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ORIGINAL ARTICLE
Year : 2021  |  Volume : 17  |  Issue : 3  |  Page : 702-706

Advantages of interstitial radioactive seed implantation for the treatment of Stage III pancreatic cancer


1 Department of Gastrointestinal Surgical, Third Hospital of Jilin University, Changchun, China
2 Department of Ultrasound, Third Hospital of Jilin University, Changchun, China

Date of Submission16-Jun-2020
Date of Decision20-Jan-2021
Date of Acceptance08-Mar-2021
Date of Web Publication9-Jul-2021

Correspondence Address:
Dongyan Yang
Department of Ultrasound, Third Hospital of Jilin University, 126 Xiantai St., Changchun - 130 031
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_803_20

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 > Abstract 


Objective: The objective of the study was to identify the advantages of interstitial radioactive seed implantation for the treatment of Stage III pancreatic cancer.
Materials and Methods: Clinical data of 160 patients with pancreatic cancer implanted with radioactive seeds were retrospectively analyzed. Patients were grouped according to tumor size, lymph node metastasis, and tumor invasion to important blood vessels, and survival time statistics were obtained.
Results: The mean postoperative survival time (months) was 24.80 for Stage I, 12.89 for Stage II, 13.51 for Stage III, and 7.49 for Stage IV patients, and the difference between Stage II and Stage III patients was not statistically significant. The efficacy of radioactive seed implantation therapy for pancreatic cancer was strongly associated with tumor size and number of lymph node metastases but not significantly associated with tumor invasion to blood vessels.
Conclusions: Radioactive seed implantation obviously advantageous for the treatment of Stage III pancreatic cancer.

Keywords: Pancreatic cancer, radioactive seeds, survival time, tumor node metastasis classification


How to cite this article:
Gai B, Li Q, Shao P, Yang D. Advantages of interstitial radioactive seed implantation for the treatment of Stage III pancreatic cancer. J Can Res Ther 2021;17:702-6

How to cite this URL:
Gai B, Li Q, Shao P, Yang D. Advantages of interstitial radioactive seed implantation for the treatment of Stage III pancreatic cancer. J Can Res Ther [serial online] 2021 [cited 2021 Aug 5];17:702-6. Available from: https://www.cancerjournal.net/text.asp?2021/17/3/702/321037




 > Introduction Top


The incidence of pancreatic cancer is continuously increasing. Over the past 50 years, China has conducted three retrospective sampling surveys regarding the cause of death, and pancreatic cancer has climbed from a relatively low cause at 10th to the 7th highest cause of cancer-related deaths in China.[1],[2],[3],[4] In the epidemiological characteristic analysis of malignant tumor mortality in Chinese residents in 2015, pancreatic cancer had moved up to the 6th place in the ranking, with crude mortality of 5.20/100,000.[5] Surgery is the best treatment method for pancreatic cancer. With technological development and advanced treatment concepts, surgery has become safer and has had significantly lower perioperative mortality. Meanwhile, with the advancement of imaging technology, accurate preoperative evaluation of tumors can be achieved, increasing the resection rate of pancreatic tumors. However, our analysis of China's big data reports found no significant improvement in survival time of patients with pancreatic cancer over the past 30 years.[6],[7] Since 2000, interstitial implantation of radioactive seeds has been widely practiced in China to treat solid malignant tumors and has gained satisfactory outcomes.[8],[9] The 160 patients with pancreatic cancer in this study were treated with ultrasound-guided percutaneous interstitial radioactive seed implantation. This minimally invasive method greatly improved patients' quality of life and survival and showed obvious advantages in treating patients with Stage III pancreatic cancer.

The mean survival period after radioactive seed implantation was 13.51 months, which was better than that of stage II cases, providing effective treatment for patients with pancreatic cancer that could not be surgically resected owing to the invasion of important blood vessels by the pancreatic tumor.


 > Materials and Methods Top


General data

Clinical and follow-up data of 160 patients who underwent ultrasound-guided percutaneous radioactive seed implantation as the primary treatment for pancreatic cancer from January 2008 to July 2019 in China-Japan Union Hospital of Jilin University were retrospectively analyzed. Inclusion criteria were as follows: 1. preoperative pathological diagnosis of pancreatic ductal adenocarcinoma by percutaneous fine needle biopsy; 2. patients who received radioactive seed implantation as the primary treatment without other antitumor treatments after being diagnosed with pancreatic cancer; 3. patients with good general condition to tolerate the seed implantation therapy; 4. patients who had finished more than two cycles of gemcitabine-based chemotherapy after the seed implantation therapy; 5. patients with a life expectancy of ≥3 months; 6. patients not contraindicated for percutaneous puncture surgery; and 7. patients with complete clinical and follow-up data. Exclusion criteria were as follows: 1. patients requiring open surgery for radioactive seed implantation; 2. patients requiring surgical procedures for other severe clinical symptoms caused by pancreatic cancer such as gastrointestinal obstruction and biliary obstruction; 3. patients with extremely poor general condition to tolerate seed implantation therapy; and 4. patients with maximum pancreatic tumor diameter of ≥7 cm.

In this study, 109 male and 51 female patients with a mean age of 61.75 ± 9.85 (range, 32–85) years were included. Eighty-four patients had developed jaundice when seeking medical care and all of them were treated for jaundice before radioactive seed implantation. The treatment included percutaneous transhepatic cholangiography and stent implantation in 55, percutaneous transhepatic biliary drainage in 21, and biliary drainage under duodenoscope in 8 patients. Tumor node metastasis (TNM) tumor classification was Stage I in 10 patients, Stage II in 18, Stage III in 95, and Stage IV in 37. General data and tumor stage of patients are shown in [Table 1]. Based on the pancreatic tumor size and lymph node metastasis, Stage III patients were grouped into No. 1–No. 12. No. 1–No. Three groups were in Stage III (T1-3-N2-M0), whereas No. 4–No. 12 groups were in Stage III (T4-anyN-M0). The grouping is shown in [Table 2]. Imaging examination was used to detect the presence and number of lymph node metastases. T-test was used to compare survival time between groups, and result of P < 0.05 was considered statistically significant.
Table 1: General data and tumor stage of patients

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Table 2: Grouping of Stage III patients

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Operation of radioactive seed implantation

Three-dimensional digital image of tumor and surrounding areas with metastatic lymph nodes was reconstructed preoperatively based on imaging data. According to the size, location, and relationship with surrounding normal tissues of the pancreatic tumor lesion and metastatic lymph nodes, we precisely formulated and drew a 3D icon as well as isodose curve. We proposed the initial dose rate of the radioactive source to fulfill the clinical needs, as well as puncture site coordinates and depth instructions for the source needle. Finally, the preoperative treatment plan was prepared, which is the operating guide for surgical procedures. The sealed radionuclide 125I radioactive seed was adopted, which is a 4.5 × φ0.8-mm cylinder, with gamma-ray energy of 27.4–31.5 KeV, a half-life of 59.6 days, tissue penetration distance of 1.7 cm, half value layer of 0.025-mm lead, a surface wrapped with titanium alloy, and source activity of 14.8–29.6 MBq. Seed implantation was performed under continuous epidural or general anesthesia, because the puncture accuracy can be enhanced under anesthesia, thus further favoring the implantation accuracy. Blood vessels, bile duct, and pancreatic duct in the puncture path should be carefully observed during the procedure to avoid accidental injury. The quality of this treatment should be verified immediately after treatment. Moreover, if verification shows therapeutic cold spots, radioactive seeds should be replanted to an effective therapeutic dose according to the instructions of the treatment planning system. Vital signs and symptoms of patients should be observed within 24 h postoperatively. Abdominal ultrasound or computed tomography (CT) should be performed on the 1st day postoperatively for the timely detection of bleeding and effusion in the puncture area. Large effusions could be cleared with diagnostic puncture. If required, a drainage tube could be placed under an ultrasound-guided puncture.

Review and follow-up

After the radioactive seed implantation, patients should be followed up at the hospital at 1, 2, and 4 months. In addition, examinations including chest and abdominal CT and/or abdominal ultrasound and CA 19-9 should be performed to examine the treatment effects and determine whether patients had developed local tumor progression, recurrence, or metastasis. Besides, patients should be followed up once every 3–6 months for the following 2 years. Gemcitabine-based chemotherapy was started within 1 week after seed implantation. All patients received 2–6 cycles of chemotherapy.


 > Results Top


All patients underwent seed implantation according to the preoperative treatment plan. Their mean postoperative survival time in different stages and groups is shown in [Table 3]. The P value for survival time was 0.0022 between Stages I and II, 0.8230 between Stages II and III, and 0.0026 between Stages III and IV; 0.0115 between stage T4-anyN-M0 and Stage I and 0.6561 between stage T4-anyN-M0 and Stage II; 0.6921 between Stage IA and group No. 4; 0.1442 between Stage IB and group No. 7; 0.1151 between Stage IIA and group No. 10; and 0.1138 between Stage IIB and combined data of groups No. 5, No. 8, and No. 11.
Table 3: Mean survival time of patients in different stages and groups

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The mean survival time was 35.23 ± 19.67 (months) for Stages I, II, and III patients with maximum tumor diameter of ≤2 cm (Group D1: IA, No. 1, No. 4, No. 5, and No. 6). The mean survival time was 13.60 ± 7.94 (months) in patients with maximum tumor diameter of >2 cm and ≤4 cm (Group D2: IB, IIB-T2N1M0, No. 2, No. 7, No. 8, and No. 9). The mean survival time was 10.02 ± 4.79 (months) in patients with maximum tumor diameter of >4 cm (Group D3: IIA, IIB-T3N1M0, No. 3, No. 10, No. 11, and No. 12). The P<0.0001 between Groups D1 and D2 and P=0.0054 between Group D2 and D3.

The mean survival time was 17.24 ± 12.82 (months) for Stages I, II, and III patients without lymph node metastasis (Group N0: IA, IB, IIA, No. 4, No. 7, and No. 10); 9.63 ± 3.79 (months) in patients with 1–3 regional lymph node metastases (Group N1: IIB, No. 5, No. 8, and No. 11); and 7.41 ± 2.50 (months) in patients with ≥4 regional lymph node metastases (Group N2: No. 1, No. 2, No. 3, No. 6, No. 9, and No. 12). The P = 0.0121 between Groups N0 and N1 and 0.0179 between Groups N1 and N2.


 > Discussion Top


Surgery is the primary treatment for pancreatic cancer. However, pancreatic cancer commonly develops with atypical symptoms and rapid progression; therefore, majority of patients presenting to the hospital have lost the chance of surgery. Therefore, it is difficult to treat and has poor therapeutic outcomes.[10],[11] Radiotherapy, chemotherapy, immunotherapy, and symptomatic treatment are used for patients who have lost the chance of surgery to improve their survival time and quality of life to certain extents.[12],[13],[14],[15] In this study, interstitial radioactive seed implantation was found to be an effective treatment for patients with pancreatic cancer who have lost the chance of surgical resection or cannot tolerate the surgery.[9] In radioactive seed implantation therapy for malignant tumors, radioactive sources are directly implanted into the tumor tissue. The seeds continuously release low-energy rays to kill and inactivate the tumor tissues. However, the exact mechanism of killing tumor cells through radioactive seeds remains unknown. Currently, studies suggest that it may be associated with low-energy rays that induce tumor cell apoptosis, promote cell cycle arrest, and inhibit tumor angiogenesis.[16],[17]

We used interstitial radioactive seed implantation therapy for pancreatic cancer. The mean postoperative survival time (months) was 24.80 for Stage I patients, 12.89 for Stage II, 13.51 for Stage III, and 7.49 for Stage IV. Jin et al.[7] reported that the median survival time of 1657 patients with pancreatic cancer who underwent radical surgery was 19.6 months, and the median survival time of 271 patients who received palliative treatment was 7.2 months. The postoperative survival times for our Stage I and Stage II patients were similar to those of patients who underwent radical surgery, and our Stage III and Stage IV patients had better mean survival time than those who received palliative treatments. The TNM tumor classification primarily aims to guide clinical treatment and judge the prognosis. Radioactive seed implantation was used to treat pancreatic cancer. No statistical difference was noted in the survival time between Stage II and Stage III patients (P = 0.8230); however, Stage III patients had longer mean survival time than Stage II patients, which may be caused by the following.

In order to identify the characteristics of radioactive seed implantation for the treatment of pancreatic cancer, Stage I, Stage II, and Stage III patients were classified into three groups, according to classification criteria of T1–T3 in the TNM classification of pancreatic cancer in National Comprehensive Cancer Network (NCCN) guidelines: D1 with maximum tumor diameter of ≤2 cm, D2 with maximum tumor diameter of >2 and ≤4 cm, and D3 with maximum tumor diameter of >4 cm. Significant difference was observed in the survival time between groups D1 and D2 and between Groups D2 and D3. This shows that the efficacy of radioactive seed implantation therapy for pancreatic cancer is strongly associated with tumor size. The larger is the tumor, the poorer is the efficacy.

Based on pancreatic tumor size and lymph node metastasis, Stage III patients were classified into Groups No. 1–No. 12 [Table 2]. No significant difference was found in the survival time between Stage IA and group No. 4, between Stage IB and group No. 7, between Stage IIA and group No. 10, and between Stage IIB and combined data of groups No. 5, No. 8, and No. 11. The above groups were chosen for comparison because they were similar in tumor size, lymph node metastasis, and distant metastasis. The only difference was that Stage IA, Stage IB, Stage IIA, and Stage IIB patients had no tumor invasion of the celiac trunk, superior mesenteric artery and vein, common hepatic artery, portal vein, and other blood vessels, whereas patients in groups No. 4, No. 7, No. 10, and No. 5 + No. 8 + No. 11 had tumor contact with important arteries of >180° and/or invasion and occlusion of important veins, and these vessels were not suitable for vascular reconstruction, i.e., surgical resection. No statistical significance was observed between groups, indicating that the therapeutic effect of radioactive seed implantation is not related to whether blood vessels are invaded by tumors.

In the NCCN guidelines for pancreatic cancer, the TNM tumor classification is a staging method with surgery as the primary treatment, and surgical resection will not be considered if tumors invade the celiac trunk, superior mesenteric artery and vein, common hepatic artery, portal vein, and other important blood vessels around the pancreas and if solid tumors are in contact with important arteries for >180° and/or important veins are invaded, occluded, and not suitable for vascular reconstruction. Besides the tumor size, such primary tumors are classified into T4 in Stage III, namely, T4-anyN-M0. In patients not suitable for surgical resection of primary tumor, the tumor progresses rapidly; therefore, patients have significantly shorter survival time than Stage I and Stage II patients who are suitable for surgical resection. Radioactive seed implantation therapy is a local and minimally invasive treatment for tumors. Its efficacy is strongly associated with tumor size but not significantly related to whether the tumor invades the blood vessels. These characteristics lead to unique advantages of the radioactive seed implantation in treating Stage III T4-anyN-M0 pancreatic cancer. For patients not suitable for surgery due to blood vessel metastasis of the pancreatic cancer shown in the preoperative imaging, seed implantation therapy has good efficacy in patients with Stage III T4-anyN-M0 pancreatic cancer.

In NCCN Guidelines 2018 V1, the TNM classification was greatly revised from its previous versions. For instance, the new TNM classification divides lymph node metastasis into N1 and N2 and puts more emphasis on the number of lymph node metastases. The previous Stage IIB T1-3-N2-M0 is classified as Stage III. The impact of lymph node metastasis on tumor prognosis is emphasized.[18] Based on the number (N) of lymph node metastases, Stage I–III patients were divided into three groups: N0, without lymph node metastasis (IA, IB, IIA, No. 4, No. 7, and No. 10); N1 with 1–3 regional lymph node metastases (IIB, No. 5, No. 8, and No. 11); N2, without <4 regional lymph node metastases (No. 1, No. 2, No. 3, No. 6, No. 9, and No. 12). The difference in survival time was significant between groups N0 and N1 and between N1 and N2, showing that the existence and number of lymph node metastases have significant impacts on prognosis. During the radioactive seed implantation therapy for pancreatic cancer, we implanted seeds into the primary pancreatic lesions, as well as metastatic lymph nodes diagnosed by imaging. However, unlike the en bloc resection and radical lymph node dissection to remove most of the potential small metastatic lymph nodes and lesions, this therapy is not applicable for small and micrometastatic lymph nodes and lesions that cannot be detected by imaging, and this is an obvious defect of this therapy. How to treat micrometastatic lymph nodes and lesions that cannot be detected by imaging remains to be investigated in future studies.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Ma C, Jiang YX, Liu SZ, Quan PL, Sun XB, Zheng RS, et al. Trend and prediction on the incidence of pancreatic cancer in China. Zhonghua Liu Xing Bing Xue Za Zhi 2013;34:160-3.  Back to cited text no. 1
    
2.
Gu K, Wu CX, Bao PP, Wang CF, Peng P, Gong YM, et al. Incidence of pancreatic cancer in Shanghai: A current, retrospective and comparative exploration. J Surg Concepts Pract 2009;14:510-5.  Back to cited text no. 2
    
3.
Chen Z. The Third National Death Survey Report. Beijing: Peking Union Medical College Publication House; 2008.  Back to cited text no. 3
    
4.
Zang WD, Miao SJ. Analysis on epidemic characteristics of cancer death rate in China. Chin J Health Educ 2009;25:246-8.  Back to cited text no. 4
    
5.
Lan L, Zhao F, Cai Y, Wu R, Meng Q. Epidemiological analysis on mortality of cancer in China, 2015. Chin J Epidemiol 2018;39:32-4.  Back to cited text no. 5
    
6.
Zhang QH, Ni QX. Clinical analysis of 2340 cases of pancreatic cancer. Natl Med J China 2004;84:214-8.  Back to cited text no. 6
    
7.
Jin G, Shao Z, Hu XG, Zhang YJ, Liu R, Zhou YQ, et al. Efficacy and prognosis analysis of 2061 cases of pancreatic cancer resection. Chin J Pancreatol 2013;13:1-4.  Back to cited text no. 7
    
8.
Wang J, Chai S, Zheng G, Jiang Y, Ji Z, Guo F, et al. Expert consensus statement on computed tomography-guided (125) I radioactive seeds permanent interstitial brachytherapy. J Cancer Res Ther 2018;14:12-7.  Back to cited text no. 8
    
9.
Gai B, Zhang F. Chinese expert consensus on radioactive 125I seeds interstitial implantation brachytherapy for pancreatic cancer. J Cancer Res Ther 2018;14:1455-62.  Back to cited text no. 9
    
10.
Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin 2011;61:69-90.  Back to cited text no. 10
    
11.
Seufferlein T, Bachet JB, Van Cutsem E, Rougier P, Group EG. Pancreatic adenocarcinoma: ESMO-ESDO clinical practice guidelines for diagnosis, treatment and follow-up. Ann Oncol 2012;23 Suppl 7:vii33-40.  Back to cited text no. 11
    
12.
Lominska CE, Unger K, Nasr NM, Haddad N, Gagnon G. Stereotactic body radiation therapy for reirradiation of localized adenocarcinoma of the pancreas. Radiat Oncol 2012;7:74.  Back to cited text no. 12
    
13.
Heinemann V, Boeck S, Hinke A, Labianca R, Louvet C. Meta-analysis of randomized trials: Evaluation of benefit from gemcitabine-based combination chemotherapy applied in advanced pancreatic cancer. BMC Cancer 2008;8:82.  Back to cited text no. 13
    
14.
Evans A, Costello E. The role of inflammatory cells in fostering pancreatic cancer cell growth and invasion. Front Physiol 2012;3:1-7.  Back to cited text no. 14
    
15.
Wolfgang CL, Herman JM, Laheru DA, Klein AP, Erdek MA, Fishman EK, et al. Recent progress in pancreatic cancer. CA Cancer J Clin 2013;63:318-48.  Back to cited text no. 15
    
16.
Herfarth KK, Debus J, Lohr F, Bahner ML, Fritz P, Höss A, et al. Extracranial stereotactic radiation therapy: Set-up accuracy of patients treated for liver metastases. Int J Radiat Oncol Biol Phys 2000;46:329-35.  Back to cited text no. 16
    
17.
Ma ZH, Yang Y, Zou L, Luo KY. 125I seed irradiation induces up-regulation of the genes associated with apoptosis and cell cycle arrest and inhibits growth of gastric cancer xenografts. J Exp Clin Cancer Res 2012;31:61.  Back to cited text no. 17
    
18.
National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Pancreatic Adenocarcinoma; 2018 Version I. Available from: https://www.nccn. org/patients. [Last accessed on 2021 Mar 20].  Back to cited text no. 18
    



 
 
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