Journal of Cancer Research and Therapeutics

REVIEW ARTICLE
Year
: 2018  |  Volume : 14  |  Issue : 7  |  Page : 1455--1462

Chinese expert consensus on radioactive 125I seeds interstitial implantation brachytherapy for pancreatic cancer


Baodong Gai1, Fujun Zhang2,  
1 Department of General Surgical, Third Hospital of Jilin University, Changchun, China
2 Department of Medical Imaging, Minimally Invasive Interventional Center, Sun Yat-Sen University Cancer Center, Guangzhou, China

Correspondence Address:
Baodong Gai
Department of General Surgical, Third Hospital of Jilin University, 126 Xiantai St, Changchun 130031
China
Fujun Zhang
Department of Medical Imaging, Minimally Invasive Interventional Center, Sun Yat-Sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060
China

Abstract

Pancreatic cancer, also known as exocrine pancreatic carcinoma or pancreatic ductal adenocarcinoma, is one of the most challenging tumor entities worldwide, which is characterized as a highly aggressive disease with dismal overall prognosis. Treatment options for patients with locally advanced pancreatic cancer include surgery, chemotherapy, and radiotherapy. In many cases, surgical resection is not possible due to the advanced stage at diagnosis and poor responses to current treatments, therefore, treatment alternatives have to be performed. However, brachytherapy through radioactive 125I seeds (RIS) implantation into pancreatic cancer has been first applied in unresectable carcinoma and made accuracy curative effects. Therapeutic procedures of RIS implantation for pancreatic carcinoma were not identical in domestic medical centers, making it hard to achieve homogeneity and affecting the efficacy seriously at last. To maximize the benefits of RIS for patients with pancreatic cancer, Chinese Medical Doctor Association of Radioactive Seed Implantation Technology Expert Committee and Committee of Minimally Invasive Therapy in Oncology, Chinese Anti-Cancer Association, Radioactive Seed Therapy Branch organized and helped establish China expert consensus on RIS implantation for the treatment of pancreatic cancer, to provide a reference for clinical practices.



How to cite this article:
Gai B, Zhang F. Chinese expert consensus on radioactive 125I seeds interstitial implantation brachytherapy for pancreatic cancer.J Can Res Ther 2018;14:1455-1462


How to cite this URL:
Gai B, Zhang F. Chinese expert consensus on radioactive 125I seeds interstitial implantation brachytherapy for pancreatic cancer. J Can Res Ther [serial online] 2018 [cited 2019 Mar 19 ];14:1455-1462
Available from: http://www.cancerjournal.net/text.asp?2018/14/7/1455/247735


Full Text



 Introduction



In China, the incidence of pancreatic cancer was high with the steady uptrend, particularly in the population older than 65 years old, whose incidence of pancreatic cancer has increased as fast as that the worldwide recently. Among them, the crude incidence rate of pancreatic carcinoma arose at a rate of 1.86% and 2.1% per year in male and female, respectively, between 1998 and 2007. In the first time for the cause of death review sampling during 1970s, mortality of pancreatic cancer in China was relatively low. However, in the second time for the cause of death review sampling in 1990s, pancreatic carcinoma was ranked as the 10th highest cause of cancer death in China. Moreover, the third time for cause of death review sampling suggested that pancreatic cancer ranked as the 7th highest cause of cancer death in China.[1],[2],[3],[4] In the United States, 45,520 people were diagnosed and 38,460 people died from pancreatic cancer, contributing to the fourth cause of cancer death.[5] These results were in accordance with the data estimated from the European Union in 2002.[6]

Pancreatic cancer is a high-grade digestive malignant tumor with 1-year overall survival (OS) rate of <25%. Among which, the patients receiving surgical excision presented a 5-year OS rate of no more than 5%. Moreover, the median OS (mOS) of patients with locally advanced pancreatic cancer and metastatic focus was 6–10 months and 3–6 months, respectively. There was nearly neither opportunity to receive surgery for patients with pancreatic cancer of stage III-IV, nor surviving more than 5 years. Professional committee on pancreatic cancer of Chinese anticancer association enrolled 2340 cases of pancreatic cancer in 14 tertiary hospitals covering eight provinces and two cities during 1990–2000. Moreover, the clinical epidemiology statistics estimated that mOS of 17.1 months could be achieved in 20.9% with radical operation, and mOS of 9.0 months could be obtained in 45.8% with palliative operation. These data also suggested that the 10.3% of patients who went through exploratory surgery owned mOS of 4.5 months, while 23.0% of patients received other treatments (except for operation) owned mOS of 3.0 months.[7] Clinical data of 2061 patients with adenocarcinoma of the pancreas during 2000–2011 were analyzed. Results showed that 1657 of 2061 patients who underwent radical resection presented a median survival of 19.6 months. However, for 271 patients receiving palliative resection, the median survival was 7.2 months.[8] However, although operation modes have made continuous progression in the past two decades, there was no notable improvement in median survival as well as 5-year survival after surgery. About 81.6% of patients with pancreatic cancer were diagnosed as advanced tumors, it was difficult to get rid of the tumor completely through radical resection, because the pathogenesis of pancreatic cancer is concealed with active biological behavior, high degree of malignancy, high risk of local treatment, more complications as well as increased age-specific incidence, causing difficulties to clinical treatment.[8],[9] However, brachytherapy via radioactive 125I seeds (RIS) implantation for treating pancreatic cancer was first applied in unresectable carcinoma of the pancreas and showed accuracy curative effects.[10] Thus, plenty of clinical and fundamental research performed by researchers internally sprung up and made remarkable achievements, including implantation methods, guided ways, calculating dose, and indications for operation.[11] Therapeutic procedures were not identical for domestic medical centers to apply RIS treatment to pancreatic carcinoma, making it difficult to obtain homogeneity and seriously affecting the efficacy at last. To maximize the benefits of RIS for treating patients with pancreatic cancer, Chinese Medical Doctor Association of Radioactive Seed Implantation Technology Expert Committee and Committee of Minimally Invasive Therapy in Oncology, Chinese Anti-Cancer Association, Radioactive Seed Therapy Branch organized and helped to establish Chinese expert consensus on RIS implantation for the treatment of pancreatic cancer, to provide a reference for clinical practice. Given the rapid development of related research both at home and abroad, it is inevitable that there will be omissions in this consensus. We hope relevant professionals can propose valuable suggestions and provide a beneficial basis for the future revision.

Access and related requirements

RIS implantation in brachytherapy technology implementation has relevant requirements including practitioners, venues, wards, hospitals, quality control, and radiation protection.

RIS implantation practitioners, venues, and medical institutions related to the interpretation of indicators.[12],[13],[14]

RIS implantation therapy technique and clinical application quality control index reference.[12],[15]

RIS ward radiation protection management standards reference.[16]

Indications and contraindications

For the RIS implantation for treating pancreatic cancer, indications: (1) Patients with estimated survival of more than 3 months cannot undergo operation. (2) Metastases of pancreatic cancer and local lymph node metastasis. (3) Patients who are unwilling to and (or) cannot accept radical surgery due to other concomitant diseases. (4) Pancreatic tumor resection residual disease and/or tumor bed position. (5) Patients with estimated survival of <3 months can select carefully this therapy to relieve persistent upper abdominal pain and back pain.[17],[18] Patients with primary tumor (maximum diameter >6 cm) should carefully select this treatment.[19] Contraindications: (1) there is powerful evidence that the tumor has been widely transferred, (2) patients who suffer severe tendency of hemorrhage and the tumor concomitant with acute pancreatitis, peritonitis, massive ascites, and (3) patients cannot afford RIS implantation surgery due to dyscrasia.

RIS implantation is much widely applied for pancreatic cancer in China than that of other countries. RIS implantation into carcinoma can be applied for treating all stages of pancreatic cancer [20] and contributes to favorable curative effects, even superior to radical surgery. However, patients should receive surgery if the tumor can be removed according to preoperative assessment recommended by the experts.

Some domestic scholars suggest that RIS can be implanted in sublesion area of pancreatic cancer and the regional of lymphatic drainage pathways, at the same time, they also advocate to implant RIS into hematoma as well as tissues adjacent to tumor of pancreatic cancer, and lymphatic drainage route in the stomach-intestine, gallbladder-intestinal bypass surgery.[21] Furthermore, there is currently no evidence that the survival and life quality of patients can be improved with prophylactic use of RIS into the lymph node. Moreover, complicated lymphatic drainage and metastasis of pancreatic cancer lead to operation blindness for implanting RIS in the lymphatic drainage pathway; hence, preventive RIS implantation is not recommended by experts. The above conclusion stems from the extent of lymph node dissection changes in the surgery of radical resection of pancreatic cancer over the past 30 years, from the stage of expansion of lymph node dissection to the stage of expansion of dissection verification stage. Then, consensus for the extent of lymph nodes dissection has been eventually achieved.[22],[23],[24] Due to the current high rate of imaging diagnosis,[25] the experts suggest that patients can receive one-stage RIS implantation therapy considering the diagnosis of local lymph node metastasis and local metastases according to imaging.

Preoperative affirming pancreatic tumor with pathological diagnosis

Pancreatic adenocarcinoma NCCN Guidelines Version 1. 2017 recommended that endoscopic ultrasonography should be performed in patients with pancreatic cancer, on condition that imaging assessment showed that they could undergo surgery to identify the initial site of tumor invasion. Besides, if clinically indicated, endoscopic ultrasonography aspiration biopsy is also required to clarify the pathological diagnosis, for confirming the diagnosis of metastatic lesions. However, NCCN also repeatedly emphasized that there was no necessity to obtain pathological diagnosis before surgery for resectable or borderline resectable lesions.[26]

RIS implantation is an irreversible surgical procedure because it is difficult to remove the RIS after their implantation, and there is no way to make the activity of the RIS rapidly and artificially fall. Therefore, it is very important to clarify the pathological diagnosis of pancreatic masses before surgery for avoiding unnecessary misdiagnosis and mistreatment. At the same time, the exact pathological diagnosis can offer evidence for the follow-up of adjuvant therapy, especially for the chemotherapy. The experts hold the view that pathological diagnosis of pancreatic masses should be confirmed before performing the RIS implantation.

Endoscopic ultrasound-guided fine-needle aspiration biopsy has been proposed as an approach to obtain pancreatic tumor tissue specimens. Compared with ultrasound or computed tomography (CT)-guided percutaneous biopsy, endoscopic ultrasound-guided fine-needle aspiration biopsy shows shorter path than other percutaneous punctures, penetrating the paries posterior gastricus and the duodenal wall to directly reach the tumor site, giving rise to the lower proportion of metastasis through needle tract and higher safety.[27],[28],[29] Based on that, ultrasound or CT-guided percutaneous biopsy is frequently recommended for metastatic lesions. However, ultrasound- or CT-guided percutaneous pancreatic tumor biopsy is recommended for hospitals without approach to perform endoscopic ultrasound-guided fine-needle aspiration biopsy.

Selection of radioactive 125I seeds implantation and imaging guide methods

So far, the modalities applied for RIS implantation mainly include ultrasound-guided intraoperative RIS implantation, percutaneous puncture under the image guidance, and ultrasound-guided endoscopic RIS implantation. The selection of implantation modalities depends on many factors: The location of the patient's pancreatic tumor and their relationships with adjacent organs, the extent of vasculature, operator's experience with different guidance modalities, as well as equipment and so on. For patients with pancreatic cancer who can receive resectable or borderline resectable operation based on preoperative evaluation, ultrasonic-guided RIS implantation is now the modality of choice, especially when it is indeed difficult to perform tumor resection or incomplete resection during intraoperative exploration. Besides, the selected ultrasound probe should be as small as possible; otherwise, it would affect the accuracy of RIS implantation. For patients who need to receive stomach-intestinal, biliary-intestinal bypass surgery, RIS implantation can also be selected in the surgery.[30] Furthermore, imaging-guided percutaneous puncture or endoscopic ultrasonography-guided RIS implantation should be accepted for pancreatic cancer patients without resectability.[31]

Since there are different imaging modalities of guidance as well as the existing equipment in the hospital, the choice of imaging guidance to implant RIS mainly depends on operator's experience. Nowadays, the modalities applied for imaging guidance of RIS implantation mainly included ultrasonography, CT, and magnetic resonance imaging, with varied advantages and disadvantages.[32],[33]

Experts recommend that operators should select their familiar modalities of imaging guidance RIS implantation based on the specific circumstances of the tumor.

With the development of RIS implantation technology, three-dimensional (3D) printing template assisted CT-guided percutaneous biopsy makes the RIS implantation more accurate and can comply with the preoperative TPS program better, effectively shortening the operation time.[34],[35] For the fixed, superficial tumors, the utilization of 3D-printing template-assisted puncture can obtain successful operation.[36] However, plenty of problems remain to be solved in the 3D-printing template-assisted RIS implantation:[37],[38],[39] (1) The template is difficult to reset. (2) The locomotive organ is not easy to operate. (3) The tumor itself can grow bigger or become smaller caused by other adjuvant therapy during the long template preparation process; thus, it is necessary to change the treatment plan earlier; nevertheless, the template did not allow the treatment plan to be changed. (4) For the deeper tumor, it is easy to produce offset of needle tract due to the relatively far puncture path, followed by greater possibility of side injury. (5) It needs a higher cost.

Pancreatic cancer is located at a deep and special anatomical position. Besides, its surrounding tissues and organs show a great activity of breathing and heartbeat, which are rapidly growing. Furthermore, there is complicated vasculature (blood vessels, lymphatic vessels, bile ducts, and pancreatic ducts) around the tumor. These above-mentioned factors limit the application of the template. Therefore, CT-guided 3D printing template-assisted RIS implantation in pancreatic cancer has certain limitations, which should be performed with caution.[40]

Therapeutic doses

Radiation therapy presents an increasing trend in the application of locally advanced pancreatic cancer (including adjuvant therapy); however, there is no clear consensus in the maximum appropriate dose of radiation therapy yet. NCCN Pancreatic Cancer Version V2. 2017 considers gemcitabine or 5-FU-based radiotherapy to be an alternative regimen for the adjunctive therapy. Adjuvant radiotherapy dose of 45–54 Gy is recommended to apply after surgical resection, while radiation dose of 50–60 Gy from the 2015 version has been reduced to the 45–54 Gy currently, for patients with unresectable tumors.[41] The standard dose of conventional external radiotherapy for pancreatic cancer in China is 60 Gy for 10 weeks,[42] which is close to the maximum tolerated a dose of normal tissues. However, it is much lower than that of radiation therapy for tumor remission in pancreatic cancer.

No definite optimal therapeutic dosage has been recommended using interstitial implantation of RIS for the therapy of pancreatic cancer so far. The clinically recommended tumor matched peripheral dose (MPD) is 80–145 Gy and the curative MPD is 145 Gy.[43],[44],[45] Peretz et al.[10] reported that the minimum peripheral dose was 136.6 Gy, which exceeded the recommended dosage of external radiotherapy in the NCCN guidelines, thus potentiating curative efficacy of pancreatic cancer.

Preoperative preparation

General status preparation

Considering that patients with pancreatic adenocarcinoma present a higher proportion of obstructive jaundice, it is necessary to perform percutaneous transhepatic biliary drainage before surgery. For patients with jaundice for a long time as well as poor liver function, it should be synergistic with drug liver protection.[47] Therefore, liver function can be restored within a short time, enabling to perform both anesthesia and surgery in those patients. Patients with obstructive jaundice often exist Vitamin K3 deficiency, resulting in the lack of clotting factors and tendency to bleeding during surgery. As a result, preoperative supplement should be provided. Other preoperative preparations are the same as general preoperative routine preparation.[46]

Intestinal anti-inflammatory drugs are supposed to be applied before nonopen surgery. Besides, keeping the patients off the food and water, gastrointestinal decompression, the application of inhibition of gastric acid drugs, and inhibition of pancreatic enzyme secretion drugs are also necessary 24 h before the operation. In addition, patients should receive not only bowel line cleaned 6–12 h before the operation but also intravenous antibiotics 30 min before surgery.

Preoperative treatment plan

The tumor will be evaluated based on results of imaging examination before surgery. 3D-digital imaging reconstruction is highly needed if there was a lower possibility to get tumor resected based on imaging data. According to pancreatic tumor size, location, and the relations with surrounding normal tissues, it requires to make precise formulation, draw a 3D icon as well as isodose curve, propose the initial dose rate of the radioactive source for fulfilling the clinical needs. Moreover, the coordinates and depth instructions of the source needle are also required. At last, the data are presented with the treatment plan form, which is the operating guide during the surgery.

Radioactive 125I seeds implantation

RIS implantation consists of percutaneous RIS implantation, percutaneous RIS implantation + biliary stenting, endoscopic ultrasonography-guided RIS implantation.

Biliary stents should be placed before the implantation of RIS. Bear in mind that observe the patient jaundice faded conditions after biliary stent placement, and it is also important to review of liver function regularly for determining the next session.

It is indispensable to monitor of vital signs during the operation, no matter in the ultrasound or CT-guided percutaneous descending RIS implantation. There should be certain person to especially observe the monitoring indicators so as to handle with the problem in time. Since many nonopen RIS implantation procedures are performed in the CT or ultrasound room, relevant materials for emergency use should be prepared since there is generally no oxygen breathing tube, rescue equipment and medication in the CT room or ultrasound room.

Percutaneously, punctured RIS implantation can be carried out under local anesthesia. If conditions permit, it is better to perform continuous epidural anesthesia or general anesthesia. The puncture accuracy can be enhanced under anesthesia, thus further favoring the implantation accuracy of RIS. Blood vessels, bile duct, and pancreatic duct trend in the puncture path should be carefully observed for avoiding accidental injury. The operation should be more careful than open surgery because percutaneous puncture process fails to stop the bleeding and deal with pancreatic fistula as well as biliary fistula. The anatomical location of the pancreas is deep, and pancreatic tumors are often located at the back side of the greater curvature of the stomach. Based on those anatomical characteristics, the puncture path often passes through the stomach, to meet the preoperative planning requirements. Therefore, patients should be given the drugs of anti-spasmolysis as well as inhibiting gastrointestinal motility if operation needed to pass through the stomach wall according to preoperative examination. So that gastrointestinal motility could be reduced, which is conducive to surgical operations.

The quality of this treatment should be verified immediately after treatment despite ultrasound or CT-guided RIS implantation. Moreover, if there was any problem, RIS should be replanted according to the instructions of the treatment planning system. It could prevent from increasing the psychological and financial burden of patients generated by the subsequent operation.

Postoperative treatment

There is no difference between open surgery and traditional surgery in the postoperative care except the necessary postoperative radiation protection. After a short period postoperatively, patients are allowed to review the CT if the general state permitted. If postoperative quality verification reveals that there is uneven distribution of RIS or the lack of local doses, it is necessary to implant RIS again or perform auxiliary plus external irradiation.

It is important to observe the vital signs of patients within 24 h after nonopen surgery. Besides, abdominal ultrasound or CT should be performed on the 1st day after surgery, for detecting bleeding and effusion timely in puncture area. If the effusion could be cleared with fluid diagnostic puncture, drainage tube can be placed and give symptomatic treatment.

For nonopen operation with puncture path avoiding gastrointestinal tract, the gastrointestinal decompression, fasting water, total parenteral nutrition, and inhibition of pancreatic enzyme secretion should be continued for 72 h. After that, if the patient's gastrointestinal function was recovered; the diet may be introduced by a gradual transition from clear liquid diet to the normal diet. For the nonopen operation with puncture path passing the gastrointestinal tract, drugs inhibiting gastric acid secretion should be added. Besides, fasting water time may be extended to 5–7 days properly.

Adverse reaction and complications

Complications associated with puncture procedures [48]

Pancreatic fistula is attributable to the injury of pancreatic duct during puncture, which can be confirmed under the following conditions: the concentration of amylase in drainage tube or ascites is more than three times higher than that of serum amylase. The drainage volume is more than 50 ml/day. The patients present the signs of peritoneal irritation and/or progressive abdominal pain, and/or imaging has confirmed its presence.[49] Pancreatic juice should be drained as soon as the confirmed presence of pancreatic fistula, and the pancreatic enzyme secretion would also be inhibited timely. By these measures, pancreatic fistula can be solved. Furthermore, the most effective method to prevent pancreatic fistula is to avoid damage to the main pancreatic duct during the puncture.[46],[50]

A small amount of bleeding (<50 ml), pain, a small amount of pneumoperitoneum, and other complications are common with slight clinical performance. These complications tend to achieve natural cure, without special treatment. However, if postoperative recurrent bleeding and (or) peritonitis continued to multiply, the surgeon should assist to diagnosis and give proper treatment.

Gastrointestinal perforation, acute pancreatitis, chylous fistula, infection, and other complications show rare occurrence rates, which can be generally cured after symptomatic treatment. However, if the condition continued to aggravate, the surgeon should assist to diagnose and give proper treatment.

RIS might migrate to the liver, lung for RIS implanted into the portal vein, and inferior vena cava caused by paracentesis. Besides, there has been no liver and lung functional lesions due to RIS migration, without the need of special treatment.[51]

Complications associated with γ-rays emitted by radioactive 125I seeds

Patients tend to present abdominal distension, nausea, vomiting, loss of appetite, and even gastrointestinal symptoms such as gastroparesis. It will be continued for a longer time in the surgery of RIS implantation compared with the traditional pancreatic cancer biliary bypass surgery. Implantation region of RIS is at short distance away from the stomach, duodenum, and bile duct anastomosis, thus leading to following radiation inflammation of the stomach, duodenum, and small intestine. However, these symptoms can be alleviated in the short term after the administration of gastrointestinal motility drugs and gastrointestinal mucosal protective agent.[52]

Patients with ascites after surgery should first receive a routine examination to determine whether there was a pancreatic fistula. If the diagnosis of pancreatic fistula was denied, patients may be given adequate nutritional support and somatostatin therapy, enabling the gradual adsorption of ascites. The reason for the ascites after the implantation for pancreatic cancer is considered as follows: (1) Poor nutritional status, low protein ascites. (2) Radioactive injury to tumor tissue from RIS produces ascites. (3) To fully reveal the tumor, separation of tumor tissue can cause damage to the small lymph tube. (4) RIS implantation area is closer to the portal vein, which may be oppressed with edema tumor tissue after radiation. Then, the poor portal system reflux and followed transient portal hypertension would also lead to ascites.[48]

Adjuvant therapy

Multidisciplinary integrated therapy is a modern modality of cancer treatment, and gemcitabine-based chemotherapy model is recommended by experts due to its greatly favorable curative effect in patients.[53] Gemcitabine of 1000 mg/m2 is intravenously administrated over 30 min, which is provided once a week for 3 weeks and then an interval of 1 week. Continuous administration of 3 cycles is considered the standard chemotherapy. However, patients with good conditions can choose the fluoropyrimidine and oxaliplatin treatment.[54]

Review and follow-up

After the implantation of RIS, the patients should be reviewed at 1, 2, and 4 months. In addition, the CT and CA19-9 examination of the pancreas should be performed to examine the effects of the treatment and to determine whether the patients developed local tumor progression, recurrence, and metastasis. Besides, patients should be reviewed once every 3–6 months for the following 2 years.

Efficacy evaluation

Therapeutic effects of pancreatic cancer treated by RIS as evaluation criterion.

Biological behavior of pancreatic cancer varies from countries and regions, and the onset age of patients with pancreatic cancer is significantly younger in China than that of in foreign countries, with an average age of 57.1 years and male/female ratio of 1.9:1. Thus, it is particularly important to affirm the therapeutic effects of RIS therapy in our country compared with the traditional treatment methods. To understand the feasibility of this treatment, the relevant literature already published in China should be retrieved, and it is also necessary to count the median survival time or survival rate of pancreatic cancer patients treated with RIS, as well as to investigate the postoperative quality of life.

Literature retrieval

CNKI database has been selected to retrieve articles from 1994 to 2016. The search terms were “pancreatic cancer + RIS,” “pancreatic cancer + 125,” “pancreatic cancer + iodine,” and “pancreatic cancer + RIS source.” A total of 170 papers have been submitted to the same treatment group published in different types of papers (such as clinical analysis and nursing experience), retaining a set of statistical data. After removing the review and basic experimental articles, 72 published papers were screened. Finally, their published data have been summarized.

Comparison data

Professional committee on pancreatic cancer of Chinese anticancer association enrolled 2340 cases suffering from pancreatic cancer in 14 tertiary hospitals covering eight provinces and two cities from 1990 to 2000. Moreover, clinical epidemiology statistics from them estimated that radical operation (including standard Whipple surgery, retained pyloric pancreaticoduodenectomy, or pancreatic cancer resection) provided a mOS of 17.1 months in 20.9% of patients, and palliative operation (including the peritumoral bypass, gastrojejunostomy, and visceral nerve alcohol occlusion) contributed to a rate of 45.8% (1071 cases) with mOS of 9 months. These data also suggested that 10.3% (242 cases) of these patients who received exploratory surgery achieved mOS of 4.5 months, while except operation, 23% (538 cases) of patients received other treatment obtained mOS of 3 months.

Patients at Stages I and II contributed to 18.4% (311 cases) of all tumor, node, and metastasis (TNM) staging cases while remaining 1381 cases (81.6%) were in Stages III and IV. According to the NCCN evaluation, 489 cases at no more than II stages were estimated to have the possibility of surgical resection, and the mOS was 17.1 months. However, 1071 cases under more than III stages received palliative surgery, providing a mOS of 9.0 months. Two hundred and forty-two cases among them received exploratory operation showed mOS of 4.5 months and the average of median survival was 8.17 months. Besides, 538 cases of these patients were considered as clinical end-stage cases, who received other treatments except surgery, while the data were not analyzed.

Impact of radioactive 125I seeds implantation on survival of patients with pancreatic cancer

A total of 1099 cases were included in relevant 72 articles, where 35 papers provided clear follow-up results and statistical survival. 541 patients were included in these 35 papers, covering 24 cases of Stage I, 127 cases of Stage II, 91 cases of Stage III, and 99 cases of Stage IV, according to TNM staging. The remaining 37 papers reported 558 cases that were at more than III stages without specific details. The median survival time was evaluated in the patients receiving RIS therapy. Patients at stage I, Stage II, presented mOS of 19.2 months, while the mOS in patients at more than stage III was 12.8 months, both of which were superior to traditional therapy. Wang et al. reported 31 cases of pancreatoduodenectomy + retroperitoneal RIS implantation for the treatment of pancreatic head cancer. A median survival time of 29 months was obtained, which was significantly higher than that of in 20 cases receiving simple pancreatoduodenectomy (mOS of 14 months).

Curative effects on pancreatic cancer pain via radioactive 125I seeds implantation

A total of 1099 cases were reported in 72 related articles, where 676 cases showed pain in the upper abdomen and lower back. 615 patients presented pain relief inordinately after the RIS therapy, with a total effective rate of 91%. The result was significantly higher than other treatments.

Acknowledgment

The authors would like to thank Gao Fei (Sun Yat-sen University Affiliated Tumor Hospital), Guo Jinhe (Southeast University Affiliated Zhongda Hospital), Hu Xiaokun (Qingdao University Affiliated Hospital), Huang Xuequan (Third Military Medical University Affiliated Southwest Hospital), Lei Guangyan (Shaanxi Provincial Cancer Hospital), Li Chengli (Shandong University Affiliated Shandong Institute of Medical Imaging), Li Maoquan (Tongji University Interventional Vascular Institute/Tongji University Affiliated Tenth Hospital in vascular surgery), Li Yuliang (Shandong University Second Hospital), Lin Zhengyu (Fujian Medical University First Hospital), Lu Ligong (Zhuhai People's Hospital), Niu Lizhi (Guangzhou Fuda Cancer Hospital), Teng Gaojun (Southeast University Affiliated Zhongda Hospital), Wang Juan (Hebei Provincial People's Hospital), Wang Junjie (Third Hospital Affiliated Peking University), Wang Ruoyu (Dalian University Affiliated Zhongshan Hospital), Wang Zhongmin (Shanghai Jiaotong University School of Medicine Ruijin Hospital), Xiang Hua (Hunan Provincial Peoples' Hospital), Zhang Jianguo (Peking University Dental Hospital), Zhang Jie (Pe king University Dental Hospital) for their kind participation in the discussion of the manuscript.

Financial support and sponsorship

This work was supported by the National Key Research and Development Program of China, (Grant number 2016YFC0103500).

Conflicts of interest

There are no conflicts of interest.

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