High Incidence of Local and Regional Failure in Pediatric Rhabdomyosarcoma of the Nasal ALA

Abstract

Primary site impacts treatment and outcome in pediatric rhabdomyosarcoma (RMS). It has been our observation that children with nasal ala RMS have more frequent local recurrences and regional nodal failures compared to other favorable head and neck sites. The purpose of this study was to evaluate clinical outcomes as well as factors that affect local control and survival in these patients with the goal of identifying strategies for improving disease control. We retrospectively identified 34 pediatric patients with RMS of the nasal ala and nasal/buccal region (nasal cavity primaries were excluded) diagnosed between September 1997 and September 2017 at 10 different pediatric cancer centers in the United States. Primary endpoints were local control (LC), failure-free survival (FFS), and overall survival (OS). Survival analysis was used to generate survival curves for each outcome. Cox regression was applied to model the hazard of event occurrence with bootstrap methods. Median age at diagnosis was 1.3 years (range 0.1 to 14 years). The majority were alveolar histology (n= 31). At diagnosis, 11 patients had regional nodal disease and no patients had metastasis. Primary tumor size was less than 5 cm in all cases. Clinical grouping was group I in one patient, group II in 13 patients, group III in 20 patients, and 7 patients underwent delayed primary excision (DPE). All patients received intermediate risk VAC-based chemotherapy except one patient with embryonal histology who received VA only. All patients received radiation therapy (RT) (range 30 to 50.4 Gy) to the primary disease site and any involved nodes if present. Median follow-up was 32 months (range 0.7 to 237 months). Twenty patients (59%) experienced at least one recurrence with a high frequency of local and regional nodal failures (5 local, 4 regional nodal, 5 local/regional nodal, 1 local/distant, 1 regional nodal/distant, 2 regional non-nodal, and 2 distant only). Median time to recurrence was 12.6 months (range 0.6 to 35.9 months). Three-year LC rate was 68%, FFS was 38% and OS was 68%. Seven patients (21%) are currently alive with disease due to ongoing salvage regimens. LC, FFS, and OS were not associated with cumulative cyclophosphamide dose or radiation dose. FFS and OS of pediatric RMS of the nasal ala and nasal/buccal region were notably below historical controls for non-orbital head and neck RMS. This may be related to the high frequency of young age and alveolar histology in this subsite. The present findings suggest that despite being a favorable site, these patients fare poorly with prior and current treatment algorithms, and re-evaluation of treatment strategies for these patients should be considered.