title: Dysphagia and aspiration after chemoradiotherapy for head-and-neck cancer: which anatomic structures are affected and can they be spared by IMRT?
abstract: OBJECTIVE
  To identify the anatomic structures whose damage or malfunction cause late dysphagia and aspiration after intensive chemotherapy and radiotherapy (RT) for head-and-neck cancer, and to explore whether they can be spared by intensity-modulated RT (IMRT) without compromising target RT.
  
  
  METHODS
  A total of 26 patients receiving RT concurrent with gemcitabine, a regimen associated with a high rate of late dysphagia and aspiration, underwent prospective evaluation of swallowing with videofluoroscopy (VF), direct endoscopy, and CT. To assess whether the VF abnormalities were regimen specific, they were compared with the VF findings of 6 patients presenting with dysphagia after RT concurrent with high-dose intra-arterial cisplatin. The anatomic structures whose malfunction was likely to cause each of the VF abnormalities common to both regimens were determined by literature review. Pre- and posttherapy CT scans were reviewed for evidence of posttherapy damage to each of these structures, and those demonstrating posttherapy changes were deemed dysphagia/aspiration-related structures (DARS). Standard three-dimensional (3D) RT, standard IMRT (stIMRT), and dysphagia-optimized IMRT (doIMRT) plans in which sparing of the DARS was included in the optimization cost function, were produced for each of 20 consecutive patients with advanced head-and-neck cancer.
  
  
  RESULTS
  The posttherapy VF abnormalities common to both regimens included weakness of the posterior motion of the base of tongue, prolonged pharyngeal transit time, lack of coordination between the swallowing phases, reduced elevation of the larynx, and reduced laryngeal closure and epiglottic inversion, contributing to a high rate of aspiration. The anatomic structures whose malfunction was the likely cause of each of these abnormalities, and that also demonstrated anatomic changes after RT concurrent with gemcitabine doses associated with dysphagia and aspiration, were the pharyngeal constrictor muscles (median thickness near midline 2.5 mm before therapy vs. 7 mm after therapy; p = 0.001), the supraglottic larynx (median thickness, 2 mm before therapy vs. 4 mm after therapy; p < 0.001), and, similarly, the glottic larynx. The constrictors and the glottic and supraglottic larynx were, therefore, deemed the DARS. The lowest maximal dose delivered to a stricture volume was 50 Gy. Reducing the volumes of the DARS receiving > or =50 Gy (V(50)) was, therefore, a planning and evaluation goal. Compared with the 3D plans, stIMRT reduced the V(50) of the pharyngeal constrictors by 10% on average (range, 0-36%, p < 0.001), and doIMRT reduced these volumes further, by an additional 10% on average (range, 0-38%; p <0.001). The V(50) of the larynx (glottic + supraglottic) was reduced marginally by stIMRT compared with 3D (by 7% on average, range, 0-56%; p = 0.054), and doIMRT reduced these volumes by an additional 11%, on average (range, 0-41%; p = 0.002). doIMRT reduced laryngeal V(50) compared with 3D, by 18% on average (range 0-61%; p = 0.001). Certain target delineation rules facilitated sparing of the DARS by IMRT. The maximal DARS doses were not reduced by IMRT because of their partial overlap with the targets. stIMRT and doIMRT did not differ in target doses, parotid gland mean dose, spinal cord, or nonspecified tissue maximal dose.
  
  
  CONCLUSIONS
  The structures whose damage may cause dysphagia and aspiration after intensive chemotherapy and RT are the pharyngeal constrictors and the glottic and supraglottic larynx. Compared with 3D-RT, moderate sparing of these structures was achieved by stIMRT, and an additional benefit, whose extent varied among the patients, was gained by doIMRT, without compromising target doses. Clinical validation is required to determine whether the dosimetric gains are translated into clinical ones.
authors.affiliation: Department of Radiation Oncology, University of Michigan, Ann Arbor, MI 48109, USA. eisbruch@umich.edu
authors.forename: Avraham
authors.initials: A
authors.lastname: Eisbruch
authors.forename: Marco
authors.initials: M
authors.lastname: Schwartz
authors.forename: Coen
authors.initials: C
authors.lastname: Rasch
authors.forename: Karen
authors.initials: K
authors.lastname: Vineberg
authors.forename: Eugene
authors.initials: E
authors.lastname: Damen
authors.forename: Corina J
authors.initials: CJ
authors.lastname: Van As
authors.forename: Robin
authors.initials: R
authors.lastname: Marsh
authors.forename: Frank A
authors.initials: FA
authors.lastname: Pameijer
authors.forename: Alfons J M
authors.initials: AJ
authors.lastname: Balm
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects; D003131:Combined Modality Therapy / Q000379:methods; D003679:Deglutition; D003680:Deglutition Disorders / Q000209:etiology / Q000517:prevention & control*; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D007013:Hypopharynx / Q000187:drug effects / Q000528:radiation effects; D007091:Image Processing, Computer-Assisted; D014066:Palatine Tonsil / Q000187:drug effects / Q000528:radiation effects; D010609:Pharyngeal Muscles / Q000187:drug effects / Q000528:radiation effects; D011015:Pneumonia, Aspiration / Q000209:etiology / Q000517:prevention & control*; D011446:Prospective Studies; D020266:Radiotherapy, Conformal / Q000379:methods*; D014059:Tongue / Q000187:drug effects / Q000528:radiation effects; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine