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; Lindsay A. Renfro; James Geller; Elizabeth Perlman; John Kalapurakal; Arnold Paulino; David Dix; Meryle J. Eklund; Andrew J. Murphy; Rodrigo L.P. Romao; Peter F. Ehrlich; Carly R. Varela; Kelly Vallance; Conrad V. Fernandez; Jeffrey S. Dome; Elizabeth A. Mullen

doi:10.1002/cncr.35084

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^*, Lindsay A. Renfro, James Geller, Elizabeth Perlman, John Kalapurakal, Arnold Paulino, David Dix, Meryle J. Eklund, Andrew J. Murphy, Rodrigo L.P. Romao, Peter F. Ehrlich, Carly R. Varela, Kelly Vallance, Conrad V. Fernandez, Jeffrey S. Dome, Elizabeth A. Mullen

^*Corresponding author for this work

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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.

Original language	English (US)
Pages (from-to)	792-802
Number of pages	11
Journal	cancer
Volume	130
Issue number	5
DOIs	https://doi.org/10.1002/cncr.35084
State	Published - Mar 1 2024

Funding

The authors thank the Children’s Oncology Group (COG) protocol coordinators, research coordinators, clinical research assistants, and other health professionals who contributed to acquiring samples used in this study. The authors in particular thank the extended AREN03B2 team who contributed to central review and clinical annotation of these samples. Very importantly, we are very grateful to the patients and their families for participating in these studies. Supported by grants U10CA180886, U10CA180899, U10CA098543, U10CA098413, and U24CA114766 from the National Cancer Institute, National Institutes of Health, to support the Children’s Oncology Group, and St. Baldrick’s Foundation.

Keywords

Wilms tumor
lymph node positivity
risk stratification
tumor genetics

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/cncr.35084

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Evageliou, N., Renfro, L. A., Geller, J., Perlman, E., Kalapurakal, J., Paulino, A., Dix, D., Eklund, M. J., Murphy, A. J., Romao, R. L. P., Ehrlich, P. F., Varela, C. R., Vallance, K., Fernandez, C. V., Dome, J. S., & Mullen, E. A. (2024). 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. cancer, 130(5), 792-802. https://doi.org/10.1002/cncr.35084

@article{76b150f3cb6842359f375193662644fc,

title = "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{\textquoteright}s Oncology Group Studies AREN03B2 and AREN0532",

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",

author = "Nicholas Evageliou and Renfro, {Lindsay A.} and James Geller and Elizabeth Perlman and John Kalapurakal and Arnold Paulino and David Dix and Eklund, {Meryle J.} and Murphy, {Andrew J.} and Romao, {Rodrigo L.P.} and Ehrlich, {Peter F.} and Varela, {Carly R.} and Kelly Vallance and Fernandez, {Conrad V.} and Dome, {Jeffrey S.} and Mullen, {Elizabeth A.}",

note = "Publisher Copyright: {\textcopyright} 2023 American Cancer Society.",

year = "2024",

month = mar,

day = "1",

doi = "10.1002/cncr.35084",

language = "English (US)",

volume = "130",

pages = "792--802",

journal = "cancer",

issn = "0008-543X",

publisher = "John Wiley and Sons Inc.",

number = "5",

}

Evageliou, N, Renfro, LA, Geller, J, Perlman, E, Kalapurakal, J, Paulino, A, Dix, D, Eklund, MJ, Murphy, AJ, Romao, RLP, Ehrlich, PF, Varela, CR, Vallance, K, Fernandez, CV, Dome, JS & Mullen, EA 2024, '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', cancer, vol. 130, no. 5, pp. 792-802. https://doi.org/10.1002/cncr.35084

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. / Evageliou, Nicholas; Renfro, Lindsay A.; Geller, James et al.
In: cancer, Vol. 130, No. 5, 01.03.2024, p. 792-802.

Research output: Contribution to journal › Article › peer-review

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.

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 - Wilms tumor

KW - lymph node positivity

KW - risk stratification

KW - tumor genetics

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UR - http://www.scopus.com/inward/citedby.url?scp=85175421250&partnerID=8YFLogxK

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 -

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

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