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.
N1 - Funding Information:
Supported by grants No. U10CA180886, U10CA180899, U10CA098543, U10CA098413, and U24CA114766 from the National Cancer Institute, National Institutes of Health, to support the Children’s Oncology Group. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Also supported by St Baldrick’s Foundation.
Publisher Copyright:
© 2018 American Society of Clinical Oncology.
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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U2 - 10.1200/JCO.2017.73.7999
DO - 10.1200/JCO.2017.73.7999
M3 - Article
C2 - 29211618
AN - SCOPUS:85040821736
SN - 0732-183X
VL - 36
SP - 254
EP - 261
JO - Journal of Clinical Oncology
JF - Journal of Clinical Oncology
IS - 3
ER -
