Welcome to the Science Spotlight, where we highlight the scientific advancements made possible by our consortia and data commons.
The International Soft Tissue Sarcoma Consortium (INSTRuCT), working in collaboration with Data for the Common Good (D4CG) through the Pediatric Cancer Data Commons (PCDC), has recently reached a major milestone: the publication of their first data-driven research papers.
After years of harmonizing clinical trial data from major cooperative groups across North America and Europe and producing numerous consensus papers, the consortium is now using the PCDC to access and analyze standardized data from thousands of soft-tissue sarcoma patients treated over decades. In these publications, INSTRuCT researchers demonstrate the value of the PCDC with new findings that will inform clinical decision-making and treatment strategies for pediatric soft tissue sarcomas.
New insights into lymph node involvement
Regional lymph node invasion in pediatric non-rhabdomyosarcoma soft tissue sarcoma: an international cohort study from the International Soft Tissue Sarcoma Consortium, published in eClinicalMedicine, examined lymph node involvement in non-rhabdomyosarcoma soft tissue sarcomas by analyzing data from 1,937 patients treated between 1990 and 2018. While regional lymph node metastasis is rare overall, affecting fewer than 8 percent of patients, the research revealed that it occurs much more frequently in specific tumor types, with angiosarcoma, clear cell sarcoma, epithelioid sarcoma, undifferentiated pleomorphic and undifferentiated/unclassified sarcomas all showing lymph node involvement rates above 10 percent. For these high-risk histologies, the findings support comprehensive imaging of regional lymph nodes and pathological sampling when abnormalities are detected. This research offers clinicians evidence-based guidance for determining when comprehensive lymph node imaging is essential.
The study also found that lymph node involvement correlates most strongly with high pathologic grade and distant metastases, positioning it as a marker of aggressive disease biology rather than an independent driver of poor outcomes. Importantly, the research also confirmed that current treatment approaches for regional nodal control are adequate, with 5-year control rates above 95 percent.
Prognosis differences in metastatic rhabdomyosarcoma
Single site metastatic rhabdomyosarcoma: An INternational Soft Tissue saRcoma ConsorTium (INSTRuCT) pooled analysis, published in the European Journal of Cancer, analyzed 497 patients with single-site metastatic rhabdomyosarcoma, revealing that the location of metastasis as well as molecular markers significantly impact prognosis and should inform treatment decisions.
Patients with disease confined to the lungs, distant lymph nodes, or certain other sites demonstrated 5-year survival rates approaching or exceeding 50 percent, substantially better than those with bone metastases or bone marrow involvement. These differences likely reflect both disease biology and the feasibility of delivering effective local therapy to accessible sites.
The study also highlighted the predictive power of molecular markers. Among patients with available fusion gene data, fusion-negative status was associated with dramatically better outcomes across multiple metastatic sites. For example, in lung-only metastases, fusion-negative patients showed nearly 50 percent five-year event-free survival compared to just 10 percent for fusion-positive cases. These findings suggest that future clinical trials should stratify patients by both anatomic site and molecular characteristics, potentially allowing more tailored treatment approaches.
The foundation: years of data harmonization
These research milestones would not have been possible without INSTRuCT’s collaborative model and extensive work with D4CG to collect and harmonize data. The International Soft Tissue Sarcoma Consortium: The baseline analysis of rhabdomyosarcoma data, published in Cancer, details how the consortium harmonized data from 6,972 rhabdomyosarcoma patients across 16 clinical trials conducted between 1990 and 2016, representing the collaborative work of the Children’s Oncology Group, European Paediatric Soft Tissue Sarcoma Study Group, Cooperative Weichteilsarkom Studiengruppe, and earlier international efforts.
Creating this resource has required standardized definitions, resolution of diagnostic criteria that evolved over decades, and the technical infrastructure to ensure diverse data could be analyzed together while protecting patient privacy. D4CG’s stewardship of this complex process through the PCDC has helped to transform separate institutional datasets into a robust resource now driving actionable scientific discovery. As INSTRuCT continues their work, families facing pediatric soft tissue sarcoma diagnoses and the clinicians who treat them will increasingly benefit from the evidence-based insights that only large-scale international collaboration can provide.
