title: Combined intensity-modulated radiotherapy plus raster-scanned carbon ion boost for advanced adenoid cystic carcinoma of the head and neck results in superior locoregional control and overall survival.
abstract: BACKGROUND
  Local control in patients with adenoid cystic carcinoma (ACC) of the head and neck remains a challenge because of the relative radioresistance of these tumors. This prospective carbon ion pilot project was designed to evaluate the efficacy and toxicity of intensity-modulated radiotherapy (IMRT) plus carbon ion (C12) boost (C12 therapy). The authors present the first analysis of long-term outcomes of raster-scanned C12 therapy compared with modern photon techniques.
  
  
  METHODS
  Patients with inoperable or subtotally resected ACC received C12 therapy within the pilot project. Whenever C12 was not available, patients were offered IMRT or fractionated stereotactic radiotherapy (FSRT). Patients received either C12 therapy at a C12 dose of 3 Gray equivalents (GyE) per fraction up to 18 GyE followed by 54 Gray (Gy) of IMRT or IMRT up to a median total dose of 66 Gy. Toxicity was evaluated according to version 3 of the Common Toxicity Terminology for Adverse Events. Locoregional control (LC), progression-free survival (PFS), and overall survival (OS) were analyzed using the Kaplan-Meier method.
  
  
  RESULTS
  Fifty-eight patients received C12 therapy, and 37 received photons (IMRT or FSRT). The median follow-up was 74 months in the C12 group and 63 months in the photon group. Overall, 90% of patients in the C12 group and 94% of those in the photon group had T4 tumors; and the most common disease sites were paranasal sinus, parotid with skull base invasion, and nasopharynx. LC, PFS, and OS at 5 years were significantly higher in the C12 group (59.6%, 48.4%, 76.5%, respectively) compared with the photon group (39.9%, 27%, and 58.7%, respectively). There was no significant difference between patients who had subtotally resected and inoperable ACC.
  
  
  CONCLUSIONS
  C12 therapy resulted in superior LC, PFS, and OS without a significant difference between patients with inoperable and partially resected ACC. Extensive and morbid resections in patients with advanced ACC may need to be reconsidered. The most common site of locoregional recurrence remains in field, and further C12 dose escalation should be evaluated.
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Alexandra D
authors.initials: AD
authors.lastname: Jensen
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Anna V
authors.initials: AV
authors.lastname: Nikoghosyan
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Melanie
authors.initials: M
authors.lastname: Poulakis
authors.affiliation: Medical Informatics and Regulatory Affairs, Heidelberg Ion Beam Therapy Center, Heidelberg, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Höss
authors.affiliation: Heidelberg Ion Beam Therapy Center, Heidelberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Haberer
authors.affiliation: Heidelberg Ion Beam Therapy Center, Heidelberg, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Jäkel
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Marc W
authors.initials: MW
authors.lastname: Münter
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Daniela
authors.initials: D
authors.lastname: Schulz-Ertner
authors.affiliation: Molecular Radiation Oncology, German Cancer Research Center, Heidelberg, Germany.
authors.forename: Peter E
authors.initials: PE
authors.lastname: Huber
authors.affiliation: Department of Radiation Oncology, University of Heidelberg, Heidelberg, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Debus
mesh_terms: D000328:Adult; D000368:Aged; D003528:Carcinoma, Adenoid Cystic / Q000401:mortality / Q000532:radiotherapy*; D018572:Disease-Free Survival; D006258:Head and Neck Neoplasms / Q000401:mortality / Q000532:radiotherapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D050397:Radiotherapy, Intensity-Modulated; D016896:Treatment Outcome; D055815:Young Adult
keywords: adenoid cystic carcinoma; carbon ion therapy; carbon ions; fractionated stereotactic radiotherapy; intensity-modulated radiotherapy; long-term results; malignant salivary gland tumors; raster scanning