Home About us Editorial board Ahead of print Current issue Search Archives Submit article Instructions Subscribe Contacts Login 

 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 17  |  Issue : 3  |  Page : 720-725

The clinical efficacy of computed tomography-guided 125I particle implantation combined with arterial infusion chemotherapy in the treatment of pancreatic cancer


Department of Medical Oncology, Affiliated Zhongshan Hospital of Dalian University; The Key Laboratory of Biomarker High Throughput Screening and Target Translation of Breast and Gastrointestinal Tumor, Dalian University, Dalian, P. R. China

Date of Submission03-May-2020
Date of Decision13-Oct-2020
Date of Acceptance23-Feb-2021
Date of Web Publication9-Jul-2021

Correspondence Address:
Ruoyu Wang
Department of Medical Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001
P. R. China
Zhe Wang
Department of Medical Oncology, Affiliated Zhongshan Hospital of Dalian University, Dalian 116001
P. R. China
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_563_20

Rights and Permissions
 > Abstract 


Aims: This study aimed to investigate the clinical value of 125I radioactive particle implantation combined with regional arterial chemotherapy perfusion in the treatment of pancreatic cancer.
Subjects and Methods: The clinical data of 23 patients with pancreatic cancer were retrospectively analyzed, and the patients were divided into two groups. In the observation group, 11 patients were injected with radioactive particles in combination with regional arterial chemotherapy. In the control group, 12 patients were treated with simple regional arterial perfusion chemotherapy. Curative effect, pain relief, survival period, and adverse reactions were compared between the two groups.
Results: The proportion of patients was significantly higher in the observation group (complete remission + partial remission) (72.73%) than in the control group (41.67%). The 6-month and 9-month survival rates in the experimental group were 91.7% and 50%, respectively, while those in the control group were 63.6% and 18.2%, respectively, with significantly statistical difference. The 12-month survival rate in the experimental group was 16.7% and was significantly higher than that in the control group (8.3%). The experimental group should greater improvement in pain symptoms than the control group, and there was no statistical difference between the two groups except in complications of 125I radioactive particle implantation.
Conclusions: We conclude that 125I radioactive particle implantation combined with regional arterial perfusion chemotherapy is an effective and comprehensive treatment for advanced pancreatic cancer.

Keywords: Pancreatic cancer, perfusion chemotherapy, radioactive particles


How to cite this article:
Yang L, Li C, Wang Z, Wu J, Zhou J, Wang R. The clinical efficacy of computed tomography-guided 125I particle implantation combined with arterial infusion chemotherapy in the treatment of pancreatic cancer. J Can Res Ther 2021;17:720-5

How to cite this URL:
Yang L, Li C, Wang Z, Wu J, Zhou J, Wang R. The clinical efficacy of computed tomography-guided 125I particle implantation combined with arterial infusion chemotherapy in the treatment of pancreatic cancer. J Can Res Ther [serial online] 2021 [cited 2021 Aug 5];17:720-5. Available from: https://www.cancerjournal.net/text.asp?2021/17/3/720/321034




 > Introduction Top


Approximately 80% of patients with pancreatic cancer show moderate and advanced stage disease at the initial diagnosis, making them no longer suitable for surgery.[1] Although multiple novel technologies have been applied to the treatment of pancreatic cancer, the patients' survival rate has not improved significantly. The 5-year survival rate remains at approximately 5%, and the median survival time is merely 3–4 months. Most of the patients with surgically unresectable lesions die within 1 year.[2] Gemcitabine alone or combination with other regimens are currently the first-line treatment for pancreatic cancer. Compared with systemic intravenous chemotherapy, arterial infusion chemotherapy can increase the drug concentration, thereby effectively improving the clinical benefit rate of patients.[3] Recent studies suggested that the implementation of 125I radioactive particle implantation in the treatment of pancreatic cancer demonstrated a better effect on inhibiting tumor growth and managing cancer pain.[4],[5] In this study, 23 patients with pancreatic cancer were admitted as the research objects. The patients were subsequently treated with arterial infusion chemotherapy combined with 125I radioactive particle implantation, the clinical efficacy of which was proven superior.


 > Subjects and Methods Top


Patient information

This study retrospectively analyzed the clinical data of patients with pancreatic cancer treated at the Affiliated Zhongshan Hospital of Dalian University between June 2016 and June 2018. Among the patients, 15 were men and 8 were women, the ages of whom ranged from 57 to 76 years. Patients whose lesion pathology were confirmed by biopsy, whose surgical evaluation showed no indications for radical surgery, and with at least one measurable target lesion were included in the study. The patients were subsequently divided into an observation group and a control group. The observation group comprised seven Tumor, Node, Metastasis (TNM) Stage III and four TNM Stage IV patients, whereas the control group comprised nine TNM Stage III and three TNM Stage IV patients. There were no significant differences between the TNM staging of the two groups.

Equipment

A Toshiba computed tomography (CT) simulator, a particle implantation planning system from Beijing Astro Technology Ltd. Co., workstations with medical image management and radiotherapy planning systems, a Mick particle implantation gun, a particle implantation positioning and navigation system, and an X-ray digital subtraction angiography system from Siemens, Germany, were used in the study.

Treatment methods

Observation group

Participants in the observation group underwent 125I radioactive particle implantation combined with arterial infusion chemotherapy. The specific 125I radioactive particle implantation steps were as follows: (1) the target area was determined on the CT scan before implantation, and a preoperative plan was created [Figure 1]. Three days before the procedure, the patients were instructed to ingest only clear fluids. Meanwhile, enteric antibiotics were administered orally. At 24 h before surgery, patients were required to fast for 24 h, during which drugs inhibiting pancreatic secretion, proton pump inhibitors, and nutrition support were administered intravenously. At 3 h before the surgery, a diluted contrast agent was administered orally, while a hemostatic medication was injected intravenously. During the procedure, particle implantation was performed under CT guidance and template assistant [Figure 2] and [Figure 3]. Once completed, CT scan of the surgical area was performed, the images of which were imported into the radiotherapy treatment planning system to calculate the dose distributions of the target as well as the surrounding normal tissue. Three days postimplantation, CT scan was performed to evaluate postoperation plan [Figure 4]. The results indicated that the dose received by 90% of the target volume, D90, was 115.6 ± 18.6 Gy of the prescribed dose; the percentage of the target volume that received 100% of the prescribed dose, V100, was 88.9 ± 10.4%; V150 = 54.2 ± 12.8%; conformal index = 0.74 ± 0.11; external index = 0.19 ± 0.22; heterogeneity index = 0.37 ± 0.1; and the duodenum D2cc = 35.6 ± 20.7%. After the implantation, the patients were instructed to rest in bed and fast for 24 h, during which drugs that inhibit pancreatic secretion, proton pump inhibitors, hemostatic drugs, and nutrition support were administered intravenously. Three weeks after the procedure, patients with pancreatic head carcinoma underwent gastroduodenal and superior mesenteric arterial infusion chemotherapy, those with pancreatic body and tail carcinoma underwent splenic arterial infusion chemotherapy, and those whose disease were accompanied with liver metastases underwent hepatic arterial infusion chemotherapy. The infusion chemotherapy medications used were as follows: gemcitabine (Harbin Gloria Pharmaceuticals Co., Ltd., State Drug No. H20040958) at one-third dose of 1000 mg/m2 and lobaplatin (Hainan Chang 'an International Pharmaceutical Co., Ltd., State Drug No. H20050309) at one-third dose of 50 mg/m2. The chemotherapy courses were administered at an interval of 3 or 4 weeks according to the patient's tolerance for a total of four courses.
Figure 1: CT image of preimplantation plan. Red cycle represents GTV. Yellow cycle represents CTV

Click here to view
Figure 2: Coplanar template assistant radioactive seed implantation

Click here to view
Figure 3: CT image of the needle location before seed implantation

Click here to view
Figure 4: CT image at 3 days post- implantation

Click here to view


Control group

Patients in the control group were treated with arterial infusion chemotherapy alone. The treatment was performed as follows: In the interventional therapy theater, after femoral artery puncture was conducted following the Seldinger technique, patients with pancreatic head carcinoma were treated with gastroduodenal and superior mesenteric arterial infusion chemotherapy, those with pancreatic body and tail carcinoma were treated with splenic arterial infusion chemotherapy, and those whose diseases were accompanied with liver metastases were treated with hepatic arterial infusion chemotherapy. The same chemotherapy drugs and courses were applied to these patients.

Evaluation indices

The results of a recent preoperative abdominal CT or magnetic resonance imaging examination performed not more than 2 weeks ago were used to determine the target lesion at baseline. (1) A target lesion evaluation was first conducted at 4 weeks after treatment, followed by once every 8 weeks. Subsequently, during the follow-up period, a review examination was performed once every 3 months. Based on the Response Evaluation Criteria in Solid Tumors,[6] the clinical outcomes of the patients were categorized into partial remission (PR), complete remission (CR), stable condition (SD), and progressive disease (PD). PR was defined as a 30% reduction in the sum of the critical radii of all target lesions. CR was defined as the disappearance of all target lesions, and additionally, a reduction in the short-axis lengths of pathological lymph nodes to <10 mm. Meanwhile, PD was defined as a 20% increase in the minimum sum of the radii of all target lesions and a >5 mm increase in the absolute value. SD was defined as follows: the minimum sum of the radii of all target lesions that did not satisfy either the PD criteria or the remission criteria. The total effective rate of the treatment was then calculated as total effective rate = CR + PR. The objective response rate was defined as the proportion of patients whose CR and PR were confirmed (i.e., CR + PR) at least 4 weeks after the procedure. The disease control rate was defined as the proportion of those patients whose tumor remission was verified (CR + PR) as well as those patients whose outcome was SD after at least 4 weeks of drug administration (i.e., CR + PR + SD). (2) Pain severity was assessed using the numeric rating scale (NRS). The pain degree was divided into ten levels from 0 to 10; the higher the level, the more severe the pain. (3) The physical condition of the patients was assessed using the Karnofsky Performance Scale with a total score of 100; the higher the score, the better the patient's physical condition. (4) The clinical benefits of the patients 1 month after the treatment were assessed according to the clinical benefit response proposed by Burris et al.[7] (5) Patients' quality of life before and after treatment was assessed using the European Organization for Research and Treatment of Cancer Quality of Life questionnaire – C30:[8] The median survival time, 2-year survival rate, and progression-free survival of the patients were identified during the follow-up period: The follow-up period ranged from the initiation of treatment until patient's death. The deadline for the last follow-up was June 30, 2018.

Statistical analysis

All data were processed in the SPSS 17.0 software package (IBM, New York, USA) was used for analysis. Measurement data were expressed as “mean ± standard deviation.” The correlation of the short-term efficacies of the two groups was analyzed using the rank sum and the Chi-square tests. Comparison between multiple groups was conducted using the least significant difference test. Survival analysis was carried out using the Kaplan–Meier estimator. Differences were statistically significant if P < 0.05.


 > Results Top


Comparison of the treatment efficacy between the two groups

Comparison of (CR + PR) % between the two groups suggested that the (CR + PR) % of the observation group was substantially higher than that of the control group [P < 0.05, [Table 1]].
Table 1: Comparison of the treatment efficacy between the two groups

Click here to view


Comparison of the pain relief between the two groups

Before the treatment, the pain scores of the two groups were not significantly different (P > 0.05). In details, it was composed of 11 and 12 patients in observation and control group, respectively. It was consisted of five patients suffering severe cancer pain, two patients suffering moderate cancer pain and three patients suffering middle cancer pain in observation group before treatment. On the contrary, although after treatment, the pain of both groups was relieved to a certain extent, the degree of pain relief experienced by the observation group was significantly higher than that by the control group, the difference of which was statistically significant, as shown in [Table 2].
Table 2: Comparison of pain scores between the two groups

Click here to view


Comparison of the clinical benefits between the two groups

The clinical benefit response survey indicated that there were statistically significant differences between the clinical benefits of the two groups (P < 0.05). The clinical benefits received by the observation group were better than those received by the control group, as shown in [Table 3]. In details, the proportion of patients was significantly higher in the observation group (CR + PR) (72.73%) than in the control group (41.67%). The 6-month and 9-month survival rates in the experimental group were 91.7% and 50%, respectively, while those in the control group were 63.6% and 18.2%, respectively, with significantly statistical difference. The 12-month survival rate in the experimental group was 16.7% and was significantly higher than that in the control group (8.3%).
Table 3: Clinical benefits received by the two groups

Click here to view


Survival analysis

The 6-month, 9-month, and 1-year cumulate survival rates and median survival times of the two groups were calculated using the Kaplan–Meier estimator. The 6-month and 9-month survival rates in the experimental group were 91.7% and 50%, respectively, while those in the control group were 63.6% and 18.2%, respectively, with significantly statistical difference. The 12-month survival rate in the experimental group was 16.7% and was significantly higher than that in the control group (8.3%) [Figure 5].
Figure 5: Comparison of the overall survival in groups A and B

Click here to view



 > Discussion Top


Early-stage pancreatic cancer is usually clinically silent, and disease only becomes apparent after the tumor invades surrounding tissues or metastasizes to distant organs. Since most of the patients with pancreatic cancer are already in the middle and advanced stages upon initial diagnosis, the ratio of patients who underwent surgical resection is low.[9] Due to short postoperative survival, the quality of life and physical health of patients with pancreatic cancer are often seriously compromised. Our results revealed that 41.67% (5/12) clinical response rate in transcatheter arterial infusion (TAI) group. This is consistent with before report. At present, systemic intravenous chemotherapy with gemcitabine remains the primary treatment option for patients with advanced pancreatic cancer.[10]

Regional arterial infusion is an emerging treatment method in recent years. Aigner et al. showed that the median survival time of patients who underwent regional arterial infusion chemotherapy was substantially higher than that of those who received systemic intravenous chemotherapy.[11] Accordingly, the efficacy of antitumor chemotherapy was directly proportional to both the effective concentration and the duration of drug administration. Regional infusion chemotherapy allows the drug to reach the pancreas first and demonstrate the first-pass effect. Furthermore, the slow local blood flow during arterial infusion chemotherapy creates a hypoxic environment in the tumor, thereby exerting the sensitization effect of chemotherapy while promoting tumor necrosis and death. Compared with conventional intravenous infusion techniques, regional infusion chemotherapy can increase local drug concentration, thereby inhibiting the growth and metastasis of tumor cells.[12] However, its pain relief effect is limited. This is also confirmed in our study. We did not observe significantly decreasement of NRS scores in TAI alone treatment group [Table 3].

Recently, the implantation of radioactive particles into tissues for the treatment of pancreatic cancer has attracted the attention of domestic and international researchers. 125I radioactive particles emit γ-rays that have a strong ability to destroy tumor DNA.[13] In addition, the relatively long half-life of 125I, which is approximately 59.6 days, facilitates the delivery of high-dose and long-term cumulative brachytherapy to the target area while minimizing damage to the surrounding normal tissues.[14] A previous study demonstrated that pancreatic cancer cells exhibited neurotropic properties that led to pain.[15] Lu et al. indicated that, in a group of patients who were irradiated with 125I particles, the growth of pancreatic cancer cells and nerve cells was significantly inhibited, which in turn suppressed pancreatic cancer nerve invasion, relieved pain, and impeded tumor growth.[16] On this basis, our study combined arterial infusion chemotherapy with 125I radioactive particle implantation to explore its clinical efficacy in the treatment of pancreatic cancer. The adoption of radioactive particle implantation to control local lesions cannot only kill tumor tissues, but also block related celiac nerve plexus.[17] Therefore, this technique can provide an effective analgesic effect and substantially alleviate complications caused by local pancreatic tumor compression, thereby improving the patient's quality of life. Combined with sequential arterial infusion chemotherapy to control the local progression and micrometastasis of the tumor, the combined approach can both reduce the incidence of metastasis and increase the sensitivity of tumor tissues to radiation therapy. In this study, we found that combination arterial infusion chemotherapy and I125 seed implantation not only enhance clinical response rate (41.67%–72.73%) but also decrease NRS score in middle to server pain. Notably, overall survival rate was significantly higher in combination group than control group in 6, 9, and 12 month following up. In all, the clinical benefit rate, pain level, and quality of life of patients in the observation group were considerably better than those of patients in the control group, which demonstrated the superior clinical efficacy of 125I particle implantation combined with arterial infusion chemotherapy. Notably, over survival.

Despite multiple deficiencies and a small sample size, this study achieved better treatment outcomes and higher quality of life for some patients with middle- or advanced-stage pancreatic cancer. In addition, patients in the observation group showed a significant improvements in the clinical benefit rate, pain level, and quality of life. At presently, the quality of life of patients with advanced cancer is increasingly important, and thus, this study is of particular clinical significance and provides new ideas for the treatment of pancreatic cancer.


 > Conclusion Top


We conclude that 125I radioactive particle implantation combined with regional arterial perfusion chemotherapy is an effective and comprehensive treatment for advanced pancreatic cancer.

Acknowledgment

This study was supported by National Key R and D Program of China (2019YFB1311300), Science and technology innovation project of Dalian City (No: 2018J12SN063).

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

1.
Vincent A, Herman J, Schulick R, Hruban RH, Goggins M. Pancreatic cancer. Lancet 2011;378:607-20.  Back to cited text no. 1
    
2.
Ryan DP, Hong TS, Bardeesy N. Pancreatic adenocarcinoma. N Engl J Med 2014;371:1039-49.  Back to cited text no. 2
    
3.
Liu F, Tang Y, Sun J, Yuan Z, Li S, Sheng J, et al. Regional intra-arterial vs. systemic chemotherapy for advanced pancreatic cancer: A systematic review and meta-analysis of randomized controlled trials. PLoS One 2012;7:e40847.  Back to cited text no. 3
    
4.
Gai B, Zhang F. Chinese expert consensus on radioactive (125) I seeds interstitial implantation brachytherapy for pancreatic cancer. J Cancer Res Ther 2018;14:1455-62.  Back to cited text no. 4
    
5.
Liu B, Zhou T, Geng J, Zhang F, Wang J, Li Y. Percutaneous computed tomography-guided iodine-125 seeds implantation for unresectable pancreatic cancer. Indian J Cancer 2015;52 Suppl 2:e69-74.  Back to cited text no. 5
    
6.
Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1). Eur J Cancer 2009;45:228-47.  Back to cited text no. 6
    
7.
Burris HA 3rd, Moore MJ, Andersen J, Green MR, Rothenberg ML, Modiano MR, et al. Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: A randomized trial. J Clin Oncol 1997;15:2403-13.  Back to cited text no. 7
    
8.
Aaronson NK, Ahmedzai S, Bergman B, Bullinger M, Cull A, Duez NJ, et al. The European Organization for Research and Treatment of Cancer QLQ-C30: A quality-of-life instrument for use in international clinical trials in oncology. J Natl Cancer Inst 1993;85:365-76.  Back to cited text no. 8
    
9.
Cameron JL, Riall TS, Coleman J, Belcher KA. One thousand consecutive pancreaticoduodenectomies. Ann Surg 2006;244:10-5.  Back to cited text no. 9
    
10.
Neoptolemos JP, Palmer DH, Ghaneh P, Psarelli EE, Valle JW, Halloran CM, et al. Comparison of adjuvant gemcitabine and capecitabine with gemcitabine monotherapy in patients with resected pancreatic cancer (ESPAC-4): A multicentre, open-label, randomised, phase 3 trial. Lancet 2017;389:1011-24.  Back to cited text no. 10
    
11.
Aigner KR, Gailhofer S, Kopp S. Regional versus systemic chemotherapy for advanced pancreatic cancer: A randomized study. Hepatogastroenterology 1998;45:1125-9.  Back to cited text no. 11
    
12.
Qiu B, Zhang X, Tsauo J, Zhao H, Gong T, Li J, et al. Transcatheter arterial infusion for pancreatic cancer: A 10-year National Cancer Center experience in 115 patients and literature review. Abdom Radiol (NY) 2019;44:2801-8.  Back to cited text no. 12
    
13.
Krishnaswamy V. Dose distribution around an 125I seed source in tissue. Radiology 1978;126:489-91.  Back to cited text no. 13
    
14.
Kreth FW, Thon N, Siefert A, Tonn JC. The place of interstitial brachytherapy and radiosurgery for low-grade gliomas. Adv Tech Stand Neurosurg 2010;35:183-212.  Back to cited text no. 14
    
15.
Bapat AA, Hostetter G, Von Hoff DD, Han H. Perineural invasion and associated pain in pancreatic cancer. Nat Rev Cancer 2011;11:695-707.  Back to cited text no. 15
    
16.
Lu Z, Dong TH, Si PR, Shen W, Bi YL, Min M, et al. Continuous low-dose-rate irradiation of iodine-125 seeds inhibiting perineural invasion in pancreatic cancer. Chin Med J (Engl) 2016;129:2460-8.  Back to cited text no. 16
    
17.
Jia SN, Wen FX, Gong TT, Li X, Wang HJ, Sun YM, et al. A review on the efficacy and safety of iodine-125 seed implantation in unresectable pancreatic cancers. Int J Radiat Biol 2020;96:383-9.  Back to cited text no. 17
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
 
  Search
 
Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
Access Statistics
Email Alert *
Add to My List *
* Registration required (free)

  >Abstract>Introduction>Subjects and Methods>Results>Discussion>Conclusion>Article Figures>Article Tables
  In this article
>References

 Article Access Statistics
    Viewed270    
    Printed0    
    Emailed0    
    PDF Downloaded8    
    Comments [Add]    

Recommend this journal


[TAG2]
[TAG3]
[TAG4]