Tumor radiomic heterogeneity: Multiparametric functional imaging to characterize variability and predict response following cervical cancer radiation therapy

Abstract

Background: Robust approaches to quantify tumor heterogeneity are needed to provide early decision support for precise individualized therapy.

Purpose: To conduct a technical exploration of longitudinal changes in tumor heterogeneity patterns on dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI), diffusion-weighted imaging (DWI) and FDG positron emission tomography / computed tomography (PET/CT), and their association to radiation therapy (RT) response in cervical cancer.

Study type: Prospective observational study with longitudinal MRI and PET/CT pre-RT, early-RT (2 weeks), and mid-RT (5 weeks).

Population: Twenty-one FIGO IB₂ -IVA cervical cancer patients receiving definitive external beam RT and brachytherapy.

Field strength/sequence: 1.5T, precontrast axial T₁ -weighted, axial and sagittal T₂ -weighted, sagittal DWI (multi-b values), sagittal DCE MRI (<10 sec temporal resolution), postcontrast axial T₁ -weighted.

Assessment: Response assessment 1 month after completion of treatment by a board-certified radiation oncologist from manually delineated tumor volume changes.

Statistical tests: Intensity histogram (IH) quantiles (DCE SI_10% and DWI ADC_10% , FDG-PET SUV_max ) and distribution moments (mean, variance, skewness, kurtosis) were extracted. Differences in IH features between timepoints and modalities were evaluated by Skillings-Mack tests with Holm's correction. Area under receiver-operating characteristic curve (AUC) and Mann-Whitney testing was performed to discriminate treatment response using IH features.

Results: Tumor IH means and quantiles varied significantly during RT (SUV_mean : ↓28-47%, SUV_max : ↓30-59%, SI_mean : ↑8-30%, SI_10% : ↑8-19%, ADC_mean : ↑16%, P < 0.02 for each). Among IH heterogeneity features, FDG-PET SUV_CoV (↓16-30%, P = 0.011) and DW-MRI ADC_skewness decreased (P = 0.001). FDG-PET SUV_CoV was higher than DCE-MRI SI_CoV and DW-MRI ADC_CoV at baseline (P < 0.001) and 2 weeks (P = 0.010). FDG-PET SUV_kurtosis was lower than DCE-MRI SI_kurtosis and DW-MRI ADC_kurtosis at baseline (P = 0.001). Some IH features appeared to associate with favorable tumor response, including large early RT changes in DW-MRI ADC_skewness (AUC = 0.86).

Data conclusion: Preliminary findings show tumor heterogeneity was variable between patients, modalities, and timepoints. Radiomic assessment of changing tumor heterogeneity has the potential to personalize treatment and power outcome prediction.

Level of evidence: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1388-1396.

Keywords: DCE; DWI; MRI; PET; radiomics; tumor heterogeneity.