20 weeks or longer, including 955 live-born singletons, for whom 700 sets of maternal and offspring medical records were reviewed. Rates of hypertension complicating pregnancy (International Classification of Diseases [ICD] code 642), early or threatened labor (ICD-644) and malposition of the fetus (ICD-652) increased with increasing radiation dose in female patients. The percentages of offspring weighing less than 2,500 g at birth and of those having less than 37 weeks of gestation also increased with dose. There was no significant trend with radiation dose in the number of congenital anomalies recorded in offspring of female patients.

Conclusion: Women who receive flank radiation therapy as part of the treatment for unilateral WT are at increased risk of hypertension complicating pregnancy, fetal malposition, and premature labor. The offspring of these women are at risk for low birth weight and premature (ie, < 37 weeks gestation) birth. These risks must be considered in the obstetrical management of female survivors of WT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2009.27.2922DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903317PMC
June 2010

Improved Horvitz-Thompson Estimation of Model Parameters from Two-phase Stratified Samples: Applications in Epidemiology.

Stat Biosci 2009 May;1(1):32

Department of Biostatistics, University of Washington, Seattle, WA, USA, Tel.: +1-206-543-2035.

The case-cohort study involves two-phase sampling: simple random sampling from an infinite super-population at phase one and stratified random sampling from a finite cohort at phase two. Standard analyses of case-cohort data involve solution of inverse probability weighted (IPW) estimating equations, with weights determined by the known phase two sampling fractions. The variance of parameter estimates in (semi)parametric models, including the Cox model, is the sum of two terms: (i) the model based variance of the usual estimates that would be calculated if full data were available for the entire cohort; and (ii) the design based variance from IPW estimation of the unknown cohort total of the efficient influence function (IF) contributions. This second variance component may be reduced by adjusting the sampling weights, either by calibration to known cohort totals of auxiliary variables correlated with the IF contributions or by their estimation using these same auxiliary variables. Both adjustment methods are implemented in the R survey package. We derive the limit laws of coefficients estimated using adjusted weights. The asymptotic results suggest practical methods for construction of auxiliary variables that are evaluated by simulation of case-cohort samples from the National Wilms Tumor Study and by log-linear modeling of case-cohort data from the Atherosclerosis Risk in Communities Study. Although not semiparametric efficient, estimators based on adjusted weights may come close to achieving full efficiency within the class of augmented IPW estimators.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12561-009-9001-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2822363PMC
May 2009

Long-term outcomes for infants with very low risk Wilms tumor treated with surgery alone in National Wilms Tumor Study-5.

Ann Surg 2010 Mar;251(3):555-8

Department of Surgery, Children's Hospital Boston and Harvard Medical School, Boston, MA, USA.

Objective: To determine the event-free survival (EFS) and overall survival (OS) of children with very low risk Wilms tumor (VLRWT) treated with surgery only.

Background: Previous studies suggested that postoperative chemotherapy had not improved the prognosis of children with VLRWT. A total of 77 children <24 months of age with small (<550 g) Stage I favorable histology Wilms tumors were treated with surgery only. This study was closed based on stopping rules to ensure that the 2-year EFS was > or =90%.

Methods: A total of 77 children were assessed for EFS and OS. Of these patients, 21 enrolled at the time of closure were recalled, treated with dactinomycin and vincristine (regimen EE4A), and censored for analysis thereafter. About 111 children subsequently treated with EE4A were available for comparison.

Results: Median follow-up of surviving patients was 8.2 years for surgery only (range, 1.9-11.8 years) and 5.2 years for the EE4A group (range, 1.6-8.9 years). The estimated 5-year EFS for surgery only was 84% (95% confidence interval [CI]: 73%, 91%); for the EE4A patients it was 97% (95% CI: 92%, 99%, P = 0.002). One death was observed in each treatment group. The estimated 5-year OS was 98% (95% CI: 87%, 99%) for surgery only and 99% (95% CI: 94%, 99%) for EE4A (P = 0.70).

Conclusion: The surgery-only EFS was lower than anticipated but, coupled with a much higher than anticipated salvage rate of the chemotherapy naive patients whose disease recurred, led to an observed long-term OS equivalent to that seen with 2-drug chemotherapy. This approach to the treatment of patients with VLRWT eliminates the toxic side-effects of chemotherapy for a large majority of patients. A follow-up study is underway to confirm these findings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SLA.0b013e3181c0e5d7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836016PMC
March 2010

Secondary malignant neoplasms after Wilms tumor: an international collaborative study.

Int J Cancer 2010 Aug;127(3):657-66

Department of Biostatistics, University of Washington, Seattle, WA 98195-7232, USA.

A combined cohort of 8,884 North American, 2,893 British and 1,574 Nordic subjects with Wilms tumor (WT) diagnosed before 15 years of age during 1960-2004 was established to determine the risk of secondary malignant neoplasms (SMN). After 169,641 person-years (PY) of observation through 2005, 174 solid tumors (exclusive of basal cell carcinomas) and 28 leukemias were ascertained in 195 subjects. Median survival time after a solid SMN diagnosis 5 years or more from WT was 11 years; it was 10 months for all leukemia. Age-specific incidence of secondary solid tumors increased from approximately 1 case per 1,000 PY at age 15 to 5 cases per 1,000 PY at age 40. The cumulative incidence of solid tumors at age 40 for subjects who survived free of SMNs to age 15 was 6.7%. Leukemia risk, by contrast, was highest during the first 5 years after WT diagnosis. Standardized incidence ratios (SIRs) for solid tumors and leukemias were 5.1 and 5.0, respectively. Results for solid tumors for the 3 geographic areas were remarkably consistent; statistical tests for differences in incidence rates and SIRs were all negative. Age-specific incidence rates and SIRs for solid tumors were lower for patients whose WT was diagnosed after 1980, although the trends with decade of diagnosis were not statistically significant. Incidence rates and SIRs for leukemia were highest among those diagnosed after 1990 (p-trend = 0.003). These trends may reflect the decreasing use of radiation therapy and increasing intensity of chemotherapy in modern protocols for treatment of WT.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ijc.25067DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2878923PMC
August 2010

Portal hypertension in children with Wilms' tumor: a report from the National Wilms' Tumor Study Group.

Int J Radiat Oncol Biol Phys 2010 May 19;77(1):210-6. Epub 2009 Aug 19.

Department of Pediatrics, Medical College of Wisconsin, Milwaukee, Wisconsin 53326, USA.

Purpose: This analysis was undertaken to determine the cumulative risk of and risk factors for portal hypertension (PHTN) in patients with Wilms' tumor (WT).

Methods And Materials: Medical records were reviewed to identify cases of PHTN identified with late liver/spleen/gastric toxicities in a cohort of 5,195 patients treated with National Wilms' Tumor Studies (NWTS) protocols 1 to 4. A nested case control study (5 controls/case) was conducted to determine relationships among doxorubicin, radiation therapy (RT) dose to the liver, patient gender, and PHTN. Conditional logistic regression was used to estimate adjusted hazard ratios (HR) of PHTN associated with these factors.

Results: Cumulative risk of PHTN at 6 years from WT diagnosis was 0.7% for patients with right-sided tumors vs. 0.1% for those with left-sided tumors (p = 0.002). Seventeen of 19 cases were evaluable for RT. The majority of cases (16/17 [94%]) received right-flank RT either alone or as part of whole-abdomen RT and received >15 Gy to the liver. Fifteen of 17 (88%) patients received a higher dose to the liver than they would have with modern WT protocols. Controlling for RT dose, the HR was 3.0 for patients who received doxorubicin (p = 0.32) and 2.8 for females (p = 0.15). Controlling for doxorubicin, the 95% lower confidence bound on the HR associating PHTN with a minimum liver RT dose of >15 Gy vs. 15 Gy vs.
Conclusions: There was a strong association between higher doses of liver RT (>15 Gy) and the development of PHTN among WT patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2009.04.057DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888002PMC
May 2010

Intraoperative spillage of favorable histology wilms tumor cells: influence of irradiation and chemotherapy regimens on abdominal recurrence. A report from the National Wilms Tumor Study Group.

Int J Radiat Oncol Biol Phys 2010 Jan;76(1):201-6

Robert H. Lurie Cancer Center, Northwestern University, Chicago, IL, USA.

Purpose: We undertook this study to determine (1) the frequency with which spilled tumor cells of favorable histology produced intra-abdominal disease in patients treated with differing chemotherapy regimens and abdominal radiation therapy (RT) and (2) the patterns of relapse and outcomes in such patients.

Methods And Materials: The influence of RT dose (0, 10, and 20 Gy), RT fields (flank, whole abdomen), and chemotherapy with dactinomycin and vincristine (2 drugs) vs. added doxorubicin (three drugs) on intra-abdominal tumor recurrence rates was analyzed by logistic regression in 450 patients. Each patient was considered at risk for two types of failure: flank and subdiaphragmatic beyond-flank recurrence, with the correlation between the two outcomes accounted for in the analyses.

Results: The crude odds ratio for the risk of recurrence relative to no RT was 0.35 (0.15-0.78) for 10Gy and 0.08 (0.01-0.58) for 20Gy. The odds ratio for the risk of recurrence for doxorubicin to two drugs after adjusting for RT was not significant. For Stage II patients (NWTS-4), the 8-year event rates with and without spillage, respectively, were 79% and 87% for relapse-free survival (p = 0.07) and 90% and 95% for overall survival (p = 0.04).

Conclusions: Irradiation (10 Gy or 20 Gy) reduced abdominal tumor recurrence rates after tumor spillage. Tumor spillage in Stage II patients reduced relapse-free survival and overall survival, but only the latter was of statistical significance. These data provide a basis for assessing the risks vs. benefits when considering treatment for children with favorable histology Wilms tumor and surgical spillage.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.ijrobp.2009.01.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2843421PMC
January 2010

Using the whole cohort in the analysis of case-cohort data.

Am J Epidemiol 2009 Jun 8;169(11):1398-405. Epub 2009 Apr 8.

Department of Biostatistics, University of Washington, Seattle, Washington 98195-7232, USA.

Case-cohort data analyses often ignore valuable information on cohort members not sampled as cases or controls. The Atherosclerosis Risk in Communities (ARIC) study investigators, for example, typically report data for just the 10%-15% of subjects sampled for substudies of their cohort of 15,972 participants. Remaining subjects contribute to stratified sampling weights only. Analysis methods implemented in the freely available R statistical system (http://cran.r-project.org/) make better use of the data through adjustment of the sampling weights via calibration or estimation. By reanalyzing data from an ARIC study of coronary heart disease and simulations based on data from the National Wilms Tumor Study, the authors demonstrate that such adjustment can dramatically improve the precision of hazard ratios estimated for baseline covariates known for all subjects. Adjustment can also improve precision for partially missing covariates, those known for substudy participants only, when their values may be imputed with reasonable accuracy for the remaining cohort members. Links are provided to software, data sets, and tutorials showing in detail the steps needed to carry out the adjusted analyses. Epidemiologists are encouraged to consider use of these methods to enhance the accuracy of results reported from case-cohort analyses.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/aje/kwp055DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768499PMC
June 2009

Maternal exposure to medical radiation and Wilms tumor in the offspring: a report from the Children's Oncology Group.

Cancer Causes Control 2009 Aug 8;20(6):957-63. Epub 2009 Feb 8.

Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, PA 15213, USA.

Objective: This study examined the association between pre-conception and in utero maternal medical radiation exposure and Wilms tumor, using data from a large population-based case-control study.

Methods: Cases were identified from the National Wilms Tumor Study Group. Controls were identified by random digit dialing and frequency matched to child's age and geographic area of residence in the United States and Canada. Interview data from 512 cases and 509 controls were analyzed using multivariable logistic regression. Odds ratios (OR) and 95% confidence intervals (CI) for Wilms tumor and exposure to: (1) maternal X-ray alone and; (2) all medical radiation types (X-ray, CT, RT, Nuclear scans, Fluoroscopy) combined, for the period from two years before conception until child birth were estimated after adjustment for age, geographic area, maternal education, and household income.

Results: We found no consistent association between the risk of Wilms tumor and either maternal X-ray exposure (OR 0.9, 95% CI 0.7-1.3) or all medical radiation types combined (OR 0.9, 95% CI 0.7-1.2). No meaningful associations were seen for analysis of gonadal or non-gonadal radiation exposure.

Conclusion: Our study did not find any consistent pattern of association between Wilms tumor and maternal radiation exposure during pre-pregnancy or pregnancy period. In view of the negative findings from the largest case control study of this question to date, the reduced doses of biological radiation during pregnancy, and the requirements for an improved study design, we believe that future studies of this exposure may not be a priority for research on Wilms tumor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10552-009-9302-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2814068PMC
August 2009

Early and late mortality after diagnosis of wilms tumor.

J Clin Oncol 2009 Mar 12;27(8):1304-9. Epub 2009 Jan 12.

Department of Biostatistics, University of Washington, Mail Stop 357232, Seattle, WA 98195-7232, USA.

Purpose: To assess rates and causes of mortality in patients with Wilms tumor (WT).

Methods: Through 2002, 6,185 patients enrolled onto the National Wilms Tumor Study between 1969 and 1995 were actively observed. Deaths were classified on the basis of medical records as the result of original disease, late effects (including second malignant neoplasms [SMNs], cardiac causes, pulmonary disease, and renal failure), or other causes. Standardized mortality ratios (SMRs) and Cox regression were used to assess the effects of sex, age, and calendar period of diagnosis on mortality.

Results: Within 5 years of WT diagnosis, 819 deaths occurred, and 159 deaths occurred among 4,972 known 5-year survivors. The SMR was 24.3 (95% CI, 22.6 to 26.0) for the first 5 years, was 12.6 (95% CI, 10.0 to 15.7) for the next 5 years, and remained greater than 3.0 thereafter. For deaths in the first 5 years, the mortality risk decreased by 5-year calendar period of diagnosis (rate ratio [RR] = 0.78 per period). No such trend occurred for later deaths. Among 5-year survivors, 62 deaths were attributed to late effects of treatment or disease, including 27 to SMNs. A trend of decreased risk with calendar period of diagnosis was observed for late-effects mortality (RR = 0.86; 95% CI, 0.67 to 1.10) and for SMN mortality (RR = 0.82; 95% CI, 0.55 to 1.21).

Conclusion: Although the survival outlook for WT patients has improved greatly over time, survivors remain at elevated risk for death many years after their original diagnosis.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/JCO.2008.18.6981DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2667828PMC
March 2009

Anthropomorphic measurements and event-free survival in patients with favorable histology Wilms tumor: a report from the Children's Oncology Group.

Pediatr Blood Cancer 2009 Feb;52(2):254-8

IWK Health Centre, Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada.

Purpose: We retrospectively examined the effect of body weight and body mass index (BMI) on event-free survival (EFS) of children with Wilms tumor treated on National Wilms Tumor Study-5 (NWTS-5).

Patients And Methods: Eligible study participants: stages I-IV favorable histology Wilms tumor with immediate nephrectomy; height and weight recorded at diagnosis, and loss of heterozygosity for chromosomes 1p and 16q assessed.

Results: A total of 1,532 patients were included in the analysis. The median follow-up was 4.9 years. 493 patients were less than 2 years of age and 1039 were 2 years of age or older. In both age groups there were more patients than expected with a weight or body mass index (BMI) less than the 10 per thousand or greater than the 90 per thousand. There was no relationship of weight-for-age or BMI-for-age and EFS in univariate analyses (P = 0.28, log-rank test for both comparisons). A Cox proportional hazards model, stratified by risk/treatment groups, showed that, among patients less than 2 years of age, low or high weight-for-age was not predictive of EFS (P = 0.16). Similarly, a Cox proportional hazards model, stratified by risk/treatment groups, showed that among patients greater than 2 years of age, low or high body mass index for age was not predictive of EFS (P = 0.58).

Conclusions: There was no evidence that anthropomorphic data obtained at diagnosis for patients with favorable histology stages I-IV Wilms tumor was predictive for EFS in the setting of current treatment regimens. There were more patients with lower or higher weight/BMI than expected.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.21809DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2744809PMC
February 2009

Obstetric history and birth characteristics and Wilms tumor: a report from the Children's Oncology Group.

Cancer Causes Control 2008 Dec 29;19(10):1103-10. Epub 2008 May 29.

Department of Epidemiology, University of North Carolina, Chapel Hill, NC 27599-7435, USA.

Previous epidemiologic studies have suggested that various pregnancy and birth characteristics may be associated with Wilms tumor, a childhood kidney tumor. We evaluated obstetric events and birth characteristics in relation to Wilms tumor using data from a large North American case-control study. Mothers of 521 children with Wilms tumor and 517 controls, frequency matched on child's age and geographic region, provided information about their labor and delivery history and their children's birth characteristics through a detailed computer-assisted telephone interviews. Most obstetric factors were not associated with Wilms tumor, but modest associations were observed for labor induction (OR: 1.4, 95% Confidence Interval (CI): 1.1, 1.8), prenatal vaginal infection (OR: 1.8, 95% CI: 1.2, 2.8), and upper respiratory infection (OR: 1.5, 95% CI: 1.0, 2.4). Low (<2500 g) and high (>4500 g) birth weight and preterm delivery (<37 weeks completed gestation) were associated with an elevated risk of Wilms tumor, as was neonatal respiratory problems. The association for high birth weight was present only among children with perilobar nephrogenic rests (OR: 2.1, 95% CI: 1.2, 3.9), possibly distinguishing a specific association among a biologically distinct subgroup of Wilms tumor cases. The results of this large study did not support many of the earlier findings of smaller studies. However, additional investigations of the effects of certain obstetric and birth characteristics among more refined tumor subgroups may further our understanding of these factors in relation to Wilms tumor.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10552-008-9174-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2669650PMC
December 2008

A Z-theorem with Estimated Nuisance Parameters and Correction Note for 'Weighted Likelihood for Semiparametric Models and Two-phase Stratified Samples, with Application to Cox Regression'

Scand Stat Theory Appl 2008 Mar;35(1):186-192

Department of Biostatistics, University of Washington.

We state and prove a limit theorem for estimators of a general, possibly infinite dimensional parameter based on unbiased estimating equations containing estimated nuisance parameters. The theorem corrects a gap in the proof of one of the assertions of our paper 'Weighted likelihood for semiparametric models and two-phase stratified samples, with application to Cox regression'.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1467-9469.2007.00574.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2835417PMC
March 2008

Decreased core temperature and increased beta(3)-adrenergic sensitivity in diabetes-prone BB rats.

Diabetes Technol Ther 2007 Aug;9(4):354-62

Diabetes and Celiac Disease Unit, Department of Clinical Sciences, Lund University, Malmö, Sweden.

Background: Diabetes-prone (DP) congenic DR.lyp/lyp BioBreeding (BB) rats all develop Type 1 diabetes between 50 and 81 days of age, while DR.lyp/+ or DR.+/+ BB rats are diabetes resistant (DR). The DP rats display reduced weight gain prior to developing hyperglycemia, implying that metabolic events may precede diabetes onset. We tested the hypothesis that temperature measurements could serve as a physiological marker for the impending onset of hyperglycemia.

Methods: Prior to the onset of hyperglycemia, brain, lower back, and intrascapular brown adipose tissue temperatures were analyzed by thermal signature analysis, which measures infrared emission from tissues. A thermocoupled rectal probe measured core temperature. In addition we performed a beta(3)-adrenergic receptor challenge test with the beta(3)-adrenergic receptor agonist BRL37344.

Results: DP rats displayed lower core temperature than DR rats prior to the onset of hyperglycemia. No temperature difference was detected in brain, lower back, or intrascapular brown adipose tissue between DP and DR rats. The beta(3)-adrenergic challenge showed that the rate of temperature increase after administration of BRL37344 was significantly higher (0.005 +/- 0.002 degrees C/min) in DP than in DR rats (P = 0.044).

Conclusions: These studies reveal that the prediabetic DP rats fail to maintain core temperature and that they display increased sensitivity to heat production induced by a beta(3)-adrenergic receptor agonist. These studies suggest that body temperature as a measure of metabolic dysregulation is altered in the prediabetic DP rat prior to the onset of hyperglycemia.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/dia.2006.0036DOI Listing
August 2007

Mortality ascertainment of participants in the National Wilms Tumor Study using the National Death Index: comparison of active and passive follow-up results.

Epidemiol Perspect Innov 2007 Jul 2;4. Epub 2007 Jul 2.

Department of Biostatistics, University of Washington, Box 357232, Seattle, WA 98195, USA.

Long term studies of childhood cancer survivors are hampered by difficulties in tracking young adult participants. After performing a National Death Index (NDI) search we sought to identify which factors best predicted a match among known decedents from the National Wilms Tumor Study (NWTS) and to determine if record linkage could substitute for missing follow-up in a cohort of NWTS survivors. To our knowledge, this is the first study to compare passive mortality follow-up using the NDI to active follow-up of a childhood and young adult population. Records for 984 known decedents and 3,406 subjects whose January 1, 2002 vital status was unknown were sent to the NDI in June 2003. In April 2005 NWTS follow-up records were used to reassess January 1, 2002 vital status. Matches were established for 709 of 789 known decedents (sensitivity 89.9%) with a date of death between 1979 and 2001, the calendar period covered by the NDI at the time of the search. No matches were identified among 1,052 subjects known to be alive in 2002 (specificity 100%). Factors associated with decreased sensitivity were an unknown social security number (sensitivity 87.8%), Hispanic ethnicity (76.4%) and foreign birth (56.5%). For 2,351 subjects with 2002 vital status unknown who had 13,166 pre 2002 person-years of missing observation, only 18 deaths were ascertained by the NDI whereas 79.3 were expected based on NWTS mortality data. Mortality analyses based strictly on NDI search results and those based on NWTS follow-up augmented with NDI search results yielded inflated estimates of the 15 year survival rate when compared with estimates based on NWTS active follow-up. Match rates were comparable to those observed in adult populations. Since the same selection factors were likely associated with NDI failure to match and NWTS loss to follow-up, use of the NDI to fill in missing follow-up data appears unwarranted.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/1742-5573-4-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1934904PMC
July 2007

Treatment of Wilms tumor relapsing after initial treatment with vincristine, actinomycin D, and doxorubicin. A report from the National Wilms Tumor Study Group.

Pediatr Blood Cancer 2008 Feb;50(2):236-41

Department of Pediatrics, Children's Hospital Los Angeles, Los Angeles, California, USA.

Objective: We evaluated the use of alternating cycles of cyclophosphamide/etoposide and carboplatin/etoposide in children entered on National Wilms Tumor Study (NWTS)-5 who were diagnosed between August 1, 1995 and May 31, 2002 and who relapsed after chemotherapy with vincristine, actinomycin D, and doxorubicin (VAD) and radiation therapy (DD-4A).

Patients And Methods: One hundred three patients who relapsed or had progressive disease after initial VAD chemotherapy and radiation therapy were registered on stratum C of the NWTS-5 Relapse protocol. Twelve patients were not evaluable: five due to insufficient data, six due to major protocol violations, and one for refusal of therapy. Among the 91 remaining patients, 14 with stage V Wilms tumor (WT), 1 with contralateral relapse, and 16 who did not achieve a complete response (CR) to the initial three-drug chemotherapy were not included in this analysis. Relapse treatment included alternating courses of the drug pairs cyclophosphamide/etoposide and carboplatin/etoposide, surgery, and radiation therapy.

Results: The outcomes of 60 patients were analyzed. The lung was the only site of relapse for 33 patients; other sites of relapse included the operative bed, the abdomen, and liver. Four-year event-free survival (EFS) and overall survival (OS) were 42.3 and 48.0% respectively for all patients and were 48.9 and 52.8% for those who relapsed in the lungs only. Thrombocytopenia was the most frequent toxicity.

Conclusion: These results demonstrate that approximately one-half of children with unilateral WT who relapse after initial treatment with VAD and radiation therapy can be successfully retreated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.21267DOI Listing
February 2008

Renal failure does not preclude cure in children receiving chemotherapy for Wilms tumor: a report from the National Wilms Tumor Study Group.

Pediatr Blood Cancer 2008 Feb;50(2):242-5

Department of Hematology/Oncology, Children's Hospital & Research Center Oakland, Oakland, California, USA.

Background: Children with Wilms tumor can develop renal failure during treatment. Since there are few published data concerning the appropriate chemotherapy for this situation, we reviewed the experience of children who developed renal failure while being treated on National Wilms Tumor Study Group (NWTSG) studies 1-4 (1969-1994).

Patients And Methods: Data files in the NWTSG Data Center for all patients with Wilms tumor were screened. Patient demographics and tumor and treatment data were abstracted from those who developed renal failure.

Results: Twenty-eight of 5,910 (0.47%) children with Wilms tumor registered on NWTSG studies I through IV (1971-1994) were treated with chemotherapy after developing renal failure. Among these patients vincristine at full dose (0.05 mg/kg dose) did not increase the risk of severe toxicity. Dactinomycin (full dose: 15 mcg/kg day x 5) increased the risk for severe neutropenia when given at 75-100% of full dose. There was no compelling evidence for increased toxicity of doxorubicin when given at 100% versus 50% dosing (full dose: 20 mg/m(2) day x 3), but the number of patients analyzed was small. The overall survival percentage was 39%, but 64% for those patients who were in their initial treatment phase at the time of renal failure.

Conclusion: The data suggest that, in the setting of renal failure, reduction of dosing is not necessary for the three main agents used for treatment of newly diagnosed Wilms tumor, and cure is not precluded. Accurate pharmacologic and pharmacokinetic studies are needed for any patient being treated while in renal failure.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/pbc.21229DOI Listing
February 2008

Household pesticides and the risk of Wilms tumor.

Environ Health Perspect 2007 Jan;115(1):134-7

Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina 27599-7435, USA.

Background: Previous epidemiologic studies have suggested that exposure to pesticides in utero and during early childhood may increase the risk for development of childhood cancer, including Wilms tumor, a childhood kidney tumor.

Objectives: In this analysis we evaluated the role of residential pesticide exposure in relation to the risk of Wilms tumor in children using data from a North American case-control study.

Methods: The National Wilms Tumor Study Group (NWTSG) collected information on exposure to residential pesticides from the month before pregnancy through the diagnosis reference date using detailed phone interviews from 523 case mothers and 517 controls frequency matched on child's age and geographic region and identified by list-assisted random digit dialing. Pesticides were grouped according to type of pesticide and where they were used.

Results: A slightly increased risk of Wilms tumor was found among children of mothers who reported insecticide use [odds ratio (OR) = 1.4, 95% confidence interval (CI), 1.0-1.8; adjusted for education, income, and the matching variables]. Results from all other categories of pesticides were generally close to the null.

Conclusions: This study is the largest case-control study of Wilms tumor to date. We were unable to confirm earlier reports of an increased risk for Wilms tumor among those exposed to residential pesticides during pregnancy through early childhood.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1797847PMC
http://dx.doi.org/10.1289/ehp.9298DOI Listing
January 2007
-->