New Pediatric Soft Tissue Sarcoma Guidelines Emphasize Risk Stratification, Clinical Trials

The National Comprehensive Cancer Network (NCCN) published new guidelines for pediatric soft tissue sarcoma (STS), growing the NCCN’s library of guidelines to now cover 91 topics in cancer care.¹

Pediatric STS makes up nearly 7% of all childhood cancers and is categorized into two subtypes: rhabdomyosarcoma (RMS) and nonrhabdomyosarcoma STS.²

The new NCCN guidelines emphasize risk stratification, diagnosis, patient monitoring, and the value of various screening tools to assess RMS. RMS is the more common variant of the cancer in children and people under the age of 20, as it accounts for nearly 5% of childhood cancers.¹ The guidelines provide extensive references to screening for target diagnostic difficulties associated with RMS, as it can appear anywhere on the body. It can present on the head, neck, or limbs, or as a bump with or without pain. It can also occur on internal organs, making breathing or urination difficult. These guidelines aim to find a balance between the goal of a cure and minimizing adverse events to optimize patient outcomes.¹

“RMS can be divided into specific subtypes that are driven by different genetic changes that can influence outcomes. Those changes and other clinical and pathology features are all incorporated into the multifaceted treatments,” Stephen Skapek, MD, chair of the NCCN Guidelines Panel for Pediatric Soft Tissue Sarcoma, said in a press release. “That’s why it was essential to form a group of leading, multidisciplinary experts from across the country to put together a roadmap for diagnosing, risk-stratifying, and treating these patients.”

Key treatment options for patients outlined in the guideline include surgery, systemic therapy, and radiation therapy. Surgery was listed as the primary approach with the goal of complete tumor resection with clear margins. However, site-specific surgical principles are emphasized to preserve function, but upfront resection isn’t amenable. These sites can include orbital, parameningeal, or vulvar, and in these instances, a biopsy followed by systemic therapy is recommended.³

Radiation therapy was recommended to be used as an adjunct to surgery, especially when margin-negative resection was not achieved or for local control in high-risk tumors.

Systemic therapy, which includes chemotherapy and targeted therapies, was another key treatment option. For patients with a low, very low, or intermediate risk of RMS, vincristine/dactinomycin/cyclophosphamide therapy was recommended either concurrently with other therapies or integrated within a clinical trial.

The guidelines emphasized the importance of clinical trials as a preferred component of patient care, specifically encouraging them whenever applicable and feasible. The strong preference for clinical trial participation aims to optimize treatment options, contribute to evidence generation, and improve patient outcomes.

The key screening options outlined in the guidelines underscore the importance of monitoring treatment responses using various image modalities. These included chest X-rays, computed tomography, magnetic resonance imaging, whole-body scans, and lymphoscintigraphy. Monitoring strategies were tailored to individual risk, tumor site, and response.

The updated guidelines also provide detailed recommendations for workup and long-term surveillance, including biopsy-based diagnosis, radiographic staging, and molecular profiling such as FOXO1 fusion testing. Imaging strategies are tailored by tumor site and risk group, with MRI, chest CT, and FDG-PET playing key roles in staging and monitoring response. Survivorship planning is emphasized as cure rates rise, addressing late effects of chemotherapy, radiation, surgery, and genetic predisposition syndromes.

Both key therapy and screening options recommended a multidisciplinary approach to detecting recurrences and maintaining positive responses to treatments.

“When treating someone so young, you are not looking to just prolong survival; the goal is a full cure with minimal side effects and zero recurrence,” Douglas Hawkins, MD, NCCN panel vice-chair, said in the press release.



References:
1. New guidelines from NCCN detail fundamental differences in cancer in children compared to adults. NCCN. February 17, 2026. Accessed February 17, 2026. https://www.nccn.org/home/news/newsdetails?NewsId=5421
2. McCrear S. Poland launches nationwide liquid biopsy program for pediatric STS care. AJMC^®. January 15, 2026. Accessed February 17, 2026. https://www.ajmc.com/view/poland-launches-nationwide-liquid-biopsy-program-for-pediatric-sts-care
3. NCCN. Clinical Practice Guidelines in Oncology. Pediatric soft tissue sarcoma, version 1.2026. Accessed February 17, 2026. https://www.nccn.org/professionals/physician_gls/pdf/ped_sts.pdf