scholarly journals Loss of Heterozygosity at Chromosome 16q Is a Negative Prognostic Factor in Korean Pediatric Patients with Favorable Histology Wilms Tumor: A Report of the Korean Pediatric Hematology Oncology Group (K-PHOG)

2020 ◽  
Vol 52 (2) ◽  
pp. 438-445
Author(s):  
Jun Eun Park ◽  
O Kyu Noh ◽  
Yonghee Lee ◽  
Hyoung Soo Choi ◽  
Jung Woo Han ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Loss Of Heterozygosity ◽  
Prognostic Value ◽  
Wilms Tumor ◽  
Small Sample ◽  
Oncology Group ◽  
Korean Children ◽  
Pediatric Hematology ◽  
Favorable Histology ◽  
Negative Prognostic Factor

Purpose Loss of heterozygosity (LOH) at chromosomes 1p and 16q is a poor prognostic factor in favorable histology Wilms tumor (FHWT). This study investigated the prevalence of LOH at 1p and 16q and evaluated its prognostic value in Korean children with FHWT. Materials and Methods We analyzed 101 FHWT patients who were diagnosed between 1996 and 2016 in Korean Society of Pediatric Hematology Oncology Group hospitals. Using paraffin-embedded kidney tissue samples sent from each center, we reviewed LOH at 1p and 16q in each patient and assessed the prognostic value of LOH status for clinical parameters affecting event-free survival (EFS). Results Of the 101 patients, 12 (11.9%) experienced recurrence; the 3-year EFS was 87.6%. LOH at 1p or 16q was detected in 19 patients (18.8%), with five having LOH at both 1q and 16q. The frequency of LOH at 1p was higher among younger patients (p=0.049), but there was no difference in LOH prevalence according to tumor stage. In the multivariate analysis, LOH at 16q was a significant negative prognostic factor affecting EFS (3-year EFS, 73.7% vs. 91.1%; hazard ratio, 3.95; p=0.037), whereas LOH at 1p was not (p=0.786). Conclusion LOH at 16q was a significant negative prognostic factor affecting outcome in Korean pediatric FHWT patients. Due to the small sample size of this study, large-scale multicenter trials are warranted to investigate the prognostic value of LOH at 1p and 16q in Korean children with FHWT.

Augmentation of therapy for favorable-histology Wilms Tumor with combined loss of heterozygosity of chromosomes 1p and 16q: A report from the Children’s Oncology Group studies AREN0532 and AREN0533.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 10009-10009 ◽  
Author(s):  
David B. Dix ◽  
Conrad Vincent Fernandez ◽  
Yueh-Yun Chi ◽  
James Robert Anderson ◽  
Elizabeth Anne Mullen ◽  
...  
Keyword(s):  
Loss Of Heterozygosity ◽  
Wilms Tumor ◽  
Oncology Group ◽  
Favorable Histology

Loss of Heterozygosity for Chromosomes 1p and 16q Is an Adverse Prognostic Factor in Favorable-Histology Wilms Tumor: A Report From the National Wilms Tumor Study Group

2005 ◽  
Vol 23 (29) ◽  
pp. 7312-7321 ◽  
Author(s):  
Paul E. Grundy ◽  
Norman E. Breslow ◽  
Sierra Li ◽  
Elizabeth Perlman ◽  
J. Bruce Beckwith ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Loss Of Heterozygosity ◽  
Wilms Tumor ◽  
Clear Cell Sarcoma ◽  
Stage I ◽  
Disease Stage ◽  
Malignant Rhabdoid Tumor ◽  
Favorable Histology ◽  
Tumor Study ◽  
Increased Risk

Purpose To determine if tumor-specific loss of heterozygosity (LOH) for chromosomes 1p or 16q is associated with a poorer prognosis for children with favorable-histology (FH) Wilms tumor entered on the fifth National Wilms Tumor Study (NWTS-5). Patients and Methods Between August 1995 and June 2002, 2,021 previously untreated children with FH or anaplastic Wilms tumor, clear-cell sarcoma of the kidney (CCSK) or malignant rhabdoid tumor of the kidney (RTK), were treated with stage- and histology-specific therapy. Their tumors were assayed for LOH for polymorphic DNA markers on chromosomes 1p and 16q. Results LOH for 1p or 16q was rarely observed in CCSK (n = 90) or RTK (n = 22). The relative risk (RR) of relapse for patients with FH stage I to IV tumors with LOH, stratified by stage, was 1.56 for LOH 1p (P = .01) and 1.49 for LOH 16q (P = .01), whereas the RR of death was 1.84 (P = .03) and 1.44 (P = .15), respectively. When the effects of LOH for both regions were considered jointly among patients with stage I to II FH disease, the risks of relapse and death were increased for LOH 1p only (RR = 2.2, P = .02 for relapse; RR = 4.0, P = .02 for death), for LOH 16q only (RR = 1.9, P = .01 and RR = 1.4, P = .60) and for LOH for both regions (RR = 2.9, P = .001 and RR = 4.3, P = .01) in comparison with patients with LOH at neither locus. The risks of relapse and death for patients with stage III to IV FH tumors were increased only with LOH for both regions (RR = 2.4, P = .01 and RR = 2.7, P = .04). Conclusion Tumor-specific LOH for both chromosomes 1p and 16q identifies a subset of FH Wilms tumor patients who have a significantly increased risk of relapse and death. LOH for these chromosomal regions can now be used as an independent prognostic factor together with disease stage to target intensity of treatment to risk of treatment failure.

scholarly journals Predicting Relapse in Favorable Histology Wilms Tumor Using Gene Expression Analysis: A Report from the Renal Tumor Committee of the Children's Oncology Group

2009 ◽  
Vol 15 (5) ◽  
pp. 1770-1778 ◽  
Author(s):  
Chiang-Ching Huang ◽  
Samantha Gadd ◽  
Norman Breslow ◽  
Colleen Cutcliffe ◽  
Simone T. Sredni ◽  
...  
Keyword(s):  
Gene Expression ◽  
Expression Analysis ◽  
Gene Expression Analysis ◽  
Renal Tumor ◽  
Wilms Tumor ◽  
Oncology Group ◽  
Favorable Histology

scholarly journals Augmentation of Therapy for Combined Loss of Heterozygosity 1p and 16q in Favorable Histology Wilms Tumor: A Children’s Oncology Group AREN0532 and AREN0533 Study Report

2019 ◽  
Vol 37 (30) ◽  
pp. 2769-2777 ◽  
Author(s):  
David B. Dix ◽  
Conrad V. Fernandez ◽  
Yueh-Yun Chi ◽  
Elizabeth A. Mullen ◽  
James I. Geller ◽  
...  
Keyword(s):  
Overall Survival ◽  
Radiation Therapy ◽  
Loss Of Heterozygosity ◽  
Wilms Tumor ◽  
Adverse Outcomes ◽  
Stage I ◽  
Stage Iii ◽  
Rank Test ◽  
Favorable Histology ◽  
Grade 3

PURPOSE In National Wilms Tumor Study 5 (NWTS-5), tumor-specific combined loss of heterozygosity of chromosomes 1p and 16q (LOH1p/16q) was associated with adverse outcomes in patients with favorable histology Wilms tumor. The AREN0533/AREN0532 studies assessed whether augmenting therapy improved event-free survival (EFS) for these patients. Patients with stage I/II disease received regimen DD4A (vincristine, dactinomycin and doxorubicin) but no radiation therapy. Patients with stage III/IV disease received regimen M (vincristine, dactinomycin, and doxorubicin alternating with cyclophosphamide and etoposide) and radiation therapy. METHODS Patients were enrolled through the AREN03B2 Biology study between October 2006 and October 2013; all underwent central review of pathology, surgical reports, and imaging. Tumors were evaluated for LOH1p/16q by microsatellite testing. EFS and overall survival were compared using the log-rank test between NWTS-5 and current studies. RESULTS LOH1p/16q was detected in 49 of 1,147 evaluable patients with stage I/II disease (4.27%) enrolled in AREN03B2; 32 enrolled in AREN0532. LOH1p/16q was detected in 82 of 1,364 evaluable patients with stage III/IV disease (6.01%) in AREN03B2; 51 enrolled in AREN0533. Median follow-up for 83 eligible patients enrolled in AREN0532/0533 was 5.73 years (range, 2.84 to 9.63 years). The 4-year EFS for patients with stage I/II and stage III/IV disease with LOH1p/16 was 87.3% (95% CI, 75.1% to 99.5%) and 90.2% (95% CI, 81.8% to 98.6%), respectively. These results are improved compared with the NWTS-5 updated 4-year EFS of 68.8% for patients with stage I/II disease ( P = .042), and 61.3% for patients with stage III/IV disease ( P = .001), with trends toward improved 4-year overall survival. The most common grade 3 or higher nonhematologic toxicities with regimen M were febrile neutropenia (39.2%) and infections (21.6%). CONCLUSION Augmentation of therapy improved EFS for patients with favorable histology Wilms tumor and LOH1p/16q compared with the historical NWTS-5 comparison group, with an expected toxicity profile.

Older Age Is an Adverse Prognostic Factor in Stage I, Favorable Histology Wilms’ Tumor Treated With Vincristine Monochemotherapy: A Study by the United Kingdom Children’s Cancer Study Group, Wilm’s Tumor Working Group

2003 ◽  
Vol 21 (17) ◽  
pp. 3269-3275 ◽  
Author(s):  
K. Pritchard-Jones ◽  
A. Kelsey ◽  
G. Vujanic ◽  
J. Imeson ◽  
C. Hutton ◽  
...  
Keyword(s):  
United Kingdom ◽  
Prognostic Factor ◽  
Wilms Tumor ◽  
Stage I ◽  
Study Group ◽  
Cancer Study ◽  
Adverse Prognostic Factor ◽  
Favorable Histology ◽  
The United Kingdom ◽  
Cancer Study Group

Purpose: To identify clinical prognostic factors in children with stage I, favorable histology (FH) Wilms’ tumor treated with vincristine monochemotherapy after immediate nephrectomy to define subgroups for consideration of further reduction in treatment intensity. Patients and Methods: During two consecutive trials of the United Kingdom Children’s Cancer Study Group (UKW2 and UKW3, 1986 to 2001), 242 children with stage I FH Wilms’ tumor were treated with immediate nephrectomy followed by 10 weekly injections of vincristine 1.5 mg/m2. Event-free survival (EFS) and overall survival (OS) were compared by age group. Results: The 4-year EFS rate was 93.2%, 87.2%, and 71.3% for children less than 2 years old, 2 to 4 years old, and 4 years old or older at diagnosis, respectively (log-rank, P = .001); the corresponding 4-year OS rate was 98.1%, 95.0%, and 87.2% (log-rank, P = .01). There were no toxicity- or procedure-related deaths. In multivariate analysis, specimen weight was not of independent prognostic value (P = .66). Among the 186 children younger than 4 years at diagnosis, there were 17 relapses and five deaths, compared with 16 relapses and eight deaths among the 56 children at least 4 years old at diagnosis. OS after relapse was surprisingly poor (61.6% at 4 years). Conclusion: Treatment for stage I FH Wilms’ tumor is generally successful using vincristine monotherapy after immediate nephrectomy, and therefore, the risks of dactinomycin hepatopathy can be avoided. However, age at least 4 years is a significant adverse prognostic factor. This treatment schedule should be considered in any trial of treatment reduction in very young children with stage I FH Wilms’ tumor, regardless of tumor size, and we suggest that the upper age limit for the reduced therapy be set at 4 years.

Outcome and prognostic factors in stage III favorable histology Wilms tumor (FHWT): A report from the Children’s Oncology Group (COG) study AREN0532.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 10010-10010 ◽  
Author(s):  
Conrad Vincent Fernandez ◽  
Elizabeth Anne Mullen ◽  
Peter F. Ehrlich ◽  
John A. Kalapurakal ◽  
Geetika Khanna ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Wilms Tumor ◽  
Stage Iii ◽  
Oncology Group ◽  
Favorable Histology

Treatment of stage IV favorable histology Wilms tumor with incomplete lung metastasis response after chemotherapy: A report from Children’s Oncology Group study AREN0533.

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 10001-10001 ◽  
Author(s):  
David B. Dix ◽  
Eric J. Gratias ◽  
Nita Seibel ◽  
James Robert Anderson ◽  
Elizabeth Anne Mullen ◽  
...  
Keyword(s):  
Lung Metastasis ◽  
Wilms Tumor ◽  
Stage Iv ◽  
Oncology Group ◽  
Oncology Group Study ◽  
Favorable Histology
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