2375 - Leptomeningeal Failure in Pediatric Parameningeal Rhabdomyosarcoma: Predictive Factors and Opportunities for Prevention
Presenter(s)
N. Shah1, M. Rupji2, C. Stokes3, T. Cash3, S. Mitchell3, K. S. Sutton3, N. Esiashvili4, and B. R. Eaton4; 1AU/UGA Medical Partnership, Athens, GA, 2Department of Biostatistics & Bioinformatics, Rollins School of Public Health, and Winship Cancer Institute at Emory University, Atlanta, GA, 3Aflac Cancer and Blood Disorders Center, Children’s Healthcare of Atlanta, and Emory University School of Medicine, Atlanta, GA, 4Department of Radiation Oncology, Winship Cancer Institute of Emory University, Atlanta, GA
Purpose/Objective(s): Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children. Parameningeal (PM) RMS, a high-risk head-and-neck subtype, has poor outcomes due to limited surgical options, frequent intracranial extension (ICE) and increased risk of leptomeningeal dissemination (LMD). This study investigates the incidence, risk factors, and outcomes associated with LMD in pediatric PM RMS.
Materials/Methods: Children with PM RMS treated from 2000-2025 were reviewed. Data included baseline tumor features, treatment details, and recurrence patterns. Statistical analyses included Kaplan-Meier survival estimates and Cox regression analysis for relapse-free survival (RFS)/overall survival (OS) and competing risk framework for LMD analysis. In the multivariable analysis, a backward selection approach was used to retain only variables that were statistically significant with survival outcome.
Results: Among the 48 patients (48% female), median age was 7 years (range 1-19), 18 (38%) had alveolar histology, thirty-nine (81%) were stage 2/3, 31 (67%) had tumors =5cm, and 35 (73%) presented with radiographically apparent ICE. Chemotherapy included high dose (HD)-(vincristine [V], actinomycin [A], and cyclophosphamide [C; 2200 mg/m2]) (n=25), V, doxorubicin (D), C/ifosfamide (I), etoposide (E) (n=14), or lower cumulative cyclophosphamide dose regimens (n=9). Radiation treatment included proton (n=22) or photon therapy (n=26) to a median dose of 50.4 Gy (RBE) (range 30.6-59.4 Gy). Median follow-up time was 9.02 years [95% CI (4.88-13.08)]. )]. RFS and OS rates were 53.1% and 61.6% at 5 years and 53.1% and 55.1% at 10 years, respectively. On multivariable analysis, lower disease stage (Stage 2/3 vs 4) was the only variable significantly associated with longer RFS (HR: 0.10, 95% CI 0.04-0.30, p<0.001) and OS (HR: 0.25, 95% CI 0.08-0.81, p=0.002). Eighteen (38%) patients progressed with LMD (n=10), local failure (n=6), or distant systemic failure alone (n=2). The cumulative incidence of LMD at one year was 19.8% (95% CI 10.4%, 37.6%) among all patients. LMD occurred in 10/35 (29%) patients with ICE at presentation. On multivariable analysis, presence of ICE (p=0.001) and higher RT dose (HR 1.16, 95% CI 1.02-1.32, p=0.026) were significantly associated with greater cumulative incidence of LMD, and lower stage (HR 0.19, 95% CI 0.06-0.58, p=0.004) was significantly associated with a lower risk of LMD failure. In an exploratory analysis among patients with ICE, LMD failure occurred in 2/11 (18%) patients treated with VDC/IE vs. 7/18 (38%) HD-VAC or 1/5 (20%) lower dose chemotherapy; 4/19 (21%) patients starting RT at = week 4 vs. 6/16 (37%) starting RT later, and 3/18 (17%) receiving photon therapy vs. 7/10 (41%) receiving proton therapy.
Conclusion: LMD is the most common pattern of failure among patients with PM RMS with ICE. Novel treatment strategies for this patient population are needed to reduce the risk of LMD failure and improve clinical outcomes.