Analyzing the effect of neoadjuvant stereotactic ablative body radiotherapy on pancreatic tumor perfusion using...

The objective of this study was to investigate the feasibility of administering neoadjuvant stereotactic ablative body radiotherapy (SABR) for the purpose of increasing pancreatic tumor perfusion, hence potentially improving systemic drug delivery in patients with resectable (RPC) or borderline-resectable pancreatic cancer (BRPC).

Neoadjuvant SABR was administered to RPC (n=1) and BRPC (n=5) patients with a dose prescription of 27-30 Gy in 3 fractions and a dose boost up to 45 Gy to the metabolically active areas of the tumor. Computed tomography perfusion (CTP) studies were acquired at baseline, 6 hours after delivering the first SABR fraction (post-1^st-fx), and 3-4 weeks after completing SABR (post-RT). For BRPC patients, studies were also acquired after neoadjuvant chemotherapy (post-cx), which preceded SABR. Using a deconvolution-based CTP software, the tumor blood flow (BF), blood volume (BV), permeability-surface area product (PS), and extravascular extracellular volume (V_e) were calculated at each study instance. Additionally, a surrogate measure of the tumor cell density (CD) was derived from V_e.

The post-1^st-fx tumor BF was significantly higher than baseline (p=0.010) for the RPC patient and 2 other BRPC patients who had acquired a pre-treatment baseline scan. The post-RT BF, PS, V_e were also significantly higher than baseline (p<0.05), and a decrease in CD could be observed after the initial treatment (% decrease relative to baseline: post-cx for BRPC = 23%; post-RT for RPC = 14%). The BRPC patients showed a subsequent decrease in CD at post-RT relative to post-cx (<5%). For all BRPC patients, the post-1^st-fx BF was significantly higher relative to post-cx (p=0.033), followed by a non-significant decline at post-RT. Conversely, the PS showed a significant decrease at post-1^st-fx relative to post-cx (p<0.001), although the post-RT changes showed no consistent trend. The V_e was still significantly higher at post-RT relative to post-cx (p=0.015).

This study provides preliminary evidence that delivering SABR in the neoadjuvant setting for RPC and BRPC patients can induce acute and sustained increases in pancreatic tumor perfusion. Additionally, this study shows that tumor CD may have adequate sensitivity as a biomarker for monitoring patient response to standard-of-care therapy.