Abstract
PurposeTo assess clinical outcomes and patterns of loco-regional failure (LRF) in relation to clinical target volumes (CTV) in patients with locally advanced hypopharyngeal and laryngeal squamous cell carcinoma (HL-SCC) treated with definitive intensity modulated radiotherapy (IMRT) and concurrent systemic therapy.MethodsData from HL-SCC patients treated from 2007 to 2010 were retrospectively evaluated. Primary endpoint was loco-regional control (LRC). Secondary endpoints included local (LC) and regional (RC) controls, distant metastasis free survival (DMFS), laryngectomy free survival (LFS), overall survival (OS), and acute and late toxicities. Time-to-event endpoints were estimated using Kaplan-Meier method, and univariate and multivariate analyses were performed using Cox proportional hazards models. Recurrent gross tumor volume (RTV) on post-treatment diagnostic imaging was analyzed in relation to corresponding CTV (in-volume, > 95% of RTV inside CTV; marginal, 20–95% inside CTV; out-volume, < 20% inside CTV).ResultsFifty patients (stage III: 14, IVa: 33, IVb: 3) completed treatment and were included in the analysis (median follow-up of 4.2 years). Three-year LRC, DMFS and overall survival (OS) were 77%, 96% and 63%, respectively. Grade 2 and 3 acute toxicity were 38% and 62%, respectively; grade 2 and 3 late toxicity were 23% and 15%, respectively. We identified 10 patients with LRF (8 local, 1 regional, 1 local + regional). Six out of 10 RTVs were fully included in both elective and high-dose CTVs, and 4 RTVs were marginal to the high-dose CTVs.ConclusionThe treatment of locally advanced HL-SCC with definitive IMRT and concurrent systemic therapy provides good LRC rates with acceptable toxicity profile. Nevertheless, the analysis of LRFs in relation to CTVs showed in-volume relapses to be the major mode of recurrence indicating that novel strategies to overcome radioresistance are required.
Highlights
Radical surgical treatment of locally advanced squamous cell carcinoma of the hypopharynx or larynx (HL-SCC) often requires total laryngectomy (TL)
Landmark clinical trials for laryngeal [1] and hypopharyngeal cancers [2] have shown that organ preserving treatments such as induction chemotherapy followed by radiotherapy (RT)
In a prospective randomized trial, parotid-sparing intensity-modulated radiotherapy (IMRT) significantly reduced xerostomia compared to 3D conformal RT [7]
Summary
Radical surgical treatment of locally advanced squamous cell carcinoma of the hypopharynx or larynx (HL-SCC) often requires total laryngectomy (TL). Landmark clinical trials for laryngeal [1] and hypopharyngeal cancers [2] have shown that organ preserving treatments such as induction chemotherapy followed by radiotherapy (RT). In the last decade intensity-modulated radiotherapy (IMRT) has replaced 3D conformal RT for definitive treatment of locally advanced head-and-neck cancers due to the highly conformal dose distribution with steep gradients towards the surrounding healthy tissues thereby. A tight conformal dose distribution might instead increase the likelihood of geographical miss and locoregional failure (LRF) [8]. Having introduced IMRT in our institutional clinical practice in 2002, we reevaluated and adapted our guidelines for target volume definition for HL-SCC in 2007 drawing upon our own experience as well as early publications on IMRT in head-and-neck cancers [9,10,11]. With the aim of further improving treatment results through continuous analysis of our LRF patterns we have retrospectively analyzed mature clinical outcomes and toxicity patterns of a cohort of patients treated from 2007 onwards according to these standards
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