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. 2021 Jan:143:127-133.
doi: 10.1016/j.ejca.2020.10.018. Epub 2020 Dec 7.

The prognostic significance of anaplasia in childhood rhabdomyosarcoma: A report from the Children's Oncology Group

Archana Shenoy  1 , Elysia Alvarez  2 , Yueh-Yun Chi  3 , Minjie Li  4 , Jack F Shern  5 , Javed Khan  5 , Susan M Hiniker  6 , Candace F Granberg  7 , Douglas S Hawkins  8 , David M Parham  9 , Lisa A Teot  10 , Erin R Rudzinski  8
Affiliations

The prognostic significance of anaplasia in childhood rhabdomyosarcoma: A report from the Children's Oncology Group

Archana Shenoy et al. Eur J Cancer. 2021 Jan.

Abstract

Background: Established prognostic indicators in rhabdomyosarcoma (RMS), the most common childhood soft tissue sarcoma, include several clinicopathologic features. Among pathologic features, anaplasia has been suggested as a potential prognostic indicator, but the clinical significance of anaplasia remains unclear.

Methods: Patients enrolled on one of five recent Children's Oncology Group clinical trials for RMS (D9602, n = 357; D9802, n = 80; D9803, n = 462; ARST0331, n = 335; and ARST0531, n = 414) with prospective central pathology review were included in this study. Clinicopathologic variables including demographic information, risk group, histologic subtype, and anaplasia were recorded along with overall survival (OS) and failure-free survival (FFS) with failure defined by recurrence, progression, or death. The log-rank test was used to compare OS and FFS.

Results: Anaplasia was more common in embryonal RMS (27% of all embryonal RMS) than other subtypes of RMS (11% for alveolar RMS, 7% for botryoid RMS, 11% for spindle cell RMS). On multivariate analyses, anaplasia was not an independent prognostic factor in RMS (OS:hazard ratio (HR) = 1.12, p = 0.43; FFS:HR = 1.07, p = 0.56) across all subtypes or within embryonal RMS only (OS:HR = 1.41, p = 0.078; FFS:HR = 1.25, p = 0.16). Among tumors with TP53 mutations, 69% had anaplasia, while only 24% of tumors with anaplasia had a tumoral TP53 mutation.

Conclusions: Anaplasia is not an independent indicator of adverse outcomes in RMS. Emerging information on the prognostic significance of TP53 mutations raises the possibility that anaplasia may be a surrogate marker of TP53 mutations in some cases. Tumoral TP53 mutation status may be investigated as a prognostic indicator in future studies.

Keywords: Anaplasia; Rhabdomyosarcoma; TP53 genes.

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Conflict of interest statement

Conflict of interest statement Douglas S Hawkins has the following disclosures: Loxo Oncology, Bayer, Bristol Myers Squibb, Lilly: Clinical trial fees paid to Seattle Children's to offset costs of study conduct; reimbursed for or provided travel, housing, and food to attend medial advisory board meetings; Celgene: Reimbursed for or provided travel, housing, and food to attend medial advisory board meetings, Eisai, Glaxo Smith Kline, Sanofi, Novartis, Amgen, Seattle Genetics, Jazz Pharmaceuticals, Incyte: Clinical trial fees paid to Seattle Children's to offset costs of study conduct. All other authors have no disclosures.

Figures

Figure 1:
Figure 1:
Failure Free Survival in All Patients with Rhabdomyosarcoma by Anaplasia Status
Figure 2:
Figure 2:
Overall Survival in All Patients with Rhabdomyosarcoma by Anaplasia Status
See this image and copyright information in PMC

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