title: Definitive intensity modulated radiotherapy in locally advanced hypopharygeal and laryngeal squamous cell carcinoma: mature treatment results and patterns of locoregional failure.
abstract: OBJECTIVE
  To 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.
  
  
  METHODS
  Data 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).
  
  
  RESULTS
  Fifty 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.
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, Freiburgstrasse, 3010, Bern, Switzerland. Andreas.Geretschlaeger@claraspital.ch.
authors.forename: Andreas
authors.initials: A
authors.lastname: Geretschläger
authors.affiliation: Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, Freiburgstrasse, 3010, Bern, Switzerland. beat.bojaxhiu@insel.ch.
authors.forename: Beat
authors.initials: B
authors.lastname: Bojaxhiu
authors.affiliation: Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, Freiburgstrasse, 3010, Bern, Switzerland. alan.dalpra@insel.ch.
authors.forename: Alan
authors.initials: A
authors.lastname: Dal Pra
authors.affiliation: Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, Freiburgstrasse, 3010, Bern, Switzerland. Dominic.Leiser@insel.ch.
authors.forename: Dominic
authors.initials: D
authors.lastname: Leiser
authors.affiliation: Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, Freiburgstrasse, 3010, Bern, Switzerland. Michael.Schmuecking@insel.ch.
authors.forename: Michael
authors.initials: M
authors.lastname: Schmücking
authors.affiliation: Department of Otorhinolaryngology, Bern University Hospital, Freiburgstrasse, 3010, Bern, Switzerland. Andreas.Arnold@insel.ch.
authors.forename: Andreas
authors.initials: A
authors.lastname: Arnold
authors.affiliation: Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, Freiburgstrasse, 3010, Bern, Switzerland. pirus.ghadjar@charite.de.
authors.forename: Pirus
authors.initials: P
authors.lastname: Ghadjar
authors.affiliation: Department of Radiation Oncology, Inselspital, Bern University Hospital and University of Bern, Freiburgstrasse, 3010, Bern, Switzerland. Daniel.Aebersold@insel.ch.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Aebersold
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D007822:Laryngeal Neoplasms / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D008175:Lung Neoplasms / Q000401:mortality / Q000532:radiotherapy* / Q000556:secondary; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D009367:Neoplasm Staging; D011379:Prognosis; D011879:Radiotherapy Dosage; D050397:Radiotherapy, Intensity-Modulated / Q000379:methods*; D012189:Retrospective Studies; D015996:Survival Rate