title: A multicentre comparison of the dosimetric impact of inter- and intra-fractional anatomical variations in fractionated cervix cancer brachytherapy.
abstract: OBJECTIVE
  To compare the dosimetric impact of organ and target variations relative to the applicator for intracavitary brachytherapy by a multicentre analysis with different application techniques and fractionation schemes.
  
  
  METHODS
  DVH data from 363 image/contour sets (120 patients, 6 institutions) were included for 1-6 fractions per patient, with imaging intervals ranging from several hours to ∼20 days. Variations between images acquired within one (intra-application) or between consecutive applicator insertions (inter-application) were evaluated. Dose plans based on a reference MR or CT image series were superimposed onto subsequent image sets and D(2cm(3)) for the bladder, rectum and sigmoid and D(90) for HR CTV were recorded.
  
  
  RESULTS
  For the whole sample, the systematic dosimetric variations for all organs at risk, i.e. mean variations of D(2cm(3)), were found to be minor (<5%), while random variations, i.e. standard deviations were found to be high due to large variations in individual cases. The D(2cm(3)) variations (mean±1SD) were 0.6±19.5%, 4.1±21.7% and 1.6±26.8%, for the bladder, rectum and sigmoid. For HR CTV, the variations of D90 were found to be -1.1±13.1% for the whole sample. Grouping of the results by intra- and inter-application variations showed that random uncertainties for bladder and sigmoid were 3-7% larger when re-implanting the applicator for individual fractions. No statistically significant differences between the two groups were detected in dosimetric variations for the HR CTV. Using 20% uncertainty of physical dose for OAR and 10% for HR CTV, the effects on total treatment dose for a 4 fraction HDR schedule at clinically relevant dose levels were found to be 4-8 Gy EQD2 for OAR and 3 Gy EQD2 for HR CTV.
  
  
  CONCLUSIONS
  Substantial variations occur in fractionated cervix cancer BT with higher impact close to clinical threshold levels. The treatment approach has to balance uncertainties for individual cases against the use of repetitive imaging, adaptive planning and dose delivery.
authors.affiliation: Department of Radiotherapy and Oncology, Comprehensive Cancer Center, Medical University of Vienna, Austria. nicole.nesavcil@meduniwien.ac.at
authors.forename: Nicole
authors.initials: N
authors.lastname: Nesvacil
authors.forename: Kari
authors.initials: K
authors.lastname: Tanderup
authors.forename: Taran P
authors.initials: TP
authors.lastname: Hellebust
authors.forename: Astrid
authors.initials: A
authors.lastname: De Leeuw
authors.forename: Stefan
authors.initials: S
authors.lastname: Lang
authors.forename: Sandy
authors.initials: S
authors.lastname: Mohamed
authors.forename: Swamidas V
authors.initials: SV
authors.lastname: Jamema
authors.forename: Clare
authors.initials: C
authors.lastname: Anderson
authors.forename: Richard
authors.initials: R
authors.lastname: Pötter
authors.forename: Christian
authors.initials: C
authors.lastname: Kirisits
mesh_terms: D001918:Brachytherapy / Q000379:methods*; D019583:Dose Fractionation, Radiation; D005260:Female; D006801:Humans; D011879:Radiotherapy Dosage; D061089:Radiotherapy, Image-Guided / Q000379:methods*; D047368:Tumor Burden; D002583:Uterine Cervical Neoplasms / Q000473:pathology / Q000532:radiotherapy*