title: Increasing treatment accuracy for cervical cancer patients using correlations between bladder-filling change and cervix-uterus displacements: proof of principle.
abstract: OBJECTIVE
  To investigate application of pre-treatment established correlations between bladder-filling changes and cervix-uterus displacements in adaptive therapy.
  
  
  METHODS
  Thirteen cervical cancer patients participated in this prospective study. Pre-treatment, and after delivery of 40 Gy, a full bladder CT-scan was acquired, followed by voiding the bladder and acquisition of 4 other 3D scans in a 1h period with a naturally filling bladder (variable bladder filling CT-scans, VBF-scans). For the pre-treatment VBF-scans, linear correlations between bladder volume change and displacements of the tip of the uterus (ToU) and the center of mass (CoM) of markers implanted in the fornices of the vagina relative to the full bladder planning scan were established. Prediction accuracy of these correlation models was assessed by comparison with actual displacements in CT-scans, both pre-treatment and after 40 Gy. Inter-fraction ToU and marker-CoM displacements were derived from the established correlations and twice-weekly performed in-room bladder volume measurements, using a 3D ultrasound scanner.
  
  
  RESULTS
  Target displacement in VBF-scans ranged from up to 65 mm in a single direction to almost 0mm, depending on the patient. For pre-treatment VBF-scans, the linear correlation models predicted the mean 3D position change for the ToU of 26.1 mm±10.8 with a residual of only 2.2 mm±1.7. For the marker-CoM, the 8.4 mm±5.3 mean positioning error was predicted with a residual of 0.9 mm±0.7. After 40Gy, the mean ToU displacement was 26.8 mm±15.8, while prediction based on the pre-treatment correlation models yielded a mean residual error of 9.0 mm±3.7. Target positioning errors in the fractioned treatments were very large, especially for the ToU (-18.5mm±11.2 for systematic errors in SI-direction).
  
  
  CONCLUSIONS
  Pre-treatment acquired VBF-scans may be used to substantially enhance treatment precision of cervical cancer patients. Application in adaptive therapy is promising and warrants further investigation. For highly conformal (IMRT) treatments, the use of a full bladder drinking protocol results in unacceptably large systematic set-up errors.
authors.affiliation: Department of Radiation Oncology, Erasmus MC-Daniel den Hoed Cancer Center, Rotterdam, The Netherlands. r.ahmad@erasmusmc.nl
authors.forename: Rozilawati
authors.initials: R
authors.lastname: Ahmad
authors.forename: Mischa S
authors.initials: MS
authors.lastname: Hoogeman
authors.forename: Maria
authors.initials: M
authors.lastname: Bondar
authors.forename: V
authors.initials: V
authors.lastname: Dhawtal
authors.forename: Sandra
authors.initials: S
authors.lastname: Quint
authors.forename: Ilse
authors.initials: I
authors.lastname: De Pree
authors.forename: Jan Willem
authors.initials: JW
authors.lastname: Mens
authors.forename: Ben J M
authors.initials: BJ
authors.lastname: Heijmen
mesh_terms: D000328:Adult; D000368:Aged; D002584:Cervix Uteri / Q000000981:diagnostic imaging*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008875:Middle Aged; D009929:Organ Size; D011859:Radiography; D011879:Radiotherapy Dosage; D001743:Urinary Bladder / Q000000981:diagnostic imaging*; D002583:Uterine Cervical Neoplasms / Q000000981:diagnostic imaging / Q000532:radiotherapy*