Pancreatic cancer is one of the common malignant tumors in the digestive system, which is characterized by late detection, early metastasis, rapid progression and poor prognosis. In recent decades, its incidence rate has been increasing year by year worldwide, ranking 13th among malignant tumors, and the mortality rate is as high as 8th among malignant tumors, with morbidity and mortality rates basically consistent, median survival period of 4-10 months, 5-year survival rate of only 5%, and poor prognosis.
Therefore, it is of great importance to study the early diagnosis of pancreatic cancer and effective comprehensive treatment modalities. Radical resection is the treatment of choice for pancreatic cancer and is considered to be the best option for prolonging the survival of pancreatic cancer, however, due to its atypical early symptoms, most patients are already in advanced stage when they are diagnosed with jaundice due to tumor invasion or compression of bile duct or painful symptoms due to invasion of surrounding tissues, and only 12%-15% of patients are feasible for radical resection.
For most of the locally advanced pancreatic cancer that cannot be resected by surgery, the main treatment methods are various kinds of in vivo and ex vivo radiotherapy and gemcitabine-based chemotherapy. Since pancreatic cancer is a tumor with a lack of blood supply, systemic systemic chemotherapy is not effective for pancreatic cancer, either as a single agent or in combination.
Although conventional radiation therapy is effective for pancreatic cancer and can improve patients’ clinical symptoms, especially relieving patients’ pain; however, due to the deep location of the pancreas and high tumor death, and the low radiation tolerance of the peri-pancreatic area such as stomach, small intestine, liver, kidney and spinal cord, it limits the dose of radiation therapy and thus cannot effectively improve the local control rate of the tumor.
Intertissue irradiation is an emerging treatment for malignant tumors, which is mainly designed by applying computerized treatment plan system (TPS) and implanting radioactive particles into tumors or tumor-infiltrated tissues according to the size and shape of tumors under the guidance of modern imaging equipment, and emitting continuous, short-distance radiation through miniature radiation sources, so that tumor tissues can be killed to the maximum extent. The micro-radiation source emits continuous, short-distance radiation, so that the tumor tissues can be killed to the greatest extent, while the normal tissues are not damaged or only slightly damaged, and finally achieve the treatment purpose.
125I particle implantation is a kind of brachytherapy, which destroys and kills tumors without damaging normal tissues by continuously emitting low-energy (27~35 keV) γ-rays, and this new minimally invasive targeted therapy technology has been widely used in the treatment of various malignant tumors and has achieved positive efficacy in clinical practice [6]. Studies have shown that the apoptosis rate of tumor cells increased 72 h after 125I particle implantation, and the apoptosis rate peaked and remained high 2 weeks after surgery.
Pancreatic cancer is a hypoxic tumor, which is highly resistant to radiation. The application of 125I particle implantation for the treatment of pancreatic cancer resulted in a decrease in the radioresistance of depleted oxygen cells, and also in the reoxygenation of depleted oxygen cells under the conditions of continuous low-dose irradiation. In addition, the effective radius of 125I particles is 1.7 cm, the half-life is 59.6 days, and the γ-rays released by implanting multiple particles can effectively cover the tumor and sub-tumor area, which can continue the radiotherapy effect on the tumor. These characteristics result in the maximum destructive killing of tumor cells due to the radiation effect, thus achieving the purpose of cure.
At the same time, because the dose distribution around the radiation source decreases in an inverse proportion to the square of the distance from the radiation source, the neighboring tissues, such as the intestine, mesenteric arteries and veins, are less affected, which reduces the incidence of complications.
In contrast, 125I particle implantation therapy has advantages that external irradiation does not have.
(1) The treatment is precisely positioned and fits well with the tumor shape;
(2) Rapid reduction of irradiation dose beyond the particle implantation range;
(3) High dose in the target area without increasing the damage to normal tissues;
(4) Computerized treatment planning with more uniform and reasonable dose distribution;
(5) Complementary effect with surgery and chemotherapy;
(6) The effect of protecting the function and morphology of the body. Xie Xiaoxi et al. retrospectively analyzed the data of 48 patients with various malignant tumors treated by CT-guided 125I particle implantation, and all patients were successfully implanted with 125I particles, among which 43 patients were followed up for 1~13 months, and the total clinical efficiency was 72%, and in more cases, the tumor shrank significantly or disappeared completely within one half-life (1-2 months) after 125I particle implantation, which proved that 125I particles have good tumor local control rate for many kinds of malignant tumors.
The Center for Cancer Control of Sun Yat-sen University performed CT-guided radioactive particle implantation treatment on 26 cases of pancreatic cancer, and the follow-up was performed by imaging examination, and the change of lesion size before and after radioactive particle implantation was used as the criterion to judge the efficacy, and the recent effective rate was 57.7%, which was satisfactory. Luo Kaiyuan et al. reported that 125I particle inter-tissue implantation for pancreatic cancer also had significant effect on the relief of advanced tumor pain.
The implanted particles can kill a large number of tumor cells within the implantation area and produce damage to the unkilled cells, while the reduction of tumor load may increase the sensitivity of these cells to chemotherapeutic drugs, which is conducive to further comprehensive treatment of tumor patients.
Wang Zhongmin et al. performed CT-guided 125I particle implantation combined with gemcitabine and fluorouracil arterial perfusion treatment in 31 cases of unresectable advanced pancreatic cancer for 3-4 cycles, with a total follow-up of 2-25 months after treatment to observe the safety and clinical efficacy of its treatment for pancreatic cancer. The total effective rate of CT follow-up at 2 months after surgery was 61.3%, and the median survival time of the whole group was 10.31 months. No adverse effects such as upper gastrointestinal bleeding, pancreatitis and pancreatic fistula were observed in the whole group during the follow-up period.
125I particles can be implanted under direct surgical vision, CT, ultrasound or lumpectomy guidance. In recent years, multilayer spiral CT volume scanning with fast imaging speed and clear images provides a good means for CT-guided particle implantation therapy, which is currently the best method for pancreatic puncture guidance.
CT-guided implantation of radioactive particles for treatment has the following advantages.
(1) It makes full use of the TPS of radioactive particles, which can reconstruct the tumor in three dimensions according to the CT image data, observe the size, morphology and location of the tumor, make preoperative preparations for selecting the puncture point and designing the needle route, determine the direction and depth of the needle, and avoid the blood vessels, pancreatic duct and surrounding important organs in the pancreas;
(2) Input the prescribed dose of particle implantation and the 125I particle activity used into TPS to calculate the ideal particle distribution map within the target area;
(3) Adjust the needle direction by changing different body positions according to the CT real-time images to avoid damage to blood vessels and vital organs as much as possible to improve the efficacy and reduce complications;
(4) After the particle implantation, the implanted tumor target volume will be scanned and checked by CT, and if the particle distribution is not uniform or there is a blank target area, the particles can be supplemented in time to reduce the missing target volume as much as possible;
(5) The duration of local tumor treatment is longer and the dose of radiation therapy is relatively low, so the damage to surrounding normal tissues is smaller and the killing effect on tumor cells is strong.
In conclusion, CT-guided 125I particle implantation technique for pancreatic cancer treatment is a simple, minimally invasive and safe technique with positive clinical efficacy. However, the biggest problem of this technique is that the intraoperative guided radioactive particle implantation technique is not accurate enough, and the spatial distribution of particles still has a large error with the preoperative treatment plan, which directly affects the treatment effect. This problem is illustrated by the occurrence of too dense particle distribution (interval <1>1.5 cm).
The reasons for the deviations in the position of the implanted particles were analyzed as.
(1) CT guidance is not really real time, if B-type ultrasound guidance is used, it may reduce the error, but since the pancreas is an interperitoneal organ and is obscured by the stomach and intestines in front, this is also a drawback of using ultrasound guidance;
(2) When the puncture needle encounters the pancreatic duct and vessels, it forces to change the direction of puncture;
(3) Wandering of the implanted particles occurs, especially in cystic lesions, which is prone to occur. As a peritoneal interstitial organ, the pancreas is deeply located, and repeated puncture of the puncture needle is also prone to needle tract metastasis and peritoneal metastasis. Therefore, there are many aspects of the status and role of 125I particle implantation in the comprehensive treatment of pancreatic cancer that deserve further study.