Dynamic changes in tumor blood flow during chemotherapy: Implications in customized treatment for pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal malignancy, and the optimal selection of neoadjuvant chemotherapy (NAC) remains a critical clinical challenge. Tumor blood flow (TBF) is associated with chemotherapeutic response. However, the role of TBF in regimen-specific outcomes remains unclear. Thus, this association was investigated in the present study. A total of 58 patients with PDAC who underwent pancreatectomy after NAC between 2011 and 2023 were retrospectively analyzed. TBF was quantified using contrast-enhanced computed tomography. Patients were stratified into high and low pre-treatment TBF groups, and the associations between TBF, chemotherapy regimen [gemcitabine plus S-1 (GS), gemcitabine plus nab-paclitaxel (GnP) and modified FOLFIRINOX (mFOLFIRINOX)] and therapeutic pathological response were evaluated. Changes in TBF after treatment and intra-tumoral vascular characteristics were also assessed. A total of 35 (60.3%) and 23 (39.7%) patients were categorized into the low and high TBF groups, respectively. The prevalence of a therapeutic pathological response of at least grade II was greater in the high TBF group (P=0.027). A higher pre-treatment TBF was associated with an improved therapeutic pathological response in patients receiving mFOLFIRINOX (P=0.010) but not in those receiving GnP or GS. In patients with low pre-treatment TBF, GnP therapy increased TBF post-treatment (P=0.004), whereas mFOLFIRINOX and GS did not. Furthermore, post-treatment TBF was correlated with the number of intra-tumoral patent vessels (r=0.486; P<0.001). In conclusion, TBF may serve as a predictive biomarker for selecting neoadjuvant chemotherapy regimens for PDAC. High pre-treatment TBF was associated with improved efficacy of mFOLFIRINOX, whereas GnP may be beneficial for tumors with initially low TBF by improving tumor perfusion during therapy.