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

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.

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

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.

Individual prediction of heart failure among childhood cancer survivors.

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.

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

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.

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.

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.

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

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.

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

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).

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

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.

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.

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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

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.

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.

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.

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

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.

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

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.

Early and late mortality after diagnosis of wilms tumor.

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.

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

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.

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

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.

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'.

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'.