Basic And Clinical Study Of Image-guided ~125 I Seed Interstitial Brachytherapy In Pancreatic Cancer

Early Therapy Monitoring of ¹²⁵I seed interstitial implant in animal studies of Pancreatic Cancer XenograftObjective: ¹²⁵I seed interstitial implant brachytherapy has some clinical effectiveness for pancreatic cancer. In this study, through the use of combined micro-positron emission tomography （PET）/computed tomography （CT）, we investigated potential the application of ¹²⁵I interstitial implant in a pancreatic cancer xenograft for early evaluation and diagnosis.Methods: The human pancreatic cell line SWl990 was subcutaneously injected into right lower limb partial dorsal area next to the groin of the immunodeficient BABL / c nude mouse. Tumors were cut into small pieces after tumor formation, and the tumor pieces were inoculated in nude mice.The tumor size reached 8-10mm after six weeks. The mice were randomly divided into 3 groups, the control group （n=4）, empty seed implant group（n=4） and ¹²⁵I implant group （n=4）. Before treatment and one week after treatment, ¹⁸F-FDG Micro-PET/CT scan was performed and then maximum standardized uptake values (SUV_max), mean standardized uptake values (SUV_mean), tumor size and necrosis rate were measured. HE staining and TK1 immunohistochemistry examination were carried out in the paraffin-embedded sample.Results: Before treatment the SUV_max and SUV_mean values of three groups were respectively 2.73±2.29 and 0.58±0.37 vs.2.65±1.36 and 0.56±0.41 vs. 3.63±1.65 and 0.85±0.51 which showed no statistical significance. At one week after treatment the SUV_max and SUV_mean values of three groups were respectively 3.53±1.20 and 0.57±0.26 vs. 3.83±2.13 and 0.59±0.24 vs. 0.29±0.23 and 0.016±0.001, which had a significant difference （F=7.62,P=0.01; F=10.34, P=0.005）. The SUV_max and SUV_mean values of ¹²⁵I implant group were significantly lower than the empty seed implant group and the control group while there was no significant difference between the later two groups. And the SUV_max and SUV_mean in ¹²⁵I seed implant group were significantly lower than before treatment, while for the empty seed group and control group there were no significant difference compared with before treatment.Before treatment, tumor necrosis rate of three groups were respectively （9.75±3.10）%, （11.41±5.33）% and （12.46±4.69）%, with no significant difference. Immunohistochemical staining found the TK1 positive staining index of three groups were respectively （64.25±1.71）%, （62.25±2.22）% and （38.25±1.71）% with statistically significant difference （F=233.67, p<0.001）. The TK1 positive staining index of ¹²⁵I implant group was significantly lower than empty seed implant group and control group （P<0.001）. And the SUV_max values have certain positive correlation with TK1 positive staining index （r=0.85,P=0.001）.Conclusions: Our findings suggest that ¹⁸F-FDG Micro-PET/CT may be useful as a noninvasive imaging modality to assess early response to ¹²⁵I seed brachytherapy in a pancreatic cancer. The efficacy evalution of image-guided ¹²⁵I seed interstitial brachytherapy for advanced pancreatic carcinoma in clinical studyObjective: The purpose of this study was to examine the clinical efficacy of image-guided radioactive iodine-125 (¹²⁵I) seed implantation treatment in patients with unresectable pancreatic cancer.Methods: 40 patients with inoperable pancreatic cancer were enrolled in this study. Of the 40 patients involved in this study, 25 were male, 15 were female, and age ranged from 38 to 89 with 69 on average. Treatment Planning System （TPS） was used to reconstruct 3-Dimensional image of pancreatic tumor and to define the quantity and distribution of ¹²⁵I seeds. ¹²⁵I seeds whose activities ranged 0.5～0.9 mCi/seed were implanted into pancreatic tumor under CT guidance, 1cm apart, avoiding puncturing vessels, pancreatic tube and other nearby organs during the procedure. The tumor matched peripheral dose （MPD） was 31.1～130Gy. Median implanted number of seeds was 36 （range 18-68）, CT scan was done immediately after the procedure to check the quality of the seeds.Results: Median diameter of the tumor was 4.9 cm. Follow-up period was 2 to 30 months. Symptoms of refractory pain were significantly resolved post-interventionally （P<0.05）, and Karnofsky score went up dramatically （P<0.05）. Most often patients reported pain relief 2 to 5 days after implantation. Tumor response which was demonstrated on repeated CT film 2 months post treatment revealed completed relief （CR） in 3 cases, partial relief （PR） in 20 cases, no change （NC） in 14 cases and progression （PD） in 3 cases. Overall responding rate （CR+PR） for this group of patients turned out to be 57.5%. Median survival time for all patients was 10.2 months, while for stage II, stage III, and stage IV were 14.7 months, 10.9 months and 7.1 months respectively. The 6- and 12-month cumulative survival rates were 100%, 88%, 62% and 70%, 41%, 0% by stage subgroup. Elevated serum CA19-9 level before ¹²⁵I seeds implantation were detected in 21 cases, which reduced after 1-3 months.Tumor marker levels significantly reduced compared with that before after ¹²⁵I seed implantation 1 month, and there is significant difference （P <0.05）. 4 seeds of radioactive I-125 were found to migrate to liver in 3 patients. There were no serious complications such as upper GI bleeding, pancreatitis, pancreatic fistula formation and radiation colitis detected during follow-up period.Conclusions: This study suggested that CT-guided brachytherapy using ¹²⁵I seeds implantation is safe, effective, less complicated and can produce adequate pain relief for treating unresectable pancreatic cancer. However, this result required further validation to determine its long-term efficacy.