title: Re-irradiation of adenoid cystic carcinoma: analysis and evaluation of outcome in 52 consecutive patients treated with raster-scanned carbon ion therapy.
abstract: BACKGROUND
  Treatment of local relapse in adenoid cystic carcinoma (ACC) following prior radiation remains a challenge: without the possibility of surgical salvage patients face the choice between palliative chemotherapy and re-irradiation. Chemotherapy yields response rates around 30% and application of tumouricidal doses is difficult due to proximity of critical structures. Carbon ion therapy (C12) is a promising method to minimize side-effects and maximize re-treatment dose in this indication. We describe our initial results for re-irradiation in heavily pre-treated ACC patients.
  
  
  METHODS
  Patients treated with carbon ion therapy between 04/2010 and 05/2013 (N=52pts, median age: 54 a) were retrospectively evaluated regarding toxicity (NCI CTC v.4), tumour response (RECIST) and control rates. 48pts (92.3%) received carbon ions only, 4pts received IMRT plus C12.
  
  
  RESULTS
  4pts were treated following R1-resection, 43pts for inoperable local relapse. Most common tumour sites were paranasal sinus (36.5%), parotid (19.2%), and base of skull (17.3%). Pts received a median dose of 51GyE C12/63Gy BED and cumulative dose of 128Gy BED [67-182Gy] after a median RT-interval of 61months. Median target volume was 93ml [9-618ml]. No higher-grade (>°II) acute reactions were observed, 7pts showed blood-brain-barrier changes (°I/II: 8pts; °III: 2pts), 1 pt corneal ulceration, xerophthalmia 7pts, °IV bleeding 1 pt, tissue necrosis 2pts, otherwise no significant late reactions. Objective response rate (CR/PR) was 56.6%. With a median follow-up of 14months [1-39months] local control and distant control at 1a are 70.3% and 72.6% respectively. Of the 18pts with local relapse, 13pts have recurred in-field, 1 pt at the field edge, 3pts out of field, and one in the dose gradient.
  
  
  CONCLUSIONS
  Despite high applied doses, C12 re-irradiation shows moderate side-effects, response rates even in these heavily pre-treated patients are encouraging and present a good alternative to palliative chemotherapy. Though most local recurrences occur within the high-dose area, further dose escalation should be viewed with caution.
authors: Dept of Radiation Oncology, University of Heidelberg, Germany. Electronic address: Alexandra.jensen@med.uni-heidelberg.de.
authors: Alexandra D
authors: AD
authors: Jensen
authors: Dept of Radiation Oncology, University of Heidelberg, Germany. Electronic address: melaniepoulakis@aol.com.
authors: Melanie
authors: M
authors: Poulakis
authors: Dept of Radiation Oncology, University of Heidelberg, Germany. Electronic address: Anna.nikoghosyan@helios-kliniken.de.
authors: Anna V
authors: AV
authors: Nikoghosyan
authors: Dept of Medical Physics, Heidelberg Ion Beam Therapy Center, Germany. Electronic address: Naved.chaudhri@med.uni-heidelberg.de.
authors: Naved
authors: N
authors: Chaudhri
authors: Dept of Radiation Oncology, University of Heidelberg, Germany. Electronic address: Matthias.uhl@med.uni-heidelberg.de.
authors: Matthias
authors: M
authors: Uhl
authors: Dept of Radiation Oncology, University of Heidelberg, Germany. Electronic address: m.muenter@klinikum-stuttgart.de.
authors: Marc W
authors: MW
authors: Münter
authors: Dept of Radiation Oncology, University of Heidelberg, Germany. Electronic address: Klaus.herfarth@med.uni-heidelberg.de.
authors: Klaus K
authors: KK
authors: Herfarth
authors: Dept of Radiation Oncology, University of Heidelberg, Germany. Electronic address: Juergen.debus@med.uni-heidelberg.de.
authors: Jürgen
authors: J
authors: Debus
mesh_terms: D000328:Adult; D000368:Aged; D002244:Carbon / Q000737:chemistry / Q000627:therapeutic use; D003528:Carcinoma, Adenoid Cystic / Q000532:radiotherapy*; D005260:Female; D006258:Head and Neck Neoplasms / Q000532:radiotherapy*; D063193:Heavy Ion Radiotherapy / Q000009:adverse effects / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000532:radiotherapy*; D012189:Retrospective Studies; D016879:Salvage Therapy / Q000379:methods; D055815:Young Adult
chemical_list: D002244:Carbon
keywords: Adenoid cystic carcinoma; Carbon ions; Gland tumours; Malignant salivary; Particle therapy; Re-irradiation