Continuous Low-dose-rate Irradiation of Iodine-125 Seeds Inhibiting Perineural Invasion in Pancreatic Cancer

BACKGROUND: Perineural invasion (PNI) is a histopathological characteristic of pancreatic cancer (PanCa). The aim of this study was to observe the treatment effect of continuous low-dose-rate (CLDR) irradiation to PNI and assess the PNI-related pain relief caused by iodine-125 ((125)I) seed implantation. METHODS: The in vitro PNI model established by co-culture with dorsal root ganglion (DRG) and cancer cells was interfered under 2 and 4 Gy of (125)I seeds CLDR irradiation. The orthotopic models of PNI were established, and (125)I seeds were implanted in tumor. The PNI-related molecules were analyzed. In 30 patients with panCa, the pain relief was assessed using a visual analog scale (VAS). Pain intensity was measured before and 1 week, 2 weeks, and 1, 3, and 6 months after (125)I seed implantation. RESULTS: The co-culture of DRG and PanCa cells could promote the growth of PanCa cells and DRG neurites. In co-culture groups, the increased number of DRG neurites and pancreatic cells in radiation group was significantly less. In orthotopic models, the PNI-positive rate in radiation and control group was 3/11 and 7/11; meanwhile, the degrees of PNI between radiation and control groups was significant difference (P < 0.05). At week 2, the mean VAS pain score in patients decreased by 50% and significantly improved than the score at baseline (P < 0.05). The pain scores were lower in all patients, and the pain-relieving effect was retained about 3 months. CONCLUSIONS: The CLDR irradiation could inhibit PNI of PanCa with the value of further study. The CLDR irradiation could do great favor in preventing local recurrence and alleviating pain.