title: Final long-term results of a phase I/II study of dose-escalated intensity-modulated radiotherapy for locally advanced laryngo-hypopharyngeal cancers.
abstract: OBJECTIVE
  We previously described dose-escalated intensity-modulated radiotherapy (IMRT) in squamous cell cancer of the larynx/hypopharynx (SCCL/H) to offer improved locoregional control with a low incidence of toxicity at 2 years. We now present outcome and safety data at 5 years.
  
  
  METHODS
  A sequential cohort Phase I/II trial design was used. Patients with SCCL/H received IMRT at two dose levels (DL): DL1, 63 Gy/28 fractions to planning target volume 1 (PTV1) and 51.8 Gy/28 Fx to PTV2; DL2, 67.2 Gy/28 Fx and 56 Gy/28 Fx to PTV1 and PTV2, respectively. Patients received induction cisplatin/5-fluorouracil and concomitant cisplatin.
  
  
  RESULTS
  Between 09/2002 and 01/2008, 60 patients (29 DL1, 31 DL2) with stage III (41% DL1, 52% DL2) and stage IV (52% DL1, 48% DL2) disease were recruited. Median (range) follow-up for DL1 was 5.7 (1.0-10.2) years and for DL2 was 6.0 (0.3-8.4) years. Five-year local control rates (95% confidence interval) for DL1 and DL2, respectively, were 68% (50.6-85.4%) and 75% (58.9-91.1%), locoregional progression-free survival rates were 54% (35.6-72.4%) and 62.6% (44.8-80.4%), and overall survival was 61.9% (44.1-79.7) and 67.6 (51.1-84.1%). Five-year laryngeal preservation rates were 66.7% (37.4-87.9%) and 71.4% (44.4-85.8%), respectively. Cumulative toxicities reported were: one patient in DL1 and 2 in DL2 developed benign pharyngeal strictures. No other G3/4 toxicities were reported.
  
  
  CONCLUSIONS
  Dose-escalated IMRT at DL2 achieves higher 5-year local control, larynx preservation and survival rates with acceptable late toxicity. Recruitment into a Cancer Research UK Phase III study (ART-DECO), with DL2 as the experimental arm, is ongoing.
authors.affiliation: Head and Neck Unit, Royal Marsden Hospital, London, UK; The Institute of Cancer Research, London, UK.
authors.forename: Dorothy M
authors.initials: DM
authors.lastname: Gujral
authors.affiliation: Head and Neck Unit, Royal Marsden Hospital, London, UK.
authors.forename: Aisha B
authors.initials: AB
authors.lastname: Miah
authors.affiliation: Department of Statistics, Royal Marsden Hospital, London, UK.
authors.forename: Shankar
authors.initials: S
authors.lastname: Bodla
authors.affiliation: Head and Neck Unit, Royal Marsden Hospital, London, UK; The Institute of Cancer Research, London, UK.
authors.forename: Thomas M
authors.initials: TM
authors.lastname: Richards
authors.affiliation: Head and Neck Unit, Royal Marsden Hospital, London, UK; The Institute of Cancer Research, London, UK.
authors.forename: Liam
authors.initials: L
authors.lastname: Welsh
authors.affiliation: Head and Neck Unit, Royal Marsden Hospital, London, UK; The Institute of Cancer Research, London, UK.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Schick
authors.affiliation: Head and Neck Unit, Royal Marsden Hospital, London, UK; The Institute of Cancer Research, London, UK.
authors.forename: Ceri J
authors.initials: CJ
authors.lastname: Powell
authors.affiliation: Department of Physics, Royal Marsden Hospital, London, UK.
authors.forename: Catharine H
authors.initials: CH
authors.lastname: Clark
authors.affiliation: The Institute of Cancer Research, London, UK; Department of Physics, Royal Marsden Hospital, London, UK.
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Bidmead
authors.affiliation: Head and Neck Unit, Royal Marsden Hospital, London, UK.
authors.forename: Lorna
authors.initials: L
authors.lastname: Grove
authors.affiliation: Head and Neck Unit, Royal Marsden Hospital, London, UK; The Institute of Cancer Research, London, UK.
authors.forename: Teresa
authors.initials: T
authors.lastname: Guerrero-Urbano
authors.affiliation: Head and Neck Unit, Royal Marsden Hospital, London, UK; The Institute of Cancer Research, London, UK.
authors.forename: Shreerang A
authors.initials: SA
authors.lastname: Bhide
authors.affiliation: Head and Neck Unit, Royal Marsden Hospital, London, UK.
authors.forename: Kate L
authors.initials: KL
authors.lastname: Newbold
authors.affiliation: Head and Neck Unit, Royal Marsden Hospital, London, UK; The Institute of Cancer Research, London, UK.
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Harrington
authors.affiliation: Head and Neck Unit, Royal Marsden Hospital, London, UK; The Institute of Cancer Research, London, UK. Electronic address: Christopher.Nutting@rmh.nhs.uk.
authors.forename: Christopher M
authors.initials: CM
authors.lastname: Nutting
mesh_terms: D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000532:radiotherapy*; D007822:Laryngeal Neoplasms / Q000532:radiotherapy*; D050397:Radiotherapy, Intensity-Modulated
keywords: Dose-escalation; Hypopharynx; IMRT; Larynx