Practical guideline for rhabdomyosarcoma in children and adolescents

Rhabdomyosarcoma (RMS) is classified as a rare tumor1; however, it represents the most prevalent form of soft tissue sarcoma (STS) among children and adolescents, comprising approximately 50% of all STS cases diagnosed. RMS is a high-grade, malignant neoplasm that originates from mesenchymal cells and exhibits characteristics of muscle differentiation. The disease primarily manifests in four major subtypes: alveolar RMS and embryonal RMS (ERMS), spindle cell/sclerosing RMS, and pleomorphic RMS, which are distinguishable based on their histopathological characteristics. The prognosis for children with widely metastatic and recurrent RMS remains poor.2 Ongoing research into the mechanisms and pathophysiology of RMS continues to advance. These findings have led to the development of targeted and immune-based therapies, which are currently being investigated in clinical trials to improve outcomes for patients with RMS.2 Due to the rarity of such pediatric tumors, children with RMS often endure prolonged, intensive, and multifaceted therapeutic regimens that can result in life-threatening acute toxicities and, in some instances, lifelong adverse effects. This guideline aims to provide the latest mechanism research of RMS and provide the integrated solutions of several key clinical questions related to the diagnosis, staging, and treatment of RMS in children and adolescents, based on the latest evidence and recommendations from authoritative publications and expert consensus.

Methods

This guideline is developed based on the most recent published literature, encompassing clinical trials (both randomized controlled trials and single-arm clinical trials), observational studies, and expert consensus statements from authoritative organizations such as the American Intergroup RMS Study Group, the European Pediatric Soft Tissue Sarcomas Study Group, the Chinese Children Cancer Group, and other prominent pediatric cancer research and international pediatric oncology cooperative groups. This guideline was subsequently presented in a virtual meeting with all authors, where a final consensus was reached after multiple rounds of discussion. Recommendations were formulated based on the quality of evidence and the assessment of potential benefits versus harms. Levels of evidence and grades of recommendation were assigned according to the GRADE system.3 Statements without grading were considered justified standard clinical practice by the authors.

Clinical diagnosis and staging

RMS can occur in any part of the body, with the most common sites being the head and neck (40%), genitourinary tract (25%), and extremities (20%). Symptoms vary depending on the primary tumor site and may include swelling, pain, and dysfunction of the affected area (Figure 1). Biopsy is essential for definitive diagnosis and subclassification of RMS. Molecular detection for FOXO1 fusion gene further clarifies the classification and prognosis of rhabdomyosarcoma. Imaging studies such as computed tomography (CT), magnetic resonance imaging, and positron emission tomography-CT are used to determine the tumor’s size, location, and extent of invasion, as well as to assess for metastatic disease. The most metastatic site of RMS is lung, so chest imaging is necessary.