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. 2024 Mar 1;130(5):792-802.
doi: 10.1002/cncr.35084. Epub 2023 Oct 30.

Prognostic impact of lymph node involvement and loss of heterozygosity of 1p or 16q in stage III favorable histology Wilms tumor: A report from Children's Oncology Group Studies AREN03B2 and AREN0532

Affiliations

Prognostic impact of lymph node involvement and loss of heterozygosity of 1p or 16q in stage III favorable histology Wilms tumor: A report from Children's Oncology Group Studies AREN03B2 and AREN0532

Nicholas Evageliou et al. Cancer. .

Abstract

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.

Keywords: Wilms tumor; lymph node positivity; risk stratification; tumor genetics.

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Conflict of interest statement

Conflicts of Interest: None

Figures

Figure 1:
Figure 1:
Patient Selection Diagram
Figure 2:
Figure 2:
Overall EFS and OS
Figure 2:
Figure 2:
Overall EFS and OS
Figure 3:
Figure 3:
Univariate Effects of LN Status, LOH 1p, and LOH 16q on EFS
Figure 3:
Figure 3:
Univariate Effects of LN Status, LOH 1p, and LOH 16q on EFS
Figure 3:
Figure 3:
Univariate Effects of LN Status, LOH 1p, and LOH 16q on EFS
Figure 4:
Figure 4:
Combined Effects of LN Positivity with LOH 1p or LOH 16q on EFS and OS
Figure 4:
Figure 4:
Combined Effects of LN Positivity with LOH 1p or LOH 16q on EFS and OS
Figure 5:
Figure 5:
Combined Effect of LN Positivity with LOH of 1p or 16q on EFS and OS: 4 groups
Figure 5:
Figure 5:
Combined Effect of LN Positivity with LOH of 1p or 16q on EFS and OS: 4 groups

References

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