Pre-treatment MRI minimum apparent diffusion coefficient value is a potential prognostic imaging biomarker in cervical cancer patients treated with definitive chemoradiation

Abstract

Background

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.

Methods

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 - ADC _min, Maximum - ADC _max, Mean - ADC _mean, and Standard Deviation of the ADC - ADC _dev. 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).

Results

Women with disease staged III-IV (FIGO) had significantly higher mean ADC _max 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) ADC _max 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 ADC _min (0.488 × 10 ⁻³), ADC _mean (0.827 × 10 ⁻³), ADC _max (1.838 × 10 ⁻³) and ADC _dev (0.148 × 10 ⁻³). ADC _min 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).

Conclusion

Pre-treatment ADC _max measured in the primary tumor may be associated with FIGO stage and lymph node status. Pre-treatment ADC _min 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.