Changes in Apparent Diffusion Coefficient of the Dominant Tumor During Dose-Painted Radiation Therapy and High Dose Rate Brachytherapy for Prostate Cancer

Abstract

Dose escalation has successfully improved cancer outcomes for patients with localized prostate cancer. Targeting subprostatic regions of tumor burden for dose-intensification may further improve tumor control and reduce dose to surrounding normal tissues. Quantitative MRI may provide a clinically useful evaluation of early radiation response to enable the adaptation of dose. Our objective is to determine whether the ADC derived from diffusion-weighted imaging (DWI) of prostate tumors may be used as a biomarker for evaluation of early radiation response and dose adaptation. Patients with biopsy proven prostate adenocarcinoma visualized on MRI prior to radiotherapy were recruited to participate in a prospective trial in which patients received 76 Gy in 38 fractions to the prostate and either an integrated boost (IB) (19 Gy/38#) or an HDR boost (10 Gy/1#) to the dominant tumor. Patients underwent endorectal coil multiparametric MRI (3T Verio, Siemens) at baseline and during week 6 of treatment. ADC was calculated from in-line processing of DWI (b values of 0, 100, 600, and 1000 s/mm2). Dominant tumors, prostate, and common reference points were defined on the baseline T2 weighted (T2w) image (Pinnacle). The prostate and common reference points were again defined on the week 6 T2w image. Deformable registration (Morpheus) was applied to the baseline prostate and reference contours to guide segmentation of the tumor volumes (no longer clearly visible) in the week 6 ADC maps. Volume of interest (VOI) voxel based histogram analysis of mean, skewness, and kurtosis were used to assess ADC response. Of 80 enrolled patients, the first 17 were analyzed. 8 patients received IB and 9 patients received HDR. Tumor volumes were small (baseline mean 2.0 cm3, 95% CI 1.6-2.9 cm3). For all 17 patients, there was a statistically significant increase in tumor ADC from baseline (mean 1.12x10-3 mm2/s, 95% CI 1.04-1.19 x10-3 mm2/s) to week 6 of treatment (mean 1.34x10-3 mm2/s, 95% CI 1.29-1.39 x10-3 mm2/s, p<0.001). Tumor ADC kurtosis increased significantly from 3.1 to 4.0 (95% CI 2.7-3.6 at baseline, 3.3-4.8 at week 6, p=0.04). Mean tumor ADC increased by 24.5% (95% CI 10-39%) in the IB-VMAT arm and 20% (95% CI 6-34%) in the VMAT+HDR arm (p=0.6). Our preliminary data confirm a statistically significant increase in tumor ADC during radiotherapy, worthy of further investigation. Complete analysis of the study cohort will elucidate relationships between early changes in tumor ADC and subsequent response to treatment.