title: Pre-treatment MRI minimum apparent diffusion coefficient value is a potential prognostic imaging biomarker in cervical cancer patients treated with definitive chemoradiation.
abstract: Diffusion Weighted (DW) Magnetic Resonance Imaging (MRI) has been studed in several cancers including cervical cancer. This study was designed to investigate the association of DW-MRI parameters with baseline clinical features and clinical outcomes (local regional control (LRC), disease free survival (DFS) and disease specific survival (DSS)) in cervical cancer patients treated with definitive chemoradiation.
  
  
  
  This was a retrospective study approved by an institutional review board that included 66 women with cervical cancer treated with definitive chemoradiation who underwent pre-treatment MRI at our institution between 2012 and 2013. A region of interest (ROI) was manually drawn by one of three radiologists with experience in pelvic imaging on a single axial CT slice encompassing the widest diameter of the cervical tumor while excluding areas of necrosis. The following apparent diffusion coefficient (ADC) values (×10(-3) mm(2)/s) were extracted for each ROI: Minimum - ADCmin, Maximum - ADCmax, Mean - ADCmean, and Standard Deviation of the ADC - ADCdev. Receiver operating characteristic (ROC) curves were built to choose the most accurate cut off value for each ADC value. Correlation between imaging metrics and baseline clinical features were evaluated using the Mann Whitney test. Confirmatory multi-variate Cox modeling was used to test associations with LRC (adjusted by gross tumor volume - GTV), DFS and DSS (both adjusted by FIGO stage). Kaplan Meyer curves were built for DFS and DSS. A p-value < 0.05 was considered significant. Women median age was 52 years (range 23-90). 67 % had FIGO stage I-II disease while 33 % had FIGO stage III-IV disease. Eighty-two percent had squamous cell cancer. Eighty-eight percent received concurrent cisplatin chemotherapy with radiation. Median EQD2 of external beam and brachytherapy was 82.2 Gy (range 74-84).
  
  
  
  Women with disease staged III-IV (FIGO) had significantly higher mean ADCmax values compared with those with stage I-II (1.806 (0.4) vs 1.485 (0.4), p = 0.01). Patients with imaging defined positive nodes also had significantly higher mean (±SD) ADCmax values compared with lymph node negative patients (1.995 (0.3) vs 1.551 (0.5), p = 0.03). With a median follow-up of 32 months (range 5-43) 11 patients (17 %) have developed recurrent disease and 8 (12 %) have died because of cervical cancer. ROC curves based on DSS showed optimal cutoffs for ADCmin (0.488 × 10(-3)), ADCmean (0.827 × 10(-3)), ADCmax (1.838 × 10(-3)) and ADCdev (0.148 × 10(-3)). ADCmin higher than the cutoff was significantly associated with worse DFS (HR = 3.632-95 % CI: 1.094-12.054; p = 0.035) and DSS (HR = 4.401-95 % CI: 1.048-18.483; p = 0.043).
  
  
  
  Pre-treatment ADCmax measured in the primary tumor may be associated with FIGO stage and lymph node status. Pre-treatment ADCmin may be a prognostic factor associated with disease-free survival and disease-specific survival in cervical cancer patients treated with definitive chemoradiation. Prospective validation of these findings is currently ongoing.
authors.affiliation: Department of Radiation Oncology, Barretos Cancer Hospital, Antenor Duarte Villela, 1331, Barretos, Sao Paulo, 14784-400, Brazil. dgmarconi@gmail.com.
authors.forename: Daniel Grossi
authors.initials: DG
authors.lastname: Marconi
authors.affiliation: Department of Gynecology Oncology, Barretos Cancer Hospital, Barretos, Sao Paulo, Brazil.
authors.forename: Jose Humberto Tavares Guerreiro
authors.initials: JH
authors.lastname: Fregnani
authors.affiliation: Department of Radiology, Barretos Cancer Hospital, Barretos, Sao Paulo, Brazil.
authors.forename: Rodrigo Ribeiro
authors.initials: RR
authors.lastname: Rossini
authors.affiliation: Department of Radiology, Barretos Cancer Hospital, Barretos, Sao Paulo, Brazil.
authors.forename: Ana Karina Borges Junqueira
authors.initials: AK
authors.lastname: Netto
authors.affiliation: Department of Radiology, Barretos Cancer Hospital, Barretos, Sao Paulo, Brazil.
authors.forename: Fabiano Rubião
authors.initials: FR
authors.lastname: Lucchesi
authors.affiliation: Department of Gynecology Oncology, Barretos Cancer Hospital, Barretos, Sao Paulo, Brazil.
authors.forename: Audrey Tieko
authors.initials: AT
authors.lastname: Tsunoda
authors.affiliation: Department of Radiation Oncology, University of California Los Angeles, Los Angeles, CA, USA.
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kamrava
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D059248:Chemoradiotherapy; D038524:Diffusion Magnetic Resonance Imaging / Q000379:methods*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models; D012372:ROC Curve; D012189:Retrospective Studies; D002583:Uterine Cervical Neoplasms / Q000000981:diagnostic imaging* / Q000401:mortality* / Q000628:therapy*; D055815:Young Adult
keywords: Cervical cancer; Chemoradiation; Diffusion weighted imaging; MRI