Use of time-density curves of dynamic contrast-enhanced computed tomography for determination of the histological therapeutic effects of neoadjuvant chemotherapy for pancreatic ductal adenocarcinoma

The present study aimed to investigate the histological changes caused by neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC), and to demonstrate the use of time-density curves (TDCs) of dynamic contrast-enhanced computed tomography (CECT) for determination of the histological therapeutic effects of NAC for PDAC. A total of 96 patients with PDAC were examined; 46 underwent NAC (NAC group) and 50 did not undergo NAC (non-NAC group). Based on histological therapeutic effect and using the area of residual tumor (ART) grading system, the NAC group was divided into low-responders and high-responders. Histological analysis was used to evaluate the densities of cancer cells, cancer-associated fibroblasts (CAFs), microvessels and stromal collagen fibers in the NAC and non-NAC groups. Radiological analysis was used to evaluate the TDCs of three slopes of the NAC group, namely slopes between the non-contrast and arterial phases (delta 1 and delta 1 '), between the arterial and portal phases (delta 2 and delta 2 '), and between the portal and equilibrium phases (delta 3 and delta 3 '). delta 1-delta 3 were before NAC, whereas delta 1 '-delta 3 ' were after NAC. Changes in delta 1, delta 2 and delta 3 before and after NAC were denoted as delta delta 1 (=delta 1 '-delta 1), delta delta 2 (=delta 2 '-delta 2) and delta delta 3 (=delta 3 '-delta 3). ART grading system, histological examination and radiological examination data were also statistically analyzed. Histological examination revealed a significant decrease in cancer cells and CAFs, and a significant increase in stromal collagen fibers due to NAC (P<0.01). Radiological examination revealed that delta 1 ' was significantly higher than delta 1 in low-responders (P<0.05), whereas delta 2 ' was significantly lower than delta 2 in high-responders (P<0.01). delta delta 2 was significantly lower and delta delta 3 was significantly higher in high-responders than in low-responders (P<0.01 and P<0.05, respectively). Receiver operating characteristic curve showed that delta delta 2 and delta delta 3 were effective indicators of the histological therapeutic effect of NAC. In conclusion, the TDC of dynamic CECT may be useful for determining the histological therapeutic effect of NAC for PDAC.