title: Pulsed-dose rate image-guided adaptive brachytherapy in cervical cancer: Dose-volume effect relationships for the rectum and bladder.
abstract: OBJECTIVE
  To establish dose-volume effect correlations for late bladder and rectum side effects in patients treated for locally advanced cervical cancer with concomitant chemoradiation followed by pulsed-dose rate image-guided adaptive brachytherapy.
  
  
  METHODS
  The dosimetric data, converted in 2 Gy equivalent, from 217 patients were confronted to late morbidity defined as any event lasting or occurring 90 days after treatment initiation. Toxicity was assessed using the CTC-AE 3.0. Probit analyses and Log rank tests were performed to assess relationships.
  
  
  RESULTS
  One hundred and sixty-one urinary and 58 rectal events were reported, affecting 98 (45.1%) and 51 (23.5%) patients, respectively. Cumulative incidences for grade 2-4 bladder and rectal morbidity were 24.3% and 9.6% at 3 years, respectively. Significant relationships were observed between grade 2-4 and 3-4 events and D0.1cm(3) and D2 cm(3) for the bladder and between grade 1-4 and 2-4 event probability and rectal D2 cm(3). The effective doses for 10% grade 2-4 morbidity were 65.3 Gy (59.8-81.3), and 55.4 Gy (15.7-63.6), respectively, for the rectum and bladder. Without considering urinary and rectal incontinence, for which the pertinence of correlating them with D2 cm(3) is questionable, ED10 were 68.5 Gy (62.9-110.6) and 65.5 Gy (51.4-71.6 Gy). When sorting patients according to D2 cm(3) levels, patients with high D2 cm(3) had significantly lower morbidity free survival rates for grade 1-4 and 2-4 urinary and rectal morbidity.
  
  
  CONCLUSIONS
  Significant dose-volume effect relationships were demonstrated between the modern dosimetric parameters and the occurrence of late rectal and urinary morbidity in patients treated with pulsed-dose-rate brachytherapy. Further studies are required to refine these relationships according to clinical cofactors, such as comorbidities.
authors.affiliation: Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France; Molecular Radiotherapy, INSERM 1030, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: Renaud.mazeron@gustaveroussy.fr.
authors.forename: Renaud
authors.initials: R
authors.lastname: Mazeron
authors.affiliation: Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Maroun
authors.affiliation: Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Pauline
authors.initials: P
authors.lastname: Castelnau-Marchand
authors.affiliation: Medical Physics, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Dumas
authors.affiliation: Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Eleonor Rivin
authors.initials: ER
authors.lastname: del Campo
authors.affiliation: Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Kim
authors.initials: K
authors.lastname: Cao
authors.affiliation: Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Andrea
authors.initials: A
authors.lastname: Slocker-Escarpa
authors.affiliation: Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Rodrigue
authors.initials: R
authors.lastname: M'Bagui
authors.affiliation: Medical Physics, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Martinetti
authors.affiliation: Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Tailleur
authors.affiliation: Medical Physics, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Alain
authors.initials: A
authors.lastname: Guemnie-Tafo
authors.affiliation: Gynecologic Surgery, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Morice
authors.affiliation: Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France; Molecular Radiotherapy, INSERM 1030, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Chargari
authors.affiliation: Molecular Radiotherapy, INSERM 1030, Gustave Roussy Cancer Campus, Villejuif, France; Medical Physics, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Lefkopoulos
authors.affiliation: Radiation Oncology, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Haie-Meder
mesh_terms: D000328:Adult; D000368:Aged; D001918:Brachytherapy / Q000009:adverse effects / Q000379:methods*; D005260:Female; D006801:Humans; D008875:Middle Aged; D011879:Radiotherapy Dosage; D061089:Radiotherapy, Image-Guided / Q000379:methods*; D012007:Rectum / Q000528:radiation effects*; D001743:Urinary Bladder / Q000528:radiation effects*; D002583:Uterine Cervical Neoplasms / Q000532:radiotherapy*
keywords: Cervix cancer; Dose–volume parameters; Image-guided adaptive brachytherapy; Morbidity; Normal tissue complication probability