| BachgroundPancreatic cancer is one of the common malignancies of digestive system. The disease is notoriously difficult to diagnose in its early stages. At the time of diagnosis, 80-90% of all patients have regional spread or distant metastasis. The overall 5-year survival reported by National Institutes of Health (NIH) is only 5% by domestic surgery studies for this disease. The prognosis is very poor as the incidence almost equals to the fatality annually. All patients dead with multiple organ failure caused by regional tumor progression or distant metastasis.The routine treatment for pancreatic cancer mainly include surgery, chemotherapy and external beam radiotherapy. Because of the deep location, complicated surrounding structures, biological Characteristics of neurotropism and vascular invasion. The radical resection rate is only 10-15%. The external beam radiotherapy can not reach an effective dose due to the surrounding irradiation sensitive tisue, the usage is limited as ajunvant procedure by low efficacy, poor tolerance and high toxity. For traditional chemotherapy with gemcitabine-the first line drug for pancreatic cancer, the improvements in response rates seen, although significant, were not great and were obtained with no small amount of patients toxicity, objective responses have been 20% or less. A satisfactory response is hardly obtained for most patients with late stages pancreatic cancer, the mean survival for patients with unresectable disease remains 4-6 months, with a 5-year survival rate of less than 5%. As a systematic disease, the basic study shows that simple treatment is difficult to against the tumor growth, even to improve symptom. More effective treatment techniques or therapy mode is needed for late stages pancreatic cancer. Recently, due to the improvement of technology, many minimally invasive ways/interventional treatments and target treatment, for instance iondine-125 implantation, Transcatheter arterial perfusion chemotherapy moleculer target drugs. Iodine-125 implantation for malignant tumor treatment rised recently accompany with the development of image guided equipment. The merit of Iodine-125 implantation include minimally invasion, low toxicity, highly conformal and good efficacy. The initial experience of Iodine-125 implantation for pancreatic cancer showed well perspective. Arterial perfusion chemotherapy obviously enhanced the regional medicine density, supressed the tumor growth, in certain extent, depressed the reccurence and metastasis rate. With the lower toxicity compare to intrevenious chemotherapy, it helps to improvement the quality of life and survival rate. Presently, there is no prospective clinical study of combining used these two interventional method for pancreatic cancer treatment.This study use CT-guided iodine-125 seed/fluorouracil implants implantation combined regional arterial perfusion chemotherapy by gemcitabine for treatment a group of unresectable pancriatic cancer. The local efficacy, long term survival, safty and clinical benefit response was evaluated.PurposeTo evaluate the clinical benefit response, efficacy and safty of CT-guided iodine-125 seed/fluorouracil implants implantation combined regional arterial perfusion chemotherapy by gemcitabine for unresectable late stages pancreatic cancer. The tumor local control, life quality improvement and life span prolonging by this treatment mode were discussed, aim to find a effective way for late stages pancreatic cancer.MethodsFrom Sep 2006 to Sep 2009, a total of 45 patients(36 male and 9 female, aged 60.2±12.9yr,range 37-81yr) with pancreatic cancer were treated by CT-guided 1251 seed/fluorouracil implants implantation combined regional arterial perfusion chemotherapy by gemcitabine. For all patients, the Kamofsky Performance status (KPS)score was >60, liver function degree was >child B (child A 40; child B 5, recovered to child A after treatment), prediction life span was > 3 months. Patients complicated with obstructive jaundice were underwent chole-intestinal anastomosis, stenting or external drainage to decrease the jaundice, thereafter, to be brought into this treatment. The average tumor diameter was 4.0±0.9cm. All patients was diagnosed based on National comprehensive net work(NCCN) pancreatic adenocarcinoma guideline, confirmed by CT-guided percutaneous needle biopsy. According to UICC stages (2002), these patients include 34 in III stage and 11 in IV stage. None of them received chemo-radiatherapy in any patern before this treatment performed. The tumor images were reconstructed in Treatment Plan System using axial CT images, the matched perepheral dose of iodine-125 was 150-200Gy.The implantation of iodine-125 seed and fluorouracil implants was under CT guidance and local anesthesia. The activity of iodine-125 seed we used was 762-894μci. The interval between iodine-125 seeds was 0.5-1.0cm. During the implantation, the pancreatic duct and blood vessels was avoided. regional arterial perfusion chemotherapy by gemcitabine was performed in one week after iodine-125 seed and fluorouracil implants implantation.All patients entered into follow up period after combined treatment. Enhanced CT scan was performed 1, 3 and 6 months after, aimed to evaluate local efficacy. According to RECIST criteria, the local response was divided into four grade, complete response, partial response, stable disease and progression disease. Clinical benefit response(CBR) evaluation included pain intensity, pain-killer consumption, KPS score, and body quatitative change. The efficacy was divided into utility, stable and useless. kaplan-melier survival analysis was used to calculate the accumulative survival rate in 6, 12 and 18 months. These datas were compared with domestic large quantitative clinical study. ResultsFor the total 45 patients, the mean frequency of CT-guided iodine-125 seed/fluorouracil implants implantation and regional arterial perfusion chemotherapy by gemcitabine was 1.27 and 2.67, respectively. The mean dose of iodine-125 seed and fluorouracil implants implanted was 49.3 and 391mg. The mean dose of GEM and DDP was 1.4 g and 40mg, respectively. The average time of these two processes was 157min and 45min. The follow up period was 5-27 months. 43 patients died of multiple organ failure caused by distant metastasis, two patients were still alive until this writing.1. Feasibility evaluationCT-guided iodine-125 seed/fluorouracil implants implantation were succefully performed in all patients. A total of 55 times CT-guided implatation were performed in order to equalize the dose of iodine-125 seed and fluorouracil. During the operation, portal vein/superior mesenteric vein(SMV)/splenic vein injured was found in 4 cases, pancreatic duct injured was found in 1 case and doubtful intestinal injured was found in 2 cases. No major complications(hemorrahge, pancreatic fistula and infection) occurred intraoperative.2. Local efficacy evaluationAfter 6 months, the follow up CT images showed 9 cases with complete local response, 23 cases with partial local response, 11 cases with stable disease and 2 cases with progression disease. These two patients underwent supplementary implantation 2 months after. The local effective rate(CR+PR) and local contral rate(CR+PR+SD) was 71.1% and 95.6%, respectively.3. Clinical benefit response evaluationThe CBR in total patients was 73.3%. The average time of starting allievation of pain was 5.4 day(range 1-9d). The median duration of CBR was 7.5 month. The mean value of CA19-9 in pretretment and posttreatment was 1047.81±2012.17U/ml and 621.82±907.58U/ml. There are significant differences. The CA19-9 value had 50% decrease in 80% of patients and turned to negative in 24.4% of patient, maintained >4 weeks.4.Life spanThe meso-life span(MS) and mean progression free span(PFS) was 14.7 month(range 5- 27 month) and 6.5 month(range 1-11 month). The accumulative survival rate in 6, 12, 18 months was 97.8%, 84.4% and 26.7%, respectively. Two patients were still alive with tumor until this writing.5. Safty evaluationAccording to the tumor toxicity grading by RTOG and NCI-CTC, two patients(4.4%) had toxicity grading achieved grade 2. No major complications occurred, including pancreatic fistula, radiation enterocolitis, digestive tract perforation, acute pancreatitis, hemorrhage and infection. About half patients has low-grade fever and a transient rise of neutrophilic granulocyte 24-48h after combined treatment. There are no significant difference in peripheral white blood cells counting, T-cell subgroups and activity of NK cells in pretreatment and posttreatment. Iodine-125 seed migrating to liver was found in 4 cases. No impact fo liver function was found.6. Prognosis risk factorsThe local response, 5-FU dose, clinical stage and GEM-TAI treatment were Prognosis risk factors.ConclusionCT-guided iodine-125 seed/fluorouracil implants implantation combined regional arterial perfusion chemotherapy by gemcitabine for pancreatic cancer was safe and minimally invasion in operative procedure with low toxicity rate and repeatable performance. The local efficacy, reccurence control and status improvement lead to elivation of quality of life and prolonging life span compared with domestic large quantitative clinical study.Summary A prospective study of CT-guided iodine-125 seed/fluorouracil implants implantation combined regional arterial perfusion chemotherapy by gemcitabine for late stages pancreatic cancer. CT-guided iodine-125 seed/fluorouracil implants implantation was adopted for local contral and regional arterial perfusion chemotherapy by gemcitabine for regional treatment. We intend to use the superiority of both techniques to explore a minimally invasive treatment mode to benefit for patients with unresectable pancreatic cancer. Our study shows this mode can provide satisfactory local efficacy and long term efficacy. Meanwhile, we found that by full preparation, carefully operation and skillful technique, CT-guided guided iodine-125 seed implantation for pancreatic cancer is feasible, safe and with low dangerous. As minimally invasive treatment becomes the tendence in future, CT-guided precise implantation will replace the complicated and more injured intraoprative implatation. This study provides an effective non-surgery way for late stages pancreatic cancer. Due to the limited cases and lack of randomized controlled study, the efficacy of this treatment needs further investigation. |
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