Outcome and prognostic factors in stage III favorable-Histology wilms tumor

A report from the children’s oncology group study AREN0532

Conrad V. Fernandez, Elizabeth A. Mullen, Yueh Yun Chi, Peter F. Ehrlich, Elizabeth J. Perlman, John A. Kalapurakal, Geetika Khanna, Arnold C. Paulino, Thomas E. Hamilton, Kenneth W. Gow, Zelig Tochner, Fredric A. Hoffer, Janice S. Withycombe, Robert C. Shamberger, Yeonil Kim, James I. Geller, James R. Anderson, Paul E. Grundy, Jeffrey S. Dome

Research output: Contribution to journalArticle

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Abstract

Background The National Wilms Tumor Study (NWTS) approach to treating stage III favorable-histology Wilms tumor (FHWT) is Regimen DD4A (vincristine, dactinomycin, and doxorubicin) and radiation therapy. Further risk stratification is required to improve outcomes and reduce late effects. We evaluated clinical and biologic variables for patients with stage III FHWT without combined loss of heterozygosity (LOH) at chromosomes 1p and 16q treated in the Children’s Oncology Group protocol AREN0532. Methods From October 2006 to August 2013, 588 prospectively treated, centrally reviewed patients with stage III FHWT were treated with Regimen DD4A and radiation therapy. Tumor LOH at 1p and 16q was determined by microsatellite analysis. Ineligible patients (n = 5) and those with combined LOH 1p/16q (n = 40) were excluded. Results A total of 535 patients with stage III disease were studied. Median follow-up was 5.2 years (range, 0.2 to 9.5). Four-year event-free survival (EFS) and overall survival estimates were 88% (95% CI, 85% to 91%) and 97% (95% CI, 95% to 99%), respectively. A total of 58 of 66 relapses occurred in the first 2 years, predominantly pulmonary (n = 36). Eighteen patients died, 14 secondary to disease. A better EFS was associated with negative lymph node status (P, .01) and absence of LOH 1p or 16q (P, .01), but not with gross residual disease or peritoneal implants. In contrast, the 4-year EFS was only 74% in patients with combined positive lymph node status and LOH 1p or 16q. A total of 123 patients (23%) had delayed nephrectomy. Submitted delayed nephrectomy histology showed anaplasia (n = 8; excluded from survival analysis); low risk/completely necrotic (n = 7; zero relapses), intermediate risk (n = 63; six relapses), and high-risk/blastemal type (n=7; five relapses). Conclusion Most patients with stage III FHWT had good EFS/overall survival with DD4A and radiation therapy. Combined lymph node and LOH status was highly predictive of EFS and should be considered as a potential prognostic marker for future trials.

Original languageEnglish (US)
Pages (from-to)254-261
Number of pages8
JournalJournal of Clinical Oncology
Volume36
Issue number3
DOIs
StatePublished - Jan 20 2018

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Wilms Tumor
Loss of Heterozygosity
Histology
Disease-Free Survival
Recurrence
Radiotherapy
Lymph Nodes
Nephrectomy
Peritoneal Diseases
Anaplasia
Survival
Dactinomycin
Vincristine
Survival Analysis
Microsatellite Repeats
Doxorubicin
Chromosomes
Lung

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Fernandez, Conrad V. ; Mullen, Elizabeth A. ; Chi, Yueh Yun ; Ehrlich, Peter F. ; Perlman, Elizabeth J. ; Kalapurakal, John A. ; Khanna, Geetika ; Paulino, Arnold C. ; Hamilton, Thomas E. ; Gow, Kenneth W. ; Tochner, Zelig ; Hoffer, Fredric A. ; Withycombe, Janice S. ; Shamberger, Robert C. ; Kim, Yeonil ; Geller, James I. ; Anderson, James R. ; Grundy, Paul E. ; Dome, Jeffrey S. / Outcome and prognostic factors in stage III favorable-Histology wilms tumor : A report from the children’s oncology group study AREN0532. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 3. pp. 254-261.
@article{3315392cb8aa4e05bd2f550c07133293,
title = "Outcome and prognostic factors in stage III favorable-Histology wilms tumor: A report from the children’s oncology group study AREN0532",
abstract = "Background The National Wilms Tumor Study (NWTS) approach to treating stage III favorable-histology Wilms tumor (FHWT) is Regimen DD4A (vincristine, dactinomycin, and doxorubicin) and radiation therapy. Further risk stratification is required to improve outcomes and reduce late effects. We evaluated clinical and biologic variables for patients with stage III FHWT without combined loss of heterozygosity (LOH) at chromosomes 1p and 16q treated in the Children’s Oncology Group protocol AREN0532. Methods From October 2006 to August 2013, 588 prospectively treated, centrally reviewed patients with stage III FHWT were treated with Regimen DD4A and radiation therapy. Tumor LOH at 1p and 16q was determined by microsatellite analysis. Ineligible patients (n = 5) and those with combined LOH 1p/16q (n = 40) were excluded. Results A total of 535 patients with stage III disease were studied. Median follow-up was 5.2 years (range, 0.2 to 9.5). Four-year event-free survival (EFS) and overall survival estimates were 88{\%} (95{\%} CI, 85{\%} to 91{\%}) and 97{\%} (95{\%} CI, 95{\%} to 99{\%}), respectively. A total of 58 of 66 relapses occurred in the first 2 years, predominantly pulmonary (n = 36). Eighteen patients died, 14 secondary to disease. A better EFS was associated with negative lymph node status (P, .01) and absence of LOH 1p or 16q (P, .01), but not with gross residual disease or peritoneal implants. In contrast, the 4-year EFS was only 74{\%} in patients with combined positive lymph node status and LOH 1p or 16q. A total of 123 patients (23{\%}) had delayed nephrectomy. Submitted delayed nephrectomy histology showed anaplasia (n = 8; excluded from survival analysis); low risk/completely necrotic (n = 7; zero relapses), intermediate risk (n = 63; six relapses), and high-risk/blastemal type (n=7; five relapses). Conclusion Most patients with stage III FHWT had good EFS/overall survival with DD4A and radiation therapy. Combined lymph node and LOH status was highly predictive of EFS and should be considered as a potential prognostic marker for future trials.",
author = "Fernandez, {Conrad V.} and Mullen, {Elizabeth A.} and Chi, {Yueh Yun} and Ehrlich, {Peter F.} and Perlman, {Elizabeth J.} and Kalapurakal, {John A.} and Geetika Khanna and Paulino, {Arnold C.} and Hamilton, {Thomas E.} and Gow, {Kenneth W.} and Zelig Tochner and Hoffer, {Fredric A.} and Withycombe, {Janice S.} and Shamberger, {Robert C.} and Yeonil Kim and Geller, {James I.} and Anderson, {James R.} and Grundy, {Paul E.} and Dome, {Jeffrey S.}",
year = "2018",
month = "1",
day = "20",
doi = "10.1200/JCO.2017.73.7999",
language = "English (US)",
volume = "36",
pages = "254--261",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
number = "3",

}

Fernandez, CV, Mullen, EA, Chi, YY, Ehrlich, PF, Perlman, EJ, Kalapurakal, JA, Khanna, G, Paulino, AC, Hamilton, TE, Gow, KW, Tochner, Z, Hoffer, FA, Withycombe, JS, Shamberger, RC, Kim, Y, Geller, JI, Anderson, JR, Grundy, PE & Dome, JS 2018, 'Outcome and prognostic factors in stage III favorable-Histology wilms tumor: A report from the children’s oncology group study AREN0532', Journal of Clinical Oncology, vol. 36, no. 3, pp. 254-261. https://doi.org/10.1200/JCO.2017.73.7999

Outcome and prognostic factors in stage III favorable-Histology wilms tumor : A report from the children’s oncology group study AREN0532. / Fernandez, Conrad V.; Mullen, Elizabeth A.; Chi, Yueh Yun; Ehrlich, Peter F.; Perlman, Elizabeth J.; Kalapurakal, John A.; Khanna, Geetika; Paulino, Arnold C.; Hamilton, Thomas E.; Gow, Kenneth W.; Tochner, Zelig; Hoffer, Fredric A.; Withycombe, Janice S.; Shamberger, Robert C.; Kim, Yeonil; Geller, James I.; Anderson, James R.; Grundy, Paul E.; Dome, Jeffrey S.

In: Journal of Clinical Oncology, Vol. 36, No. 3, 20.01.2018, p. 254-261.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Outcome and prognostic factors in stage III favorable-Histology wilms tumor

T2 - A report from the children’s oncology group study AREN0532

AU - Fernandez, Conrad V.

AU - Mullen, Elizabeth A.

AU - Chi, Yueh Yun

AU - Ehrlich, Peter F.

AU - Perlman, Elizabeth J.

AU - Kalapurakal, John A.

AU - Khanna, Geetika

AU - Paulino, Arnold C.

AU - Hamilton, Thomas E.

AU - Gow, Kenneth W.

AU - Tochner, Zelig

AU - Hoffer, Fredric A.

AU - Withycombe, Janice S.

AU - Shamberger, Robert C.

AU - Kim, Yeonil

AU - Geller, James I.

AU - Anderson, James R.

AU - Grundy, Paul E.

AU - Dome, Jeffrey S.

PY - 2018/1/20

Y1 - 2018/1/20

N2 - Background The National Wilms Tumor Study (NWTS) approach to treating stage III favorable-histology Wilms tumor (FHWT) is Regimen DD4A (vincristine, dactinomycin, and doxorubicin) and radiation therapy. Further risk stratification is required to improve outcomes and reduce late effects. We evaluated clinical and biologic variables for patients with stage III FHWT without combined loss of heterozygosity (LOH) at chromosomes 1p and 16q treated in the Children’s Oncology Group protocol AREN0532. Methods From October 2006 to August 2013, 588 prospectively treated, centrally reviewed patients with stage III FHWT were treated with Regimen DD4A and radiation therapy. Tumor LOH at 1p and 16q was determined by microsatellite analysis. Ineligible patients (n = 5) and those with combined LOH 1p/16q (n = 40) were excluded. Results A total of 535 patients with stage III disease were studied. Median follow-up was 5.2 years (range, 0.2 to 9.5). Four-year event-free survival (EFS) and overall survival estimates were 88% (95% CI, 85% to 91%) and 97% (95% CI, 95% to 99%), respectively. A total of 58 of 66 relapses occurred in the first 2 years, predominantly pulmonary (n = 36). Eighteen patients died, 14 secondary to disease. A better EFS was associated with negative lymph node status (P, .01) and absence of LOH 1p or 16q (P, .01), but not with gross residual disease or peritoneal implants. In contrast, the 4-year EFS was only 74% in patients with combined positive lymph node status and LOH 1p or 16q. A total of 123 patients (23%) had delayed nephrectomy. Submitted delayed nephrectomy histology showed anaplasia (n = 8; excluded from survival analysis); low risk/completely necrotic (n = 7; zero relapses), intermediate risk (n = 63; six relapses), and high-risk/blastemal type (n=7; five relapses). Conclusion Most patients with stage III FHWT had good EFS/overall survival with DD4A and radiation therapy. Combined lymph node and LOH status was highly predictive of EFS and should be considered as a potential prognostic marker for future trials.

AB - Background The National Wilms Tumor Study (NWTS) approach to treating stage III favorable-histology Wilms tumor (FHWT) is Regimen DD4A (vincristine, dactinomycin, and doxorubicin) and radiation therapy. Further risk stratification is required to improve outcomes and reduce late effects. We evaluated clinical and biologic variables for patients with stage III FHWT without combined loss of heterozygosity (LOH) at chromosomes 1p and 16q treated in the Children’s Oncology Group protocol AREN0532. Methods From October 2006 to August 2013, 588 prospectively treated, centrally reviewed patients with stage III FHWT were treated with Regimen DD4A and radiation therapy. Tumor LOH at 1p and 16q was determined by microsatellite analysis. Ineligible patients (n = 5) and those with combined LOH 1p/16q (n = 40) were excluded. Results A total of 535 patients with stage III disease were studied. Median follow-up was 5.2 years (range, 0.2 to 9.5). Four-year event-free survival (EFS) and overall survival estimates were 88% (95% CI, 85% to 91%) and 97% (95% CI, 95% to 99%), respectively. A total of 58 of 66 relapses occurred in the first 2 years, predominantly pulmonary (n = 36). Eighteen patients died, 14 secondary to disease. A better EFS was associated with negative lymph node status (P, .01) and absence of LOH 1p or 16q (P, .01), but not with gross residual disease or peritoneal implants. In contrast, the 4-year EFS was only 74% in patients with combined positive lymph node status and LOH 1p or 16q. A total of 123 patients (23%) had delayed nephrectomy. Submitted delayed nephrectomy histology showed anaplasia (n = 8; excluded from survival analysis); low risk/completely necrotic (n = 7; zero relapses), intermediate risk (n = 63; six relapses), and high-risk/blastemal type (n=7; five relapses). Conclusion Most patients with stage III FHWT had good EFS/overall survival with DD4A and radiation therapy. Combined lymph node and LOH status was highly predictive of EFS and should be considered as a potential prognostic marker for future trials.

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DO - 10.1200/JCO.2017.73.7999

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SP - 254

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JO - Journal of Clinical Oncology

JF - Journal of Clinical Oncology

SN - 0732-183X

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