Regional lymph node invasion in pediatric non-rhabdomyosarcoma soft tissue sarcoma: an international cohort study from the International Soft Tissue Sarcoma Consortium.

Background: In pediatric non-rhabdomyosarcoma soft tissue sarcoma (NRSTS), the frequency and prognostic impact of regional lymph node involvement (N1) are not clearly defined and may vary according to histological type. We therefore to analyze the rate of N1 at diagnosis, the pattern of nodal relapse, and the prognostic impact of N1 in pediatric patients with NRSTS.

Methods: Data were collected and analyzed through the International Soft Tissue SaRcoma ConsorTium (INSTRuCT). Patients aged 0-21 years with NRSTS prospectively enrolled in European and North American cooperative group trials from October 1, 1990 to October 1, 2018 were included. Descriptive statistics, logistic regressions, and Cox proportional hazards models were used to analyze the data and assess prognostic factors.

Findings: 1937 patients were eligible for inclusion. The main histotypes were synovial sarcoma (628 cases; 32%), undifferentiated/unclassified sarcoma (396 cases, 20%) and malignant peripheral nerve sheath tumor (275 cases, 14%). Distant metastases were present in 197 (10.2%) patients. N1 was present in 152 (7.8%) patients. With a median follow-up of 7.2 years (95% CI 7.0-7.4), 615 patients (31.7%) had local relapse or progression, 30 (1.5%) had nodal relapse (including four with initial N1), and 287 (14.8%) developed metastases. In multivariate analysis, node positive (N1) status was associated with high pathologic grade (p = 0.010) and distant metastasis (p < 0.0001), but not with tumor size, invasiveness, and histological subgroups (p = 0.36). For non-metastatic tumors (1740 cases), metastatic-free-survival differed between node negative N0 and N1 patients, but overall survival, event-free-survival and nodal relapse-free-interval did not.

Interpretation: N1 is rare in NRSTS during childhood (<8%) and mainly presents in a subset of histotypes. Regional nodal control at 5 years is adequate. However, N1 in NRSTS is a marker of aggressive disease.

Funding: Cancer Research Foundation, Children's Research Foundation, Comer Development Board, KickCancer, King Baudouin Foundation, Rally Foundation for Childhood Cancer Research, Seattle Children's Foundation from Kat's Crew Guild through the Scleroderma Research Foundation, St. Baldrick's Foundation, The Andrew McDonough B+ Foundation, Maddie's Promise, Summer's Way Foundation, Friends of T.J. Foundation, Sebastian Strong, Children's Oncology Group Foundation, and the Sarah Jane Adicoff Endowment for Research in Rhabdomyosarcoma through the Seattle Children's Foundation.