a b s t r a c tPurpose: The aims of this study are to evaluate the stability of radiomic features from Apparent Diffusion Coefficient (ADC) maps of cervical cancer with respect to: (1) reproducibility in inter-observer delineation, and (2) image pre-processing (normalization/quantization) prior to feature extraction. Materials and methods: Two observers manually delineated the tumor on ADC maps derived from pretreatment diffusion-weighted Magnetic Resonance imaging of 81 patients with FIGO stage IB-IVA cervical cancer. First-order, shape, and texture features were extracted from the original and filtered images considering 5 different normalizations (four taken from the available literature, and one based on urine ADC) and two different quantization techniques (fixed-bin widths from 0.05 to 25, and fixed-bin count). Stability of radiomic features was assessed using intraclass correlation coefficient (ICC): poor (ICC < 0.75); good (0.75 ICC 0.89), and excellent (ICC ! 0.90). Dependencies of the features with tumor volume were assessed using Spearman's correlation coefficient (q). Results: The approach using urine-normalized values together with a smaller bin width (0.05) was the most reproducible (428/552, 78% features with ICC ! 0.75); the fixed-bin count approach was the least (215/552, 39% with ICC ! 0.75). Without normalization, using a fixed bin width of 25, 348/552 (63%) of features had an ICC ! 0.75. Overall, 26% (range 25-30%) of the features were volume-dependent (q ! 0.6). None of the volume-independent shape features were found to be reproducible. Conclusion: Applying normalization prior to features extraction increases the reproducibility of ADCbased radiomics features. When normalization is applied, a fixed-bin width approach with smaller widths is suggested. Ó 2019 The Author(s). Published by Elsevier B.V. Radiotherapy and Oncology 143 (2020) 88-94 This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Cervical cancer is the fourth most frequent cancer in women, with an estimated 570,000 new cases in 2018, representing 6.6% of all female cancers worldwide. Cervical cancer still represents a significant burden for middle-and low-income countries [1]. Standard treatment for locally advanced (stage IB2-IVA) cervical cancer is concurrent chemoradiation.Computed Tomography (CT) and Magnetic Resonance (MR) are the standard imaging modalities for cervical cancer staging and evaluation of treatment response. Through appropriate choice of pulse sequences MR imaging provides greater soft tissue contrast than CT and enables assessment of physiological parameters and biochemical function. Diffusion-weighted imaging (DWI) in MR enables measurement of water diffusivity via generation of Apparent Diffusion Coefficient (ADC) maps, and ADC is an established biomarker of tumor cell density and related changes posttherapy [2]. DWI is increasing acquired in addition to T2weighted MRI to detect cervical tumor [3], and pre-treatment tumor ADC has been shown to be p...