Experts Establish Radiation Treatment Guidelines for Pediatric Metastatic Rhabdomyosarcoma

An international consortium of pediatric oncology experts has published consensus guidelines on radiation treatment for children with metastatic rhabdomyosarcoma (RMS), offering site-specific recommendations for a disease that carries a 5-year overall survival rate of roughly 25% and has lacked standardized guidance.¹

The guidelines, developed by the International Soft Tissue Sarcoma Consortium (INSTRuCT) and published in Practical Radiation Oncology, cover various anatomic sites of metastasis and are graded by both strength of recommendation and quality of evidence.

A Closer Look at Rhabdomyosarcoma

RMS is the most common pediatric soft tissue sarcoma, and approximately 15% of patients present with metastatic disease at diagnosis. Outcomes are poor, and the 3-year event-free survival (EFS) rate sits between 27–35%. Management of the disease is complicated by the wide variation in where and how extensively the disease spreads.

INSTRuCT, a collaboration between the Children's Oncology Group, the European Paediatric Soft Tissue Sarcoma Study Group, and the Cooperative Weichteilsarkom Studiengruppe, convened its radiation oncology committee to develop these guidelines based on available evidence through July 2025. The process relied on multidisciplinary expert discussion rather than a formal Delphi process, which the authors acknowledged may limit methodological rigor.

Recommendations for Lung, Bone, Brain, Lymph Node, and Primary Tumor Radiation

The guidelines provide graded recommendations across the primary tumor site, regional and distant lymph nodes, lungs, bone, brain, liver/peritoneum, and soft tissue/skin. A central principle across all sites is that treating both the primary tumor and all initial sites of metastatic disease, when feasible, improves outcomes, supported by non-randomized multicenter data showing an overall survival benefit.

For the primary site, the panel gave a strong recommendation with high evidence for definitive local therapy, including radiation alone, surgery alone, or both, following neoadjuvant chemotherapy, at doses of 41.4 to 50.4 Gy in 23 to 28 fractions. Retrospective data from the European BERNIE study showed that patients who received combined radiation and surgery had markedly better 3-year overall survival (OS; 84%) than those who received either the modality alone or no local treatment at all.²

Lymph node involvement was also given a strong recommendation for radiation to the involved nodes and the nodal basin at the same dose range.¹ Sentinel lymph node assessment was specifically recommended for extremity and paratesticular primaries.

For lung metastases, which is the most common site of spread, the panel gave a conditional recommendation for whole lung irradiation (WLI) at 15 Gy in 10 fractions, noting that while WLI improves EFS in multiple studies, no OS benefit has been consistently demonstrated. Stereotactic ablative radiotherapy (SABR) at 30 to 60 Gy over 3 to 5 fractions is recommended for limited lesions, with fractionated rather than single-fraction regimens preferred. Notably, the authors cautioned against combining WLI with focal SABR.

For bone metastases, SABR at 24 Gy in 3 fractions or 30 to 35 Gy in 5 fractions is encouraged for limited disease. Palliative single-fraction dosing (8 Gy) is recommended for pain relief. Brain and abdominal metastases carry conditional recommendations based on lower-quality evidence, with stereotactic radiosurgery preferred for small-volume brain disease and whole abdominopelvic radiation considered for peritoneal involvement after surgical debulking.

Why Standardized Radiation Guidance Is Overdue

Prognostic stratification using the Oberlin score, which weighs adverse factors including age, number of metastatic sites, and bone or bone marrow involvement, remains central to guiding treatment intensity. Patients with 0 or 1 Oberlin risk factors have a 3-year EFS of 44%, while those with 2 to 4 risk factors face only 14%. These guidelines help align radiation decisions with prognosis across a heterogeneous patient population that spans multiple cooperative groups with historically different protocols.

The authors underscored that high-level prospective evidence remains scarce and that much of what guides these recommendations comes from retrospective cohorts and non-randomized comparisons. A key randomized arm within the FaR-RMS trial, which compared radiation to all metastatic sites to the primary site and regional nodes only, closed early due to insufficient accrual, highlighting how difficult it remains to conduct rigorous trials in this population.

Guidelines Offer a Practical Framework, but Prospective Evidence, Trial Enrollment Remain Critical

For a disease defined by limited survival and clinical complexity, these INSTRuCT guidelines fill an important void. They offer a practical, evidence-anchored framework that can be applied across institutions and countries while also acknowledging the gaps that remain. Multidisciplinary collaboration and continued clinical trial enrollment are essential to moving the field forward.

“While the evidence is limited, these consensus guidelines highlight consensus positions regarding best practice treatment to give assistance to providers as they navigate treatment decisions for their pediatric patients with metastatic RMS,” the authors wrote.

References

1. Chang L, Cameron A, Murphy BM, et al. Recommendations for radiation treatment in pediatric patients with metastatic rhabdomyosarcoma: Expert consensus from the International Soft Tissue SaRcoma ConsorTium (INSTRuCT). Pract Radiat Oncol. Published online May 6, 2026. doi:10.1016/j.prro.2026.04.016
2. Cameron AL, Elze MC, Casanova M, et al. The impact of radiation therapy in children and adolescents with metastatic rhabdomyosarcoma. Int J Radiat Oncol Biol Phys. 2021;111(4):968-978. doi:10.1016/j.ijrobp.2021.06.031