title: Impact of treatment time and dose escalation on local control in locally advanced cervical cancer treated by chemoradiation and image-guided pulsed-dose rate adaptive brachytherapy.
abstract: OBJECTIVE
  To report the prognostic factors for local control in patients treated for locally advanced cervical cancer with image guided pulsed-dose rate brachytherapy.
  
  
  METHODS
  Patients treated with curative intent by a combination of external beam radiotherapy and pulsed-dose rate brachytherapy were selected. Local failure was defined as any relapse in the cervix, vagina, parametria, or uterus during follow-up. Prognostic factors were selected based on log rank tests and then analyzed with a Cox model. Dose/effect correlations were performed using the probit model.
  
  
  RESULTS
  Two hundred and twenty-five patients treated from 2006 to 2011 were included. According to the FIGO classification, 29% were stage IB, 58% stage II, 10% stage III, and 3% stage IVA; 95% received concomitant chemotherapy. Thirty patients were considered having incomplete response or local failure. Among the selected parameters, D90 for HR-CTV, D90 for IR-CTV, the overall treatment time, the TRAK, and the HR-CTV volume appeared significantly correlated with local control in univariate analysis. In multivariate analysis, overall treatment time >55days and HR-CTV volume >30cm(3) appeared as independent. The probit analysis showed significant correlations between the D90 for both CTVs, and the probability of achieving local control (p=0.008 and 0.024). The thresholds to reach to warrant a probability of 90% of local control were 85Gy to the D90 of the HR-CTV and 75Gy to 90% of the IR-CTV (in 2Gy equivalent, α/β=10). To warrant the same local control rate, the D90 HR-CTV should be significantly increased in stage III-IV tumors, in case of HR-CTV >30cm(3), excessive treatment time, or tumor width at diagnosis >5cm (97, 92, 105, and 92Gy respectively).
  
  
  CONCLUSIONS
  Overall treatment time and HR-CTV volume were independent prognostic factors for local control. The D90 for HR and IR CTV were significantly correlated with local control, and D90 HR-CTV should be adapted to clinical criteria.
authors.affiliation: Radiation Therapy, Gustave Roussy Cancer Campus, Villejuif, France; Molecular Radiotherapy, UMR1030, Gustave Roussy Cancer Campus, Villejuif, France. Electronic address: renaud.mazeron@gustaveroussy.fr.
authors.forename: Renaud
authors.initials: R
authors.lastname: Mazeron
authors.affiliation: Radiation Therapy, 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 Therapy, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Eleonor Rivin
authors.initials: ER
authors.lastname: del Campo
authors.affiliation: Radiation Therapy, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Léopold Kamsu
authors.initials: LK
authors.lastname: Kom
authors.affiliation: Medical Physics, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Florent
authors.initials: F
authors.lastname: Martinetti
authors.affiliation: Radiation Therapy, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: George
authors.initials: G
authors.lastname: Farha
authors.affiliation: Radiation Therapy, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Tailleur
authors.affiliation: Gynecologic Surgery, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Morice
authors.affiliation: Radiation Therapy, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Chargari
authors.affiliation: Molecular Radiotherapy, UMR1030, 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 Therapy, Gustave Roussy Cancer Campus, Villejuif, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Haie-Meder
mesh_terms: D001918:Brachytherapy / Q000379:methods*; D016190:Carboplatin / Q000627:therapeutic use*; D059248:Chemoradiotherapy; D002945:Cisplatin / Q000627:therapeutic use*; D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D012189:Retrospective Studies; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*
chemical_list: D016190:Carboplatin; D002945:Cisplatin
keywords: Cervical cancer; D90; Dose–effect correlation; Image-guided adaptive brachytherapy; Local control; Treatment time