TY - JOUR
T1 - Prognostic impact of lymph node involvement and loss of heterozygosity of 1p or 16q in stage III favorable histology Wilms tumor
T2 - A report from Children’s Oncology Group Studies AREN03B2 and AREN0532
AU - Evageliou, Nicholas
AU - Renfro, Lindsay A.
AU - Geller, James
AU - Perlman, Elizabeth
AU - Kalapurakal, John
AU - Paulino, Arnold
AU - Dix, David
AU - Eklund, Meryle J.
AU - Murphy, Andrew J.
AU - Romao, Rodrigo L.P.
AU - Ehrlich, Peter F.
AU - Varela, Carly R.
AU - Vallance, Kelly
AU - Fernandez, Conrad V.
AU - Dome, Jeffrey S.
AU - Mullen, Elizabeth A.
N1 - Publisher Copyright:
© 2023 American Cancer Society.
PY - 2024/3/1
Y1 - 2024/3/1
N2 - Introduction: The prognostic impact of positive lymph nodes (LN+) and/or singular loss of heterozygosity (LOH) of 1p or 16q were assessed in children with stage III favorable histology Wilms tumor (FHWT) enrolled on AREN0532 or AREN03B2 alone. Patients and Methods: A total of 635 stage III FHWT vincristine/dactinomycin/doxorubicin (DD4A)–treated patients met inclusion criteria. Event-free survival (EFS) and overall survival are reported overall and by LN sampling, LN status, LOH 1p, LOH 16q, and a combination of LN status and singular LOH. Patients with unknown or positive combined LOH of 1p and 16q status and AREN03B2-only patients with unknown outcomes or treatment other than DD4A were excluded. Results: EFS did not differ by study, supporting pooling. Lack of LN sampling (hazard ratio [HR], 2.12; p =.0037), LN positivity (HR, 2.78; p =.0002), LOH 1p (HR, 2.18; p =.0067), and LOH 16q (HR, 1.72; p =.042) were associated with worse EFS. Compared with patients with both LN– and LOH–, those with negative nodes but positive LOH 1p or 16q and those with LN+ but LOH– for 1p or 16q had significantly worse EFS (HR, 3.05 and 3.57, respectively). Patients positive for both LN and LOH had the worst EFS (HR, 6.33; overall group factor, p <.0001). Conclusion: Findings confirm LN+ status as an adverse prognostic factor amplified by presence of singular LOH 1p or 16q, supporting study of intensified therapy for patients with LN+ in combination with singular LOH in a prospective clinical trial.
AB - Introduction: The prognostic impact of positive lymph nodes (LN+) and/or singular loss of heterozygosity (LOH) of 1p or 16q were assessed in children with stage III favorable histology Wilms tumor (FHWT) enrolled on AREN0532 or AREN03B2 alone. Patients and Methods: A total of 635 stage III FHWT vincristine/dactinomycin/doxorubicin (DD4A)–treated patients met inclusion criteria. Event-free survival (EFS) and overall survival are reported overall and by LN sampling, LN status, LOH 1p, LOH 16q, and a combination of LN status and singular LOH. Patients with unknown or positive combined LOH of 1p and 16q status and AREN03B2-only patients with unknown outcomes or treatment other than DD4A were excluded. Results: EFS did not differ by study, supporting pooling. Lack of LN sampling (hazard ratio [HR], 2.12; p =.0037), LN positivity (HR, 2.78; p =.0002), LOH 1p (HR, 2.18; p =.0067), and LOH 16q (HR, 1.72; p =.042) were associated with worse EFS. Compared with patients with both LN– and LOH–, those with negative nodes but positive LOH 1p or 16q and those with LN+ but LOH– for 1p or 16q had significantly worse EFS (HR, 3.05 and 3.57, respectively). Patients positive for both LN and LOH had the worst EFS (HR, 6.33; overall group factor, p <.0001). Conclusion: Findings confirm LN+ status as an adverse prognostic factor amplified by presence of singular LOH 1p or 16q, supporting study of intensified therapy for patients with LN+ in combination with singular LOH in a prospective clinical trial.
KW - lymph node positivity
KW - risk stratification
KW - tumor genetics
KW - Wilms tumor
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U2 - 10.1002/cncr.35084
DO - 10.1002/cncr.35084
M3 - Article
C2 - 37902955
AN - SCOPUS:85175421250
SN - 0008-543X
VL - 130
SP - 792
EP - 802
JO - Cancer
JF - Cancer
IS - 5
ER -