Intensity Modulated Radiotherapy for Squamous Cell Carcinoma of the Hypopharynx and Larynx: Clinical Outcomes and Patterns of Failure

Abstract

Limited clinical data exists in the use of intensity-modulated radiotherapy (IMRT) for cancers of the hypopharynx (HP) and larynx (LX). This study reports the clinical outcomes and patterns of failure in patients treated with IMRT for squamous cell cancers (SCC) of these sites. Between 9/2001 and 12/2007, 42 patients with newly diagnosed SCC of the HP (23) and LX (19) were treated with IMRT with curative intent at Stanford University Medical Center. Six patients were treated in the postoperative setting with uninvolved surgical margins, 5 received post-operative radiotherapy with involved margins or gross residual disease, and 31 underwent definitive radiotherapy. Seventeen patients received concurrent cisplatin-based chemotherapy, 13 received non-cisplatin based regimens with or without Cetuximab, 6 received Cetuximab monotherapy and 6 received no systemic therapy. Treatment plans were designed to provide a median dose of ≥66 Gy at 2.2 Gy/fraction to >95% of the gross tumor volume (GTV) in the definitive setting and to post-operative cases with positive margins, and a median dose of 60 Gy at 2 Gy/fraction in the post-operative setting with clear margins. Median follow-up was 14 months among surviving patients (range, 5-64 months). In patients with local or regional failure, imaging studies delineating the site of failure were co-registered to the treatment planning CT when available to aid in determining site of failure in relation to the treatment plan. Five patients developed a locoregional failure or had persistent disease, with a median time to failure of 12.1 months. Three local failures occurred entirely within the high-dose region, 1 of whom had synchronous bony metastatic disease, and 2 occurred in irradiated regional nodes, 1 of whom had synchronous distant metastasis. No marginal misses were observed. Seven patients developed distant metastasis as the initial site of failure. The 2-year Kaplan-Meier estimates of locoregional control, freedom from distant metastasis, overall survival, and disease-free survival (DFS) were 82%, 79%, 62%, and 57%, respectively. On univariate analysis, HP primaries had a statistically significant lower DFS than LX primaries. T-classification, overall stage, histologic grade, and age did not predict for DFS. IMRT provided excellent LRC for patients with SCC of the HP and LX. Pattern of failure analysis showed that locoregional relapses occurred in the high-dose volumes, suggesting that target volume delineation was adequate but further dose-escalation may be needed. HP tumors faired worse than LX tumors, suggesting that these patients may warrant more aggressive treatment.