title: Origin of tumor recurrence after intensity modulated radiation therapy for oropharyngeal squamous cell carcinoma.
abstract: OBJECTIVE
  To model locoregional recurrences of oropharyngeal squamous cell carcinomas (OSCC) treated with primary intensity modulated radiation therapy (IMRT) in order to find the origins from which recurrences grow and relate their location to original target volume borders.
  
  
  METHODS
  This was a retrospective analysis of OSCC treated with primary IMRT between January 2002 and December 2009. Locoregional recurrence volumes were delineated on diagnostic scans and coregistered rigidly with treatment planning computed tomography scans. Each recurrence was analyzed with two methods. First, overlapping volumes of a recurrence and original target were measured ('volumetric approach') and assessed as 'in-field', 'marginal', or 'out-field'. Then, the center of mass (COM) of a recurrence volume was assumed as the origin from where a recurrence expanded, the COM location was compared with original target volume borders and assessed as 'in-field', 'marginal', or 'out-field'.
  
  
  RESULTS
  One hundred thirty-one OSCC were assessed. For all patients alive at the end of follow-up, the mean follow-up time was 40 months (range, 12-83 months); 2 patients were lost to follow-up. The locoregional recurrence rate was 27%. Of all recurrences, 51% were local, 23% were regional, and 26% had both local and regional recurrences. Of all recurrences, 74% had imaging available for assessment. Regarding volumetric analysis of local recurrences, 15% were in-field gross tumor volume (GTV), and 65% were in-field clinical tumor volume (CTV). Using the COM approach, we found that 70% of local recurrences were in-field GTV and 90% were in-field CTV. Of the regional recurrences, 25% were volumetrically in-field GTV, and using the COM approach, we found 54% were in-field GTV. The COM of local out-field CTV recurrences were maximally 16 mm outside CTV borders, whereas for regional recurrences, this was 17 mm.
  
  
  CONCLUSIONS
  The COM model is practical and specific for recurrence assessment. Most recurrences originated in the GTV. This suggests radioresistance in certain tumor parts.
authors.affiliation: Department of Radiotherapy, University Medical Center Utrecht, Utrecht, The Netherlands.
authors.forename: Sawan A S
authors.initials: SA
authors.lastname: Raktoe
authors.forename: Homan
authors.initials: H
authors.lastname: Dehnad
authors.forename: Cornelis P J
authors.initials: CP
authors.lastname: Raaijmakers
authors.forename: Weibel
authors.initials: W
authors.lastname: Braunius
authors.forename: Chris H J
authors.initials: CH
authors.lastname: Terhaard
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000000981:diagnostic imaging* / Q000473:pathology / Q000532:radiotherapy* / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D009364:Neoplasm Recurrence, Local / Q000000981:diagnostic imaging* / Q000473:pathology; D009959:Oropharyngeal Neoplasms / Q000000981:diagnostic imaging* / Q000473:pathology / Q000532:radiotherapy*; D011836:Radiation Tolerance; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D050397:Radiotherapy, Intensity-Modulated; D012189:Retrospective Studies; D016019:Survival Analysis; D014057:Tomography, X-Ray Computed / Q000379:methods; D047368:Tumor Burden