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 »  Abstract
 » Introduction
 »  Materials and Me...
 » Results
 » Discussion
 » Conclusion
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  Table of Contents  
ORIGINAL ARTICLE
Year : 2015  |  Volume : 52  |  Issue : 6  |  Page : 69-74
 

Percutaneous computed tomography-guided iodine-125 seeds implantation for unresectable pancreatic cancer


1 Department of Interventional Medicine, The Second Hospital of Shandong University, Jinan, Shandong Province, PR of, China
2 Postgraduate student of Medical College, Shandong University, Jinan, PR of, China
3 Department of Hepatobiliary Surgery, Weihai Municipal Hospital, Shandong Province, Jinan, PR of, China
4 Department of Medical Imaging and Interventional Radiology, Cancer Center and State Key Laboratory of Oncology in South , Sun Yat-sen University, Guangzhou, Guangdong, PR of, China
5 Department of Radiation Oncology, Cancer Centre, Peking University Third Hospital, Beijing, PR of, China
6 Department of Interventional Medicine, The Second Hospital of Shandong University, Shandong, Shandong Province, PR of, China

Date of Web Publication24-Dec-2015

Correspondence Address:
Y Li
Department of Interventional Medicine, The Second Hospital of Shandong University, Jinan, Shandong Province
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.172517

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 » Abstract 

Background: To examine the safety and clinical efficacy of computed tomography (CT)-guided radioactive iodine-125 (125I) seeds implantation for patients with unresectable pancreatic cancer. Materials and Methods: A group of 26 patients with pathologically confirmed unresectable pancreatic cancer underwent percutaneous CT-guided 125I seeds implantation. Part of them received transarterial chemotherapy and/or percutaneous transhepatic cholangial drainage before or after seeds implantation. The primary endpoints were the objective response rates, local control rates, and overall survival. Results: CT scan 2 months after treatment revealed complete response (CR) in 8 patients, partial response (PR) in 9 patients. Overall response rate (CR + PR) is 65.38%. Local control rate was 88.46%. Median survival of the whole group was 15.3 months, whereas for Stage III and IV was 17.6 and 9.1 months, respectively. The estimated 1-year survival was 30.77%. Conclusions: We consider CT-guided 125I seeds implantation as a safe, effective, uncomplicated treatment for unresectable pancreatic cancer.


Keywords: Brachytherapy, iodine, pancreas cancer, radioisotopes


How to cite this article:
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 S2:69-74

How to cite this URL:
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 [serial online] 2015 [cited 2019 Aug 19];52, Suppl S2:69-74. Available from: http://www.indianjcancer.com/text.asp?2015/52/6/69/172517



 » Introduction Top


Pancreas carcinoma is known as a devastating tumor. Despite the introduction of multiple new methods and combined modalities, the prognosis remains very poor. Extensive resection of advanced pancreas cancer is associated with significant morbidity and mortality. External beam radiation therapy (EBRT) and chemotherapy are usually regarded as insensitive to pancreatic cancer and associated with more systemic side effects, although EBRT can relieve pain in up to 50–85% of patients.[1]

In China, age-standardized 5-year relative survival of pancreas cancer is only 11.7%.[2]

Radioactive iodine-125 (125 I) seed implantation is a relative new option for cancer, which has been proved to be effective in prostate cancer,[3] recurrent rectal cancer,[4] liver cancer, lung cancer, and soft tissue sarcoma,[5] which is characterized by its minimal trauma and fewer complications. In recent 6 years, we elaborate 125 I seed implantation in unresectable pancreatic cancer (Stage III and IV). In this research, we investigate the feasibility and efficacy of computed tomography (CT)-guided implantation of 125 I seeds as an alternative management of advanced pancreas cancer which cannot be treated surgical resection.


 » Materials and Methods Top


From December 2010 to May 2015, a total of 26 patients with unresectable pancreatic cancer (Stage III and IV) ranging in age from 48 to 86 underwent CT-guided 125 I seeds implantation at The Second Hospital of Shandong University. The characteristics of patients are reviewed in [Table 1]. Prior to CT-guided seeds implantation, patients had undergone the treatment protocol: One patient received biliary-enteric anastomosis; one received pancreatic tail resection and splenectomy combined with adjuvant chemotherapy with gemcitabine and oxaliplatin; one received percutaneous transhepatic cholangial drainage (PTCD) and bile duct stent; one received transarterial chemotherapy with gemcitabine and oxaliplatin [Table 2]. Nine patients suffered from severe pain (Numerical Rating Scale, [NRS] 7–9), six suffered from moderate dorsalgia and abdominal pain (NRS, 4–6), and other patients complained no pain.
Table 1: Patients and primary tumor characteristics (n=26)

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Table 2: Patients characteristics before seeds implantation

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Treatment planning

One week before 125 I seeds implantation, CT scans with a 5 mm thickness slice in a prone position were performed to get a detailed tumor volume study for all patients. Transverse images of the pancreas tumor were obtained at 5 mm intervals. The radiation oncologist outlined the gross tumor volume (GTV) and areas at risk for the subclinical disease on each transverse image. The planning treatment volume (PTV) include the entire GTV and 1.0 margin [Figure 1]. The dose was prescribed as the minimal peripheral dose (MPD) encompassing the PTV. The distribution and dose of 125 I seeds were calculated using computerized treatment planning system (TPS) [Figure 2].
Figure 1: (a) Outlined planning treatment volume. (b) Treatment planning system curve about the distribution and dose of iodine-125 seeds

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Figure 2: (a) Needles inserted according to treatment planning system plan. (b) Seeds were implanted into the lesion

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Seed implantation technique

Liquid diet 1 day and enteroclysis 12 h before the procedure is necessary. All patients received gastric tube placement and general intravenous anesthesia with propofol and dexmedetomidine. The procedure took 60–100 min in CT room. Eighteen gauge needles were inserted according to TPS plan and extended at least 0.5–1.0 cm beyond GTV [Figure 3]. The half value of 1.7 cm in tissue 125 I seeds (Jaco pharmaceuticals Co., Ltd., Ningbo, China, half-life: 59.6 days, energy levels 27.4–31.4 KeV) gave a characteristic sharp dose drop-off and allowed for safe handling. Seeds were implanted with a space at equal distance, usually 0.5–1.0 cm center-to-center. The number of seeds implanted ranged from 30 to 80, with a median of 53. Specific activity of the seeds ranged from 0.6 to 0.8 mCi. The MPD of 125 I seeds was 110–130 Gy (median 115 Gy).
Figure 3: Overall survival of the whole group

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Postimplant treatment

One patient received PTCD/bile duct stent. Six patients received transarterial chemotherapy with gemcitabine and oxaliplatin for 1–4 cycles. Two patients received PTCD/bile duct stent and transarterial chemotherapy with gemcitabine and oxaliplatin for 1–3 cycles. Four patients received transcatheter arterial chemoembolization and transarterial chemotherapy with gemcitabine and oxaliplatin for 1–3 cycles. One patient received neurolytic celiac plexus block with dehydrated alcohol to release severe dorsalgia and abdominal pain. The treatment characteristics and outcomes are summarized in [Table 3].
Table 3: Patients characteristics of radioactive seed implantation and outcome

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Complication

At each follow-up visit, all patients were interviewed regarding clinical manifestation of pancreatitis, cholangiolitis, upper gastrointestinal bleeding or perforation, pancreatitis, pancreatic fistula, and radiation enteritis. Their complaints were documented with a modified Radiation Therapy Oncology Group scoring scale.[6]

Follow-up

The median follow-up was 13.7 months (3–22 months). Patients were monitored by an interventional radiologist and radiation oncologists. Enhanced CT or magnetic resonance imaging of upper abdomen, chest X-ray, or CT were performed every 2–3 months. Tumor responses were accessed with Response evaluation criteria in solid tumors version 1.1 published in 2009.[7] Pain intensity was evaluated and grated by Adult Cancer Pain Clinical Practice Guideline.[8] NRS 1–3 is mild, 4–6 is moderate, 7–10 is severe. Overall, the pain relief response rate (RR) was defined as the sum of the complete response (CR) and partial response (PR) patients.

Statistical analysis

The follow-up time was calculated from the date of seed implantation. Survival and locoregional failure estimates were calculated according to the actuarial method of Kaplan and Meier. The primary endpoints of this study were the objective response rates, toxicities, time to progression, local control rates, and overall survival. For calculation of survival, deaths from any cause were scored as events. Local control was defined as lack of tumor progression either in or adjacent to the implanted volume.


 » Results Top


Pain relief

Among nine patients (19.2%) with severe pain before treatment, three complained mild pain (NRS 1–3) following implantation, and two had moderate pain with an NRS of 4–6. In four patients, moderate pain prior to implantation became mild pain. Another two patients with moderate pain showed no change after treatment. The pain relief RR was 69.24% (9/13). The pain-free survival was 0–15 months with a median of 11 months.

Response to treatment

CT scan 2 months after treatment revealed CR in 8 patients, PR in 9 patients, stable disease in 6 patients, and progressive disease in 3 patients. Overall response rate (CR + PR) is 65.38%. Local control rate was 88.46%.

Overall survival

The follow-up period was 3–22 months. The median survival of the whole group was 15.3 months, whereas for Stage III and IV was 17.6 and 9.1 months, respectively. The estimated 1-year survival was 30.77% [Figure 3]. The median survival for pure seeds implantation is 10.7 months [Figure 4]. There is no significant difference between the seeds group and seeds–drug/PTCD combined group in terms of the median survival time.
Figure 4: Survival of pure seeds implantation and seeds-drug/percutaneous transhepatic cholangial drainage

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Complications

Seven patients showed fever (low than 38.5°C) in 3–5 days after seed implantation, which was considered normal as absorption fever. Fever higher than 39.0°C, upper gastrointestinal bleeding or perforation, pancreatitis, pancreatic fistula, radiation enteritis, or cholangiolitis appeared in no patient. Five patients who received transarterial chemotherapy showed leukopenia, which was reversed with medicine, including vitamin B4 and/or Recombinant Human Interleukin-11 for Injection.


 » Discussion Top


Pancreatic carcinoma is one of the most deadly cancers and it occurs as the fifth and sixth most common causes of cancer-related death in men and women, respectively.[9] It is difficult to diagnose at its early stage because of its lack of imaging findings and typical clinical manifestations. Hence, when diagnosed, patients are in late stage with abdominal pain, abdominal distension, progressive jaundice, etc., Whipple procedure, also known as Pancreaticoduodenectomy, is still the first choice for the treatment of pancreatic carcinoma, if it is resectable.[10] People always consider surgery as the best treatment for malignant tumor. However, the indication for surgery is very strict and its incidence of postoperative complications, such as longer operative time, bleeding, lower albumin, long periods to bowel movement and normal diet, is very high. Besides, in end-stage of the tumor, Stage III and IV, older patients with poor healthy are also not suitable for surgery operation.

Intravenous chemotherapy with gemcitabine is a traditional treatment for local control of advanced or metastatic pancreatic cancer. However, local recurrence and progression in the pancreas and peripancreatic lymph nodes after this treatment has been reported to be as high as 58%.[11] Moreover, as mentioned in the introduction, EBRT is usually regarded as insensitive to pancreatic cancer and associated with more systemic side effects.

Radioactive 125 I seed implantation, the interstitial irradiation, is a new kind of treatment for malignant tumor. Based on the TPS, percutaneous CT-guided 125 I seed implantation seeds can make continuous and short distance radiation, which makes tumor tissue receive the greatest degree of damage, and normal organization is not or within minor damage. Patients for whom surgery is not appropriate or who refuse surgery,125 I seed implantation is a good option, with regarding interference-free and accurately predictable energy distribution, treatable size of a target lesion, and a lower rate of acute adverse effects possible by maintaining tissue continuity. In recent years, this technique has been applied in prostate cancer, primary and metastatic lung cancer, breast cancer, brain tumors, pancreatic cancer, primary and metastatic liver cancer, and soft tissue sarcoma.[12],[13],[14] However, there are few reports on CT-guided radioactive seeds implantation for pancreatic cancer.

Our data suggest that local control rates can be enhanced by the addition of transarterial chemotherapy and/or PTCD. Despite lacking definitive proof, positive results allow us to continue the use of seeds-drug/PTCD combination therapy. For patients with the first symptom of jaundice, PTCD/bile duct stent will be implied to recover the patency of bile duct and protect liver function, which helps subsequent therapy. Cron et al.[15] suggested that the best time for intravenous chemotherapy is within 3–4 days after implantation of 125 I seeds because the permeability of the surrounding vasculature is promoted by the radiation effects of the seeds at that time. In this group of patients, time of transarterial chemotherapy was uncertain, before or after the seeds implantation. The interval between transarterial chemotherapy and seeds implantation was about 1 week. The median survival time for pure seeds implantation and seeds-drug/PTCD combined therapy was 10.7 months and 15.3 months, respectively; it does not reach statistically significant but also encouraged our further evaluation.

In this group of patients, we implanted 125 I seeds under CT guidance and yielded good local control of the disease. We obtained even distribution of the radioactive seeds with overall response rate of 65.38%, local control rate of 88.46%, and pain relief rate of 69.24%. Nevertheless, there were fewer complications compared with other interventional ablation procedures. From these data, it appeared that 125 I implantation of unresectable pancreatic tumors offered high control of the primary tumor and significant palliation of symptoms. After promising results, we will further evaluate interventional brachytherapy as an additional tool in multimodal oncologic therapy concepts.


 » Conclusion Top


This study suggested that CT-guided 125 I seeds implantation appeared to be safe, effective, uncomplicated, and could produce adequate pain relief for unresectable pancreatic cancer.

 
 » References Top

1.
Minsky BD, Hilaris B, Fuks Z. The role of radiation therapy in the control of pain from pancreatic carcinoma. J Pain Symptom Manage 1988;3:199-205.  Back to cited text no. 1
    
2.
Zeng H, Zheng R, Guo Y, Zhang S, Zou X, Wang N, et al. Cancer survival in China, 2003-2005: A population-based study. Int J Cancer 2015;136:1921-30.  Back to cited text no. 2
    
3.
Ebara S, Katayama N, Tanimoto R, Edamura K, Nose H, Manabe D, et al. Iodine-125 seed implantation (permanent brachytherapy) for clinically localized prostate cancer. Acta Med Okayama 2008;62:9-13.  Back to cited text no. 3
    
4.
Wang JJ, Yuan HS, Li JN, Jiang YL, Tian SQ, Yang RJ. CT-guided radioactive seed implantation for recurrent rectal carcinoma after multiple therapy. Med Oncol 2010;27:421-9.  Back to cited text no. 4
    
5.
Li Y, Wang Y, Liu B, Li Z, Wang W.125 I brachytherapy seeds implantation for inoperable low-grade leiomyosarcoma of inferior vena cava. Korean J Radiol 2013;14:278-82.  Back to cited text no. 5
    
6.
Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC). Int J Radiat Oncol Biol Phys 1995;31:1341-6.  Back to cited text no. 6
    
7.
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. 7
    
8.
Classification of chronic pain. Descriptions of chronic pain syndromes and definitions of pain terms. Prepared by the international association for the study of pain, subcommittee on taxonomy. Pain Suppl 1986;3:S1-226.  Back to cited text no. 8
    
9.
Zou YP, Li WM, Zheng F, Li FC, Huang H, Du JD, et al. Intraoperative radiofrequency ablation combined with 125 iodine seed implantation for unresectable pancreatic cancer. World J Gastroenterol 2010;16:5104-10.  Back to cited text no. 9
    
10.
Michalski CW, Weitz J, Büchler MW. Surgery insight: Surgical management of pancreatic cancer. Nat Clin Pract Oncol 2007;4:526-35.  Back to cited text no. 10
    
11.
Xie DR, Liang HL, Wang Y, Guo SS, Yang Q. Meta-analysis on inoperable pancreatic cancer: A comparison between gemcitabine-based combination therapy and gemcitabine alone. World J Gastroenterol 2006;12:6973-81.  Back to cited text no. 11
    
12.
Peretz T, Nori D, Hilaris B, Manolatos S, Linares L, Harrison L, et al. Treatment of primary unresectable carcinoma of the pancreas with I-125 implantation. Int J Radiat Oncol Biol Phys 1989;17:931-5.  Back to cited text no. 12
    
13.
Zelefsky MJ, Hollister T, Raben A, Matthews S, Wallner KE. Five-year biochemical outcome and toxicity with transperineal CT-planned permanent I-125 prostate implantation for patients with localized prostate cancer. Int J Radiat Oncol Biol Phys 2000;47:1261-6.  Back to cited text no. 13
    
14.
Afsharpour H, D'Amours M, Coté B, Carrier JF, Verhaegen F, Beaulieu L. A Monte Carlo study on the effect of seed design on the interseed attenuation in permanent prostate implants. Med Phys 2008;35:3671-81.  Back to cited text no. 14
    
15.
Cron GO, Beghein N, Crokart N, Chavée E, Bernard S, Vynckier S, et al. Changes in the tumor microenvironment during low-dose-rate permanent seed implantation iodine-125 brachytherapy. Int J Radiat Oncol Biol Phys 2005;63:1245-51.  Back to cited text no. 15
    


    Figures

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

  [Table 1], [Table 2], [Table 3]



 

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