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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

Nicholas Evageliou  1 , Lindsay A Renfro  2 , James Geller  3 , Elizabeth Perlman  4 , John Kalapurakal  5 , Arnold Paulino  6 , David Dix  7 , Meryle J Eklund  8 , Andrew J Murphy  9 , Rodrigo L P Romao  10 , Peter F Ehrlich  11 , Carly R Varela  12   13   14 , Kelly Vallance  15 , Conrad V Fernandez  16 , Jeffrey S Dome  12   14 , Elizabeth A Mullen  17
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
See this image and copyright information in PMC

References

    1. Spreafico F, Fernandez CV, Brok J et al.: Wilms Tumour. Nature Reviews Disease Primers. 7:75, 2021 - PubMed
    1. Vallance K, Refro L, Evageliou N et al.: Impact of Biomarkers on Outcome in Stage I and II Low Risk Favorable Histology Wilms Tumors. A report From the Children’s Oncology Group AREN03B2 Protocol. oral abstract, SIOP World Congress, Barcelona, 2022
    1. Pan Z, He H Tang L et al.,: Loss of Heterozygosity on Chromosome 16q Increases Relapse Risk in Wilms’ Tumor: a Meta-analysis. Oncotarget Vol * (no. 39), 2017. - PMC - PubMed
    1. Cone EB, Dalton SS, Van Noord M et al.: Biomarkers for Wilms Tumor: A Systematic Review. Journal of Urology 196: 1530–1535, 2016 - PMC - PubMed
    1. Dix D, Fernandez CV, Chi YY et al.: Augmentation of Therapy for Combined Loss of Heterozygosity 1p and 16q in Favorable Histology Wilms Tumor: A Children’s Oncology Group AREN0532 and AREN0533 Study Report. J Clin Oncol 37: 2769–2777, 2019 - PMC - PubMed

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