Tumor radiomic heterogeneity: Multiparametric functional imaging to characterize variability and predict response...

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

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.

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

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

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.

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

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.

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).

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.

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