title: Effect of tumor dose, volume and overall treatment time on local control after radiochemotherapy including MRI guided brachytherapy of locally advanced cervical cancer.
abstract: Currently, there is no consensus on dose prescription in image guided adaptive brachytherapy (IGABT) in locally advanced cervical cancer. The purpose of this study was to provide evidence based recommendations for tumor dose prescription based on results from a multi-center patient series (retroEMBRACE).
  
  
  
  This study analyzed 488 locally advanced cervical cancer patients treated with external beam radiotherapy±chemotherapy combined with IGABT. Brachytherapy contouring and reporting was according to ICRU/GEC-ESTRO recommendations. The Cox Proportional Hazards model was applied to analyze the effect on local control of dose-volume metrics as well as overall treatment time (OTT), dose rate, chemotherapy, and tumor histology.
  
  
  
  With a median follow up of 46months, 43 local failures were observed. Dose (D90) to the High Risk Clinical Target Volume (CTVHR) (p=0.022, HR=0.967 per Gy) was significant for local control, whereas increasing CTVHRvolume (p=0.004, HR=1.017 per cm3), and longer OTT (p=0.004, HR=1.023 per day) were associated with worse local control. Histology (p=0.084), chemotherapy (p=0.49) and dose rate (p=1.00) did not have significant impact on local control. Separate analyses according to stage of disease showed that dose to CTVHR, residual gross tumor volume (GTVres), and Intermediate Risk CTV (CTVIR) has significant impact on local control.
  
  
  
  CTVHRdose of ⩾85Gy (D90) delivered in 7weeks provides 3-year local control rates of >94% in limited size CTVHR(20cm3), >93% in intermediate size (30cm3) and >86% in large size (70cm3) CTVHR. CTVIRand GTVresdose of ⩾60Gy and ⩾95Gy (D98) leads to similar local control. A dose of 5Gy (CTVHR) is required to compensate an increase of OTT by one week. Increased CTVHRvolume by 10cm3requires additional 5Gy for equivalent local control.
authors.affiliation: Department of Oncology, Aarhus University Hospital, Denmark. Electronic address: karitand@rm.dk.
authors.forename: Kari
authors.initials: K
authors.lastname: Tanderup
authors.affiliation: Department of Oncology, Aarhus University Hospital, Denmark.
authors.forename: Lars Ulrik
authors.initials: LU
authors.lastname: Fokdal
authors.affiliation: Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Austria.
authors.forename: Alina
authors.initials: A
authors.lastname: Sturdza
authors.affiliation: Radiation Oncology Department, Gustave Roussy Cancer Campus Grand Paris, Villejuif, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Haie-Meder
authors.affiliation: Radiation Oncology Department, Gustave Roussy Cancer Campus Grand Paris, Villejuif, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Mazeron
authors.affiliation: Department of Radiation-Oncology, University Hospitals of Leuven, Belgium.
authors.forename: Erik
authors.initials: E
authors.lastname: van Limbergen
authors.affiliation: Department of Radiotherapy, University Medical Center Utrecht, The Netherlands.
authors.forename: Ina
authors.initials: I
authors.lastname: Jürgenliemk-Schulz
authors.affiliation: Department of Radiation Oncology, National Center for Cancer Care and Research, Doha, Qatar; Division of Radiotherapy, National Institute of Oncology, Ljubljana, Slovenia.
authors.forename: Primoz
authors.initials: P
authors.lastname: Petric
authors.affiliation: Mount Vernon Cancer Centre, Northwood, United Kingdom.
authors.forename: Peter
authors.initials: P
authors.lastname: Hoskin
authors.affiliation: Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Austria.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Dörr
authors.affiliation: Greenebaum Cancer Center and Department of Epidemiology and Public Health, University of Maryland School of Medicine, Baltimore, USA.
authors.forename: Søren M
authors.initials: SM
authors.lastname: Bentzen
authors.affiliation: Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Austria.
authors.forename: Christian
authors.initials: C
authors.lastname: Kirisits
authors.affiliation: Department of Oncology, Aarhus University Hospital, Denmark.
authors.forename: Jacob Christian
authors.initials: JC
authors.lastname: Lindegaard
authors.affiliation: Department of Radiation Oncology, Comprehensive Cancer Center, Medical University of Vienna, Austria.
authors.forename: Richard
authors.initials: R
authors.lastname: Pötter
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001918:Brachytherapy / Q000379:methods*; D059248:Chemoradiotherapy / Q000379:methods; D019583:Dose Fractionation, Radiation; D019317:Evidence-Based Medicine / Q000379:methods; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009367:Neoplasm Staging; D011879:Radiotherapy Dosage; D011880:Radiotherapy Planning, Computer-Assisted / Q000379:methods; D061089:Radiotherapy, Image-Guided / Q000379:methods*; D013997:Time Factors; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000000981:diagnostic imaging / Q000473:pathology / Q000532:radiotherapy*; D055815:Young Adult
keywords: Cervical cancer; Dose effect; Image guided brachytherapy; Local control; Overall treatment time