PO-438 Hyperthermia as neoadjuvant treatment for pancreatic tumours in murine models

IntroductionPancreatic ductal adenocarcinoma (PDAC) is the most common form of pancreatic cancer. The hallmarks of this malignancy, such as it’s deprived vasculature, dense tumour stroma and hypoxic tumour microenvironment are some of the reasons for very poor chemotherapy and radiotherapy treatment efficacy. In these regards, a new combinatory treatment regimen was proposed:1 non-invasive radiofrequency (RF) hyperthermia treatment to increase tumour perfusion, enhance cancer cell death and immune system stimulus;2 chemotherapy regiment with Gemzar and Abraxane.Material and methodsOrthotropic and subcutaneous models of PDAC were induce by injection of PANC-1, AsPc-1 and Pan_O2 cancer cells into Balb/c nude or C57BL/6J mice. Tumour growth was monitored via ultrasound VEVO2100. Tumour perfusion after hyperthermia was monitored via intravital confocal microscopy and ultrasound microbubble contrast imaging. The tumour active vasculature was investigated using Doppler imaging. The chemotherapy with Gemzar and Abraxane was administered in combination with RF hyperthermia. A portable-RF system was used to produce local hyperthermia in the tumour tissue. The device is powered by 200 W and emits 13.56 MHz electric fields. The entire treatment scheme was repeated a total of 6 times at 72 hour time intervals (Q3D × 6 protocol) resulting in 16 days of treatment. The variety of histochemistry staining was performed post mortem to show the influence of treatment on the tumour vasculature and the degree of perfusion and necrosis.Results and discussionsWe showed that RF hyperthermia treatment as a neoadjuvant therapy can be promising for PDAC treatment. However, the effect is still unpredictable and depends on pre-existing tumour physiology before therapy. We established the most effective RF hyperthermia procedure to increase drug perfusion into tumour tissue (41°C for 20–30 min). We studied a variety of chemotherapy dosages to adjust clinical protocols into mouse model. The Doppler ultrasound imaging was found to be a useful tool to investigate vasculature response to treatment.ConclusionThe benefit on Gemzar and Abraxane treatment was confirmed in mice. Although, the effect of treatment was statistically insignificant in comparison to saline treated mice in long-time scale (one year). The benefit of RF hyperthermia was hardly visible in the short-term and completely insignificant during long-term observation. However, increased perfusion in the tumour microenvironment