title: Can reduction of uncertainties in cervix cancer brachytherapy potentially improve clinical outcome?
abstract: The aim of this study was to quantify the impact of different types and magnitudes of dosimetric uncertainties in cervix cancer brachytherapy (BT) on tumour control probability (TCP) and normal tissue complication probability (NTCP) curves.
  
  
  
  A dose-response simulation study was based on systematic and random dose uncertainties and TCP/NTCP models for CTV and rectum. Large patient cohorts were simulated assuming different levels of dosimetric uncertainties. TCP and NTCP were computed, based on the planned doses, the simulated dose uncertainty, and an underlying TCP/NTCP model. Systematic uncertainties of 3-20% and random uncertainties with a 5-30% standard deviation per BT fraction were analysed.
  
  
  
  Systematic dose uncertainties of 5% lead to a 1% decrease/increase of TCP/NTCP, while random uncertainties of 10% had negligible impact on the dose-response curve at clinically relevant dose levels for target and OAR. Random OAR dose uncertainties of 30% resulted in an NTCP increase of 3-4% for planned doses of 70-80Gy EQD2.
  
  
  
  TCP is robust to dosimetric uncertainties when dose prescription is in the more flat region of the dose-response curve at doses >75Gy. For OARs, improved clinical outcome is expected by reduction of uncertainties via sophisticated dose delivery and treatment verification.
authors.affiliation: Department of Radiation Therapy, Comprehensive Cancer Center, Medical University of Vienna, Austria. Electronic address: nicole.nesvacil@meduniwien.ac.at.
authors.forename: Nicole
authors.initials: N
authors.lastname: Nesvacil
authors.affiliation: Department of Oncology, Aarhus University Hospital, Denmark.
authors.forename: Kari
authors.initials: K
authors.lastname: Tanderup
authors.affiliation: Department of Oncology, Aarhus University Hospital, Denmark.
authors.forename: Jacob C
authors.initials: JC
authors.lastname: Lindegaard
authors.affiliation: Department of Radiation Therapy, Comprehensive Cancer Center, Medical University of Vienna, Austria; Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Pötter
authors.affiliation: Department of Radiation Therapy, Comprehensive Cancer Center, Medical University of Vienna, Austria; Christian Doppler Laboratory for Medical Radiation Research for Radiation Oncology, Medical University of Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Kirisits
mesh_terms: D001918:Brachytherapy / Q000379:methods* / Q000706:statistics & numerical data*; D003198:Computer Simulation; D005260:Female; D006801:Humans; D011336:Probability; D011829:Radiation Dosage; D035501:Uncertainty; D002583:Uterine Cervical Neoplasms / Q000532:radiotherapy*
keywords: Brachytherapy; Cervix cancer; Dose response; Dosimetric uncertainties