title: Evaluation of tumor shape variability in head-and-neck cancer patients over the course of radiation therapy using implanted gold markers.
abstract: OBJECTIVE
  This study quantifies tumor shape variability in head-and-neck cancer patients during radiation therapy using implanted markers.
  
  
  METHODS
  Twenty-seven patients with oropharyngeal tumors treated with (chemo)radiation were included. Helical gold markers (0.35 × 2 mm, 3-10/patient, average 6) were implanted around the tumor. Markers were identified on planning computed tomography (CT) and daily cone beam CT (CBCT). After bony anatomy registration, the daily vector length on CBCT in reference to the planning CT and daily marker movement perpendicular to the gross tumor volume (GTV) surface at planning CT (d(normal)) of each marker were analyzed. Time trends were assessed with linear regression of the <d(normal)>(markers). In 2 patients, 2 markers were implanted in normal tissue to evaluate migration by measuring intermarker distances.
  
  
  RESULTS
  Marker implantation was feasible without complications. Three-dimensional vectors (4827 measurements, mean 0.23 cm, interquartile ratio 0.24 cm) were highest in base of tongue sublocalization (P<.001) and bulky tumors (vectors exceeded 0.5 cm in 5.7% [0-20 mL], 12.0% [21-40 mL], and 21.7% [≥ 41 mL], respectively [P<.001] of measurements). The measured inward time trend in 11/27 patients correlated with the visual observed marker pattern. In patients with an outward trend (5/27) or no trend (11/27), visual observation showed predominantly an inhomogeneous pattern. Remarkably, in 6 patients, outward marker movement was observed in the posterior pharyngeal wall. The difference in distance between normal tissue markers (1 SD) was 0.05-0.06 cm without time trend, indicating that implanted markers did not migrate.
  
  
  CONCLUSIONS
  During head-and-neck radiation therapy, normal tissue markers remained stable. Changes in position of tumor markers depended on sublocalization and tumor volume. Large differences in marker patterns between patients as well as within patients were observed. Based on our study, the cranial and caudal border in the posterior pharyngeal wall are at highest risk to be covered insufficiently. Furthermore, implanted markers could help identify patients with an actual shrinkage of the GTV who might benefit from mid-radiation therapy redelineation to reduce toxicity.
authors.affiliation: Department of Radiotherapy, Netherlands Cancer Institute-Antoni van Leeuwenhoek Hospital, Amsterdam, Netherlands. o.vrieze@nki.nl
authors.forename: Olga
authors.initials: O
authors.lastname: Hamming-Vrieze
authors.forename: Simon Robert
authors.initials: SR
authors.lastname: van Kranen
authors.forename: Suzanne
authors.initials: S
authors.lastname: van Beek
authors.forename: Wilma
authors.initials: W
authors.lastname: Heemsbergen
authors.forename: Marcel
authors.initials: M
authors.lastname: van Herk
authors.forename: Michiel Wilhelmus Maria
authors.initials: MW
authors.lastname: van den Brekel
authors.forename: Jan-Jakob
authors.initials: JJ
authors.lastname: Sonke
authors.forename: Coenraad Robert Nico
authors.initials: CR
authors.lastname: Rasch
mesh_terms: D059925:Anatomic Landmarks; D059248:Chemoradiotherapy / Q000379:methods; D054893:Cone-Beam Computed Tomography; D057918:Fiducial Markers; D006046:Gold; D006801:Humans; D016014:Linear Models; D009068:Movement; D009959:Oropharyngeal Neoplasms / Q000000981:diagnostic imaging / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy*; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D014057:Tomography, X-Ray Computed / Q000379:methods; D047368:Tumor Burden / Q000528:radiation effects*
chemical_list: D006046:Gold