Endoscopic Ultrasongraphy-guided Interstitial Implantation Of Iodine125 Seeds Combined With Chemotherapy In The Treatment Of Unresectable Pancreatic Carcinoma: A Prospective Random Control Study

BackgroundPancreatic carcinoma is difficult to detect in early stage for its anatomic properties. Most cases are in advanced stages and lost the opportunity of exairesis when they are defined diagnosed.The prognosis of patients with pancreatic cancer is extremely poor, with overall 5-year survival rate of approximately 5%.In west,the incidence of pancreatic cancer is 3%,pancreatic cancer has become the fifth cause of death.Nearly one half of the patients have metastasis when the diagnosis was defined,with the median duration of less than 6 month.About one-third cases are locally advanced cancer with the median range of 6 to 9 month.Only less than 15%cancers could be resected by surgery.Therefore, exploring the novel conservative method of treating pancreatic carcinoma is worth momentous clinical significance.At present,the main therapy for most cases of locally advanced cancers involves kinds of radiotherapy in vivo and in vitro,and the chemotherapy(Gemcitabine is widely used).Chemotherapy could relieve the symptoms, promote the quality of life and improve the survival.Since 1997,chemotherapy with the drug gemcitabine showed better curative effect than 5-Fu and has been a standard treatment option for patients with advanced pancreatic cancer that cannot be removed by surgery.It was reported that chemotherapy of gemcitabine with radiotherapy could significantly improve the median duration of the patients.However,the radiation damage of external radiation to the surrounding tissues of pancreas was hard to control,which limited its application.Objectives With the development of endoscopic ultrasonography(EUS),remedial EUS has become more and more important and make EUS-guided implantation of radioactive particle possible.Since EUS guided punctuation possesses many advantages, such as accurate localization,less trauma,short punctuation distance,and the safety has been confirmed in previous animal trials,we select EUS-guided Iodine-125 seed implantation combined with chemotherapy of gemcitabine,comparing simple chemotherapy of gemcitabine,and assessed the curative effect and safety in treating the unresectable pancreatic carcinoma in order to approach the feasibility and clinical worth of EUS-guided Iodine- 125 seed implantation.Methods:Forty-one patients with unresectable pancreatic carcinoma were randomly divided into two groups,one group(Group A) included 21 cases which were accepted EUS-guided Iodine-125 seed implantation combined with chemotherapy of gemcitabine, the rest 20 cases(Group B) were treated with chemotherapy of gemcitabine.All patients were involved in follow up after the first therapy.The principal indexes of assessing the curative effect included clinical benefit response(CBR),objective tumor response,safety and the evaluation of quality of life.The changes of tumor markers,progression-free survival(PFS),median duration and 5-year survival rate were secondary indexes.ResultsThe general conditions of the patients of both two groups were comparable.For Group A,the times implanted ranged from 1 to 6 times,with a median implant times of 1.8 times.The total implanted volume of Group A is 6g.For Group B,the times implanted ranged from 1 to 6 times,with a median implant times of 2.4 times.The total implanted volume of Group B is 8g.A median of 26 seeds(range,10-50) was implanted per patient, with an average activity per seed of 17.2 mCi(7.0-35.4mci) and a median implanted times of 1.7 times(range,1-4 times).The median follow-up of Group A and Group B was 5.5 months(range:2-16 months) and 5.2 months(range:2-14 months),respectively.1.Curative effects(1) Clinical benefit response(CBR):CBR of Group A and Group B were 57.10% and 25%respectively,and there were significant difference between two groups(P=0.04). Patients of Group A experienced relief an average of 4d(n=12),while the patients of Group B experienced relief an average of 4w(n=5).The median CBR was 21w and 15w for Group A and B,respectively.(2) For Group A,0 cases of completely response,4 cases of partial response,9 cases of stable disease,8 cases of progressive disease,The objective tumor response rate were 61.9%and 25%for Group A and B.The objective tumor response of Group A was obviously better than Group B(P=0.028).(3) Progression-free survival(PFS):Median PFS of Group A was 4m(95% CI,2.51±5.49),while median PFS of Group B was 3m(95%CI,1.89±4.11).There were no significant difference between two groups(P=0.160).But the PFS of the patients with positive CBR was longer than the PFS of those with negative CBR(P＜0.05).(4) Overall survival(OS):The median OS of Group A was 11m(95%CI, 1.835±20.17),including 7 cases died(33.71%),the maximum OS was 16m,the OS of 5 cases(23.60%) have exceed 8m so far.The median OS of Group B was 6m(95% CI,3.39±8.61),including 10 cases died(33.71%),the maximum OS was 14m,the OS of 3 cases(15.00%) have exceed 8m so far.The OS of two groups were no significant difference(P=0.65).(5) CA19-9:The value of CA19-9 of 4 patients of Group A decreased over 50%, while the value of CA19-9 of merely 1 patient of Group A decreased over 50%.2.Safety assessmentThe number of toxic and adverse effects that occurred in the 41 study patients, classified according to the the National Cancer Institute Common Toxicity Criteria (NCI-CTC) and the criteria of Radiation Therapy Oncology Group(RTOG).The toxicity was analyzed by CMH method,and there was no significant difference between two groups.Toxicity exceeded Grade 2 was about 4.8%.All involved patients with iodine-125 seed implantation did not complicated with pancreatic fistula,radiation enterocolitis, perforation of alimentary tract,acute pancreatitis and infection,etc.Fifty percent of patients of Group A appeared low-grade fever with increasing of neutrophil,5 cases(24%, 5/21) had the shifting and loss of the iodine-125 seed.The iodine- 125 seed immigrated to liver and enteric cavity,but without abnormal hepatic function and the diarrhea.Conclusions EUS-gnided Iodine-125 seed implantation was a novel technique for treating the locally advanced stage of pancreatic carcinoma,with obviously more advantages on CBR and RR.The patients of Group A showed great improvement of pain relieving,KPS physical score and body weight.The CBR of Group A was 57.11%,while the CBR of Group B was 25%(P=0.04).The objective tumor response rate were 61.90% and 25%for Group A and B(P=0.03).The median duration and Median PMS of Group A were 11m and 4m respectively,while those of Group B were 6m and 3m.Above results suggested that EUS-guided iodine-125 implantation combined with chemotherapy of gemcitabine showed better effects.