Regional Nodal Failure in Head and Neck Alveolar Rhabdomyosarcoma

Abstract

To assess clinical outcomes and patterns of failure, particularly regional control, for pediatric patients treated with proton therapy for head and neck alveolar rhabdomyosarcoma (HN-ARMS). Between 2006 and 2015, 14 patients with HN-ARMS were enrolled on a prospective registry protocol and treated with proton therapy at a single institution. Eight patients (57%) presented with localized disease, and 6 (43%) presented with regional nodal metastases. One patient (7%) with regional disease also had distant metastases. Ten patients (71%) were assessed for FOX01 status, and all had PAX3-FOX01 fusion transcripts. Primary site was parameningeal for 8 patients (57%), orbital for 3 patients (21%), and other head and neck for 3 patients (21%). All patients were enrolled on either COG or EpSSG protocols and treated with chemotherapy per protocol. All patients were treated with proton therapy to the primary site and involved nodal disease to median dose of 50.4 Gy(RBE) (range 39.6 – 50.4 Gy[RBE]). Elective nodal irradiation (ENI) was not used for patients without evidence of nodal disease (clinically or radiographically) at time of diagnosis. Median follow-up for surviving patients was 4.3 years. Five-year overall survival for the cohort (n = 14) was 50.2%. One patient (7%) experienced local failure, while 8 patients (57%) had regional nodal failures. Of 8 patients with no nodal disease at presentation, 6 had regional nodal failures (75%). There were no local or distant failures among these 8 patients. All 6 of these nodal regional failures involved first-echelon draining lymph node stations from the primary tumor site. Of 6 patients with nodal disease at presentation, one experienced concurrent in-field local failure and out-of-field regional failure in a nodal level where only the gross disease was treated. Another patient with nodal disease at presentation developed regional marginal failure, in a nodal basin initially involved by disease without target volume coverage of the entire nodal station. Additionally, there was no effect of the timing of proton therapy initiation on treatment failure. Proton therapy provides excellent local control for HN-ARMS. However, regional nodal failures were common among patients who did not have nodal disease at presentation. These data suggest that HN-ARMS patients may benefit from ENI. For node-positive patients, we recommend coverage of the entire nodal level due to observed high risk of failure at these sites.