Prognostic factors in patients with localized and metastatic alveolar rhabdomyosarcoma. A report from two studies and two registries of the Cooperative Weichteilsarkom Studiengruppe CWS

IF 2.9 2区医学 Q2 ONCOLOGY

Cancer Medicine Pub Date : 2025-01-09 DOI:10.1002/cam4.70215

Ewa Koscielniak, Sabine Stegmaier, Gustaf Ljungman, Bernarda Kazanowska, Felix Niggli, Ruth Ladenstein, Bernd Blank, Erika Hallmen, Christian Vokuhl, Claudia Blattmann, Monika Sparber-Sauer, Thomas Klingebiel

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引用次数: 0

Abstract

Background

The histologic classification of rhabdomyosarcoma (RMS) as alveolar (aRMS) or embryonal (eRMS) is of prognostic importance, with the aRMS being associated with a worse outcome. Specific gene fusions (PAX3/7::FOXO1) found in the majority of aRMS have been recognized as markers associated with poor prognosis and are included in current risk stratification instead of histologic subtypes in localized disease. In metastatic disease, the independent prognostic significance of fusion status has not been definitively established. The objective of this analysis was to evaluate survival outcomes of patients with localized and metastatic aRMS and its association with fusion status and subtype (PAX3/7::FOXO1, FOXO1 break), and clinical prognostic factors.

Methods

A total of 470 patients with aRMS ≤21 years of age enrolled in two CWS-trials and two registries was eligible for the analysis.

Results

The 5-year event-free survival (EFS) and overall survival (OS) rates for all patients with localized vs. metastatic tumors were: 56% and 65% vs. 18% and 22%, respectively. Of the 368 (78%) tumors tested, specific fusion was found in 330 (90%), considered “fusion positive” FP (PAX3::FOXO1 in 280, PAX7::FOXO1 in 49, FOXO1 break in 59 tumors). In patients with localized tumors, univariate analysis revealed that clinical group, tumor invasiveness (T1 vs.T2), regional lymph node involvement (N0 vs. N1) and FOXO1 fusion were significantly associated with EFS and OS, tumor size and PAX variant with OS only. In patients with metastatic aRMS, age, bone/marrow (B/BM) metastases, FOXO1 fusion and PAX variant were associated with EFS and OS, T status with OS only. Multivariate analysis identified PAX3::FOXO1 fusion as an independent adverse prognostic factor for EFS in patients with localized disease and for EFS and OS in patients with metastatic disease, B/BM metastases for EFS.

Conclusion

PAX3::FOXO1 fusion should replace FOXO1 fusion as an adverse prognostic factor in risk stratification. The prognostic relevance of PAX7::FOXO1-positive and FOXO1 fusion negative aRMS, along with the clinical factors described in this report, allows further refinement of risk assessment of patients with localized and metastatic aRMS.

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局部和转移性肺泡横纹肌肉瘤患者的预后因素。来自两项研究和CWS合作研究小组的两份登记的报告。

背景：横纹肌肉瘤（RMS）的组织学分类为肺泡型（aRMS）或胚胎型（eRMS）对预后具有重要意义，而胚胎型与较差的预后相关。在大多数aRMS中发现的特异性基因融合（PAX3/7::FOXO1）已被认为是与预后不良相关的标志物，并被纳入当前的风险分层，而不是局部疾病的组织学亚型。在转移性疾病中，融合状态的独立预后意义尚未明确确立。本分析的目的是评估局部和转移性aRMS患者的生存结果及其与融合状态和亚型（PAX3/7::FOXO1, FOXO1 break）以及临床预后因素的关系。方法：共有470例aRMS≤21岁的患者参加了两项cws试验和两个注册中心，符合分析条件。结果：所有局部和转移性肿瘤患者的5年无事件生存率（EFS）和总生存率（OS）分别为56%和65%，18%和22%。在368例（78%）肿瘤中，有330例（90%）发现特异性融合，被认为是“融合阳性”FP（280例PAX3::FOXO1, 49例PAX7::FOXO1, 59例FOXO1断裂）。在局限性肿瘤患者中，单因素分析显示，临床分组、肿瘤侵袭性（T1 vs. t2）、局部淋巴结累及（N0 vs. N1）和FOXO1融合与EFS和OS、肿瘤大小和PAX变异（仅OS）显著相关。在转移性aRMS患者中，年龄、骨/骨髓（B/BM）转移、FOXO1融合和PAX变异与EFS和OS相关，T状态仅与OS相关。多因素分析发现PAX3::FOXO1融合是局限性疾病患者EFS和转移性疾病患者EFS和OS的独立不良预后因素，B/BM转移为EFS。结论：PAX3: FOXO1融合应取代FOXO1融合作为危险分层的不良预后因素。PAX7:: fox01阳性和fox01融合阴性aRMS与预后的相关性，以及本报告中描述的临床因素，可以进一步完善局限性和转移性aRMS患者的风险评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cancer Medicine ONCOLOGY-

CiteScore

5.50

自引率

2.50%

发文量

907

审稿时长

19 weeks

期刊介绍： Cancer Medicine is a peer-reviewed, open access, interdisciplinary journal providing rapid publication of research from global biomedical researchers across the cancer sciences. The journal will consider submissions from all oncologic specialties, including, but not limited to, the following areas: Clinical Cancer Research Translational research ∙ clinical trials ∙ chemotherapy ∙ radiation therapy ∙ surgical therapy ∙ clinical observations ∙ clinical guidelines ∙ genetic consultation ∙ ethical considerations Cancer Biology: Molecular biology ∙ cellular biology ∙ molecular genetics ∙ genomics ∙ immunology ∙ epigenetics ∙ metabolic studies ∙ proteomics ∙ cytopathology ∙ carcinogenesis ∙ drug discovery and delivery. Cancer Prevention: Behavioral science ∙ psychosocial studies ∙ screening ∙ nutrition ∙ epidemiology and prevention ∙ community outreach. Bioinformatics: Gene expressions profiles ∙ gene regulation networks ∙ genome bioinformatics ∙ pathwayanalysis ∙ prognostic biomarkers. Cancer Medicine publishes original research articles, systematic reviews, meta-analyses, and research methods papers, along with invited editorials and commentaries. Original research papers must report well-conducted research with conclusions supported by the data presented in the paper.