Treatment of stage IV favorable histology wilms tumor with lung metastases: A report from the children's oncology group AREN0533 study

David B. Dix, Nita L. Seibel, Yueh Yun Chi, Geetika Khanna, Eric Gratias, James R. Anderson, Elizabeth A. Mullen, James I. Geller, John A. Kalapurakal, Arnold C. Paulino, Elizabeth J. Perlman, Peter F. Ehrlich, Marcio Malogolowkin, Julie M. Gastier-Foster, Elizabeth Wagner, Paul E. Grundy, Conrad V. Fernandez, Jeffrey S. Dome

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Abstract

Purpose The National Wilms Tumor Study (NWTS) treatment of favorable histology Wilms tumor with lung metastases was vincristine/dactinomycin/doxorubicin (DD4A) and lung radiation therapy (RT). The AREN0533 study applied a new risk stratification and treatment strategy to improve event-free survival (EFS) while reducing exposure to lung RT. Methods Patients with favorable histology Wilms tumor and isolated lung metastases showing complete lung nodule response (CR) after 6 weeks of DD4A continued receiving chemotherapy without lung RT. Patients with incomplete response (IR) or loss of heterozygosity at chromosomes 1p/16q received lung RT and four cycles of cyclophosphamide/etoposide in addition to DD4A drugs (Regimen M). AREN0533 was designed to preserve a 4-year EFS of 85% for lung nodule CR and improve 4-year EFS from 75% to 85% for lung nodule IR. Results Among 292 assessable patients, 133 had CR and 159 had IR. For patients with CR, 4-year EFS and overall survival (OS) estimates were 79.5% (95% CI, 71.2% to 87.8%) and 96.1% (95% CI, 92.1% to 100%), respectively. Expected versus observed event rates were 15% and 20.2% (P = .052), respectively. For patients with IR, 4-year EFS and OS estimates were 88.5% (95% CI, 81.8% to 95.3%) and 95.4% (95% CI, 90.9% to 99.8%), respectively. Expected versus observed event rates were 25% and 12.2% (P, .001), respectively. Overall, 4-year EFS and OS were 85.4% (95% CI, 80.5% to 90.2%) and 95.6% (95% CI, 92.8% to 98.4%) compared with 72.5% (95% CI, 66.9% to 78.1%; P <.001) and 84.0% (95% CI, 79.4% to 88.6%; P <.001), respectively, in the predecessor NWTS-5 study. Conclusion Excellent OS was achieved after omission of primary lung RT in patients with lung nodule CR, although there were more events than expected. EFS was significantly improved, with excellent OS, in patients with lung nodule IR using four cycles of cyclophosphamide/etoposide in addition to DD4A drugs. The overall AREN0533 treatment strategy yielded EFS and OS estimates that were superior to previous studies.

Original languageEnglish (US)
Pages (from-to)1564-1570
Number of pages7
JournalJournal of Clinical Oncology
Volume36
Issue number16
DOIs
StatePublished - Jun 1 2018

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Wilms Tumor
Histology
Neoplasm Metastasis
Lung
Disease-Free Survival
Radiotherapy
Survival
Therapeutics
Etoposide
Cyclophosphamide
Loss of Heterozygosity
Dactinomycin
Vincristine
Pharmaceutical Preparations
Doxorubicin
Chromosomes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Treatment of stage IV favorable histology wilms tumor with lung metastases : A report from the children's oncology group AREN0533 study. / Dix, David B.; Seibel, Nita L.; Chi, Yueh Yun; Khanna, Geetika; Gratias, Eric; Anderson, James R.; Mullen, Elizabeth A.; Geller, James I.; Kalapurakal, John A.; Paulino, Arnold C.; Perlman, Elizabeth J.; Ehrlich, Peter F.; Malogolowkin, Marcio; Gastier-Foster, Julie M.; Wagner, Elizabeth; Grundy, Paul E.; Fernandez, Conrad V.; Dome, Jeffrey S.

In: Journal of Clinical Oncology, Vol. 36, No. 16, 01.06.2018, p. 1564-1570.

Research output: Contribution to journalArticle

Dix, DB, Seibel, NL, Chi, YY, Khanna, G, Gratias, E, Anderson, JR, Mullen, EA, Geller, JI, Kalapurakal, JA, Paulino, AC, Perlman, EJ, Ehrlich, PF, Malogolowkin, M, Gastier-Foster, JM, Wagner, E, Grundy, PE, Fernandez, CV & Dome, JS 2018, 'Treatment of stage IV favorable histology wilms tumor with lung metastases: A report from the children's oncology group AREN0533 study', Journal of Clinical Oncology, vol. 36, no. 16, pp. 1564-1570. https://doi.org/10.1200/JCO.2017.77.1931
Dix, David B. ; Seibel, Nita L. ; Chi, Yueh Yun ; Khanna, Geetika ; Gratias, Eric ; Anderson, James R. ; Mullen, Elizabeth A. ; Geller, James I. ; Kalapurakal, John A. ; Paulino, Arnold C. ; Perlman, Elizabeth J. ; Ehrlich, Peter F. ; Malogolowkin, Marcio ; Gastier-Foster, Julie M. ; Wagner, Elizabeth ; Grundy, Paul E. ; Fernandez, Conrad V. ; Dome, Jeffrey S. / Treatment of stage IV favorable histology wilms tumor with lung metastases : A report from the children's oncology group AREN0533 study. In: Journal of Clinical Oncology. 2018 ; Vol. 36, No. 16. pp. 1564-1570.
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title = "Treatment of stage IV favorable histology wilms tumor with lung metastases: A report from the children's oncology group AREN0533 study",
abstract = "Purpose The National Wilms Tumor Study (NWTS) treatment of favorable histology Wilms tumor with lung metastases was vincristine/dactinomycin/doxorubicin (DD4A) and lung radiation therapy (RT). The AREN0533 study applied a new risk stratification and treatment strategy to improve event-free survival (EFS) while reducing exposure to lung RT. Methods Patients with favorable histology Wilms tumor and isolated lung metastases showing complete lung nodule response (CR) after 6 weeks of DD4A continued receiving chemotherapy without lung RT. Patients with incomplete response (IR) or loss of heterozygosity at chromosomes 1p/16q received lung RT and four cycles of cyclophosphamide/etoposide in addition to DD4A drugs (Regimen M). AREN0533 was designed to preserve a 4-year EFS of 85{\%} for lung nodule CR and improve 4-year EFS from 75{\%} to 85{\%} for lung nodule IR. Results Among 292 assessable patients, 133 had CR and 159 had IR. For patients with CR, 4-year EFS and overall survival (OS) estimates were 79.5{\%} (95{\%} CI, 71.2{\%} to 87.8{\%}) and 96.1{\%} (95{\%} CI, 92.1{\%} to 100{\%}), respectively. Expected versus observed event rates were 15{\%} and 20.2{\%} (P = .052), respectively. For patients with IR, 4-year EFS and OS estimates were 88.5{\%} (95{\%} CI, 81.8{\%} to 95.3{\%}) and 95.4{\%} (95{\%} CI, 90.9{\%} to 99.8{\%}), respectively. Expected versus observed event rates were 25{\%} and 12.2{\%} (P, .001), respectively. Overall, 4-year EFS and OS were 85.4{\%} (95{\%} CI, 80.5{\%} to 90.2{\%}) and 95.6{\%} (95{\%} CI, 92.8{\%} to 98.4{\%}) compared with 72.5{\%} (95{\%} CI, 66.9{\%} to 78.1{\%}; P <.001) and 84.0{\%} (95{\%} CI, 79.4{\%} to 88.6{\%}; P <.001), respectively, in the predecessor NWTS-5 study. Conclusion Excellent OS was achieved after omission of primary lung RT in patients with lung nodule CR, although there were more events than expected. EFS was significantly improved, with excellent OS, in patients with lung nodule IR using four cycles of cyclophosphamide/etoposide in addition to DD4A drugs. The overall AREN0533 treatment strategy yielded EFS and OS estimates that were superior to previous studies.",
author = "Dix, {David B.} and Seibel, {Nita L.} and Chi, {Yueh Yun} and Geetika Khanna and Eric Gratias and Anderson, {James R.} and Mullen, {Elizabeth A.} and Geller, {James I.} and Kalapurakal, {John A.} and Paulino, {Arnold C.} and Perlman, {Elizabeth J.} and Ehrlich, {Peter F.} and Marcio Malogolowkin and Gastier-Foster, {Julie M.} and Elizabeth Wagner and Grundy, {Paul E.} and Fernandez, {Conrad V.} and Dome, {Jeffrey S.}",
year = "2018",
month = "6",
day = "1",
doi = "10.1200/JCO.2017.77.1931",
language = "English (US)",
volume = "36",
pages = "1564--1570",
journal = "Journal of Clinical Oncology",
issn = "0732-183X",
publisher = "American Society of Clinical Oncology",
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TY - JOUR

T1 - Treatment of stage IV favorable histology wilms tumor with lung metastases

T2 - A report from the children's oncology group AREN0533 study

AU - Dix, David B.

AU - Seibel, Nita L.

AU - Chi, Yueh Yun

AU - Khanna, Geetika

AU - Gratias, Eric

AU - Anderson, James R.

AU - Mullen, Elizabeth A.

AU - Geller, James I.

AU - Kalapurakal, John A.

AU - Paulino, Arnold C.

AU - Perlman, Elizabeth J.

AU - Ehrlich, Peter F.

AU - Malogolowkin, Marcio

AU - Gastier-Foster, Julie M.

AU - Wagner, Elizabeth

AU - Grundy, Paul E.

AU - Fernandez, Conrad V.

AU - Dome, Jeffrey S.

PY - 2018/6/1

Y1 - 2018/6/1

N2 - Purpose The National Wilms Tumor Study (NWTS) treatment of favorable histology Wilms tumor with lung metastases was vincristine/dactinomycin/doxorubicin (DD4A) and lung radiation therapy (RT). The AREN0533 study applied a new risk stratification and treatment strategy to improve event-free survival (EFS) while reducing exposure to lung RT. Methods Patients with favorable histology Wilms tumor and isolated lung metastases showing complete lung nodule response (CR) after 6 weeks of DD4A continued receiving chemotherapy without lung RT. Patients with incomplete response (IR) or loss of heterozygosity at chromosomes 1p/16q received lung RT and four cycles of cyclophosphamide/etoposide in addition to DD4A drugs (Regimen M). AREN0533 was designed to preserve a 4-year EFS of 85% for lung nodule CR and improve 4-year EFS from 75% to 85% for lung nodule IR. Results Among 292 assessable patients, 133 had CR and 159 had IR. For patients with CR, 4-year EFS and overall survival (OS) estimates were 79.5% (95% CI, 71.2% to 87.8%) and 96.1% (95% CI, 92.1% to 100%), respectively. Expected versus observed event rates were 15% and 20.2% (P = .052), respectively. For patients with IR, 4-year EFS and OS estimates were 88.5% (95% CI, 81.8% to 95.3%) and 95.4% (95% CI, 90.9% to 99.8%), respectively. Expected versus observed event rates were 25% and 12.2% (P, .001), respectively. Overall, 4-year EFS and OS were 85.4% (95% CI, 80.5% to 90.2%) and 95.6% (95% CI, 92.8% to 98.4%) compared with 72.5% (95% CI, 66.9% to 78.1%; P <.001) and 84.0% (95% CI, 79.4% to 88.6%; P <.001), respectively, in the predecessor NWTS-5 study. Conclusion Excellent OS was achieved after omission of primary lung RT in patients with lung nodule CR, although there were more events than expected. EFS was significantly improved, with excellent OS, in patients with lung nodule IR using four cycles of cyclophosphamide/etoposide in addition to DD4A drugs. The overall AREN0533 treatment strategy yielded EFS and OS estimates that were superior to previous studies.

AB - Purpose The National Wilms Tumor Study (NWTS) treatment of favorable histology Wilms tumor with lung metastases was vincristine/dactinomycin/doxorubicin (DD4A) and lung radiation therapy (RT). The AREN0533 study applied a new risk stratification and treatment strategy to improve event-free survival (EFS) while reducing exposure to lung RT. Methods Patients with favorable histology Wilms tumor and isolated lung metastases showing complete lung nodule response (CR) after 6 weeks of DD4A continued receiving chemotherapy without lung RT. Patients with incomplete response (IR) or loss of heterozygosity at chromosomes 1p/16q received lung RT and four cycles of cyclophosphamide/etoposide in addition to DD4A drugs (Regimen M). AREN0533 was designed to preserve a 4-year EFS of 85% for lung nodule CR and improve 4-year EFS from 75% to 85% for lung nodule IR. Results Among 292 assessable patients, 133 had CR and 159 had IR. For patients with CR, 4-year EFS and overall survival (OS) estimates were 79.5% (95% CI, 71.2% to 87.8%) and 96.1% (95% CI, 92.1% to 100%), respectively. Expected versus observed event rates were 15% and 20.2% (P = .052), respectively. For patients with IR, 4-year EFS and OS estimates were 88.5% (95% CI, 81.8% to 95.3%) and 95.4% (95% CI, 90.9% to 99.8%), respectively. Expected versus observed event rates were 25% and 12.2% (P, .001), respectively. Overall, 4-year EFS and OS were 85.4% (95% CI, 80.5% to 90.2%) and 95.6% (95% CI, 92.8% to 98.4%) compared with 72.5% (95% CI, 66.9% to 78.1%; P <.001) and 84.0% (95% CI, 79.4% to 88.6%; P <.001), respectively, in the predecessor NWTS-5 study. Conclusion Excellent OS was achieved after omission of primary lung RT in patients with lung nodule CR, although there were more events than expected. EFS was significantly improved, with excellent OS, in patients with lung nodule IR using four cycles of cyclophosphamide/etoposide in addition to DD4A drugs. The overall AREN0533 treatment strategy yielded EFS and OS estimates that were superior to previous studies.

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