Radiomic texture analysis correlates with PDAC patient outcomes on SM-88.

Abstract

e16776 Background: SM-88 (racemetyrosine) is a dysfunctional tyrosine derivative; previous studies demonstrated a well-tolerated profile with encouraging efficacy. Recent advances in image analysis using Quantitative Textural Analysis (QTA) have uncovered non-invasive biomarkers that correlate with molecular drivers of cancer and prognostic signatures of response in PDAC. Earlier radiomic data from subjects treated with SM-88 showed a positive correlation between circulating tumor cells and tumor texture at baseline. This study extends those findings to focus on radiomic changes associated with SM-88 doses in a Phase II dose escalation trial (NCT03512756). Methods: Retrospective evaluation of 18 subjects with >1 prior therapy, ECOG PS <2, with no restriction on size, number, or locations of mets, and had baseline (BL) and follow up (FUP) contrast enhanced CTs. Subjects received > 1 cycle of SM-88 at either 460mg (n = 8) or 920mg (n = 10) QD oral doses. CTs were analyzed by the QTA platform (TexRad, Essex, UK) for tumor texture. The largest met of each subject was selected using portal venous phase images. A region of interest was posited on the axial slice with the longest tumor diameter and features automatically generated using voxel resampling to correct for scanner variability across subjects and time points. Results were displayed as histogram frequency curves (HFCs) of pixel densities (Hounsfield Units). First order HFC analysis (mean, StDev, MPP, skewness, kurtosis) at spatial scale filters (SSF) ranging from no filter, to fine, to coarse texture (SSF:0, SSF:2, SSF:6, respectively) were reported. Results: Subjects whose largest lesions showed greater changes in tumor texture at FUP vs. BL were more likely to develop tumor progression (StDev in PD (n = 10) vs SD (n = 7) (1 N/A): -0.07 vs -0.25, p = 0.05). Greater tumor textural changes were associated with poor survival at 180 days (Skewness: Chi-Sq. = 4.81, p = 0.03; HR = 4.1 for above median □Skewssf3). There was a negative change in FUP kurtosis vs BL in the 6 subjects who developed new lesions vs the 12 who did not (mean □kurtosis = -0.67 vs +2.63, p = 0.05). Greater change in tumor texture on FUP vs BL scans was seen in the 460mg vs 920mg group (MPPLD = -0.29, MPPHD = -0.04; p = 0.05) suggesting more tumor stability (less change in texture and better outcomes) was associated with the 920mg dose. Conclusions: Tumor lesions in subjects on 920mg of SM-88 were less likely to show a change in tumor texture and were associated with better outcomes. Using radiomic QTA, less tumor texture variability from baseline may be associated with better outcomes in PDAC subjects.