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ORIGINAL ARTICLE
Year : 2019  |  Volume : 15  |  Issue : 7  |  Page : 1567-1573

Preliminary clinical efficacy of iodine-125 seed implantation for the treatment of advanced malignant lung tumors


Department of Interventional Therapy, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing, China

Date of Submission08-Aug-2019
Date of Decision25-Sep-2019
Date of Acceptance09-Oct-2019
Date of Web Publication13-Jan-2020

Correspondence Address:
Dr. Xu Zhu
Department of Interventional Therapy, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_581_19

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 > Abstract 


Aims: This study aims to observe the preliminary clinical efficacy of percutaneous interstitial brachytherapy using iodine-125 seeds for the treatment of advanced malignant lung tumors.
Subjects and Methods: This retrospective study enrolled 24 patients in our hospital with advanced malignant lung tumors between June 2013 and November 2017. Computed tomography (CT)-guided iodine-125 seed implantation therapy was administered to these patients. All patients were followed up at 3, 6, and 12 months after the operation. The clinical efficacy was evaluated by CT.
Results: Among the 24 patients, the objective response rates at 3, 6, and 12 months after the procedure were 50.0%, 50.0%, and 33.3%, respectively. Recent occurrence of adverse reactions were observed, including four cases of pneumothorax, three cases of hemoptysis, and two cases of particle displacement.
Conclusions: CT-guided percutaneous interstitial brachytherapy with iodine-125 seeds can be used for the treatment of lung malignant tumors. Its clinical curative effect is remarkable and it results in limited trauma, reducing the incidence of adverse reactions and improving patient quality of life.

Keywords: Brachytherapy, computed tomography guided, iodine-125 seed, malignant lung tumor


How to cite this article:
Kou F, Gao S, Liu S, Wang X, Chen H, Zhu X, Guo J, Zhang X, Feng A, Liu B. Preliminary clinical efficacy of iodine-125 seed implantation for the treatment of advanced malignant lung tumors. J Can Res Ther 2019;15:1567-73

How to cite this URL:
Kou F, Gao S, Liu S, Wang X, Chen H, Zhu X, Guo J, Zhang X, Feng A, Liu B. Preliminary clinical efficacy of iodine-125 seed implantation for the treatment of advanced malignant lung tumors. J Can Res Ther [serial online] 2019 [cited 2020 Apr 5];15:1567-73. Available from: http://www.cancerjournal.net/text.asp?2019/15/7/1567/275561




 > Introduction Top


Malignant tumors are the second leading cause of death in China. Malignant lung tumors are among the most common malignant tumors, with high incidence rates. The incidence and mortality of primary lung cancer are the highest among malignant tumors worldwide.[1] When diagnosed, the disease has generally progressed to the middle and late stages; thus, patients have lost the chance for radical surgery and have a poor prognosis. At the same time, the lung is a common site for tumor metastasis. More than 60% of malignant tumors have distant metastasis at the first visit, 30%–50% of which metastasize to the lungs. The most common primary tumors include thyroid cancer, breast cancer, kidney cancer, choriocarcinoma, osteosarcoma, liver cancer, stomach cancer, colorectal cancer, and prostate cancer. Conventional treatment includes surgery, chemotherapy, radiation therapy, and targeted therapy. In recent years, therapeutic methods have been increasing, and the implantation of radioactive particles as a form of brachytherapy has been widely performed in clinical practice. Studies have demonstrated the advantages of this treatment, including its safety, effectiveness, reduced complications, and reproducibility.[2],[3],[4],[5] This method has been applied to a variety of solid tumors, including liver cancer, pancreatic cancer, reproductive system tumors, and brain tumors.[6],[7],[8],[9],[10] It also achieves better results in the treatment of malignant lung tumors.[11],[12],[13],[14],[15],[16],[17],[18],[19] This article retrospectively analyzed the clinical data and evaluated the preliminary efficacy of iodine-125 seed implantation in patients with lung malignancy. The report is as follows.


 > Subjects and Methods Top


Patients

The individuals included 24 patients with advanced lung malignancies treated in our hospital between June 2013 and November 2017 who provided written informed consent. The cases included 19 with primary lung cancer and five with lung metastases. There were 19 men and 5 women with an age range of 46–79 years and average age of 67.6 ± 12.0 years. The tumor size ranged from 20 to 81 mm with an average of 38.9 ± 14.0 mm. Among primary lung cancer cases, 13 were squamous cell carcinoma (SCC), two were adenocarcinoma, two were adenosquamous carcinoma, one was small cell lung cancer, and one was atypical carcinoid; 12 cases were central type and seven were peripheral type. All cases were Stage IIIA and above. The lung metastases included three cases of hepatocellular carcinoma (HCC) and two cases of colon cancer, all of which were Stage IV [Table 1] and [Table 2].
Table 1: Clinical features of the patients

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Table 2: Detailed characteristics of the 24 patients

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Instrumentation

Iodine-125 seed implantation was guided by a Siemens Miyabi Angio-computed tomography (CT) scanner (64-slice) and a Siemens Symbia T16 Single photon emission CT/CT with an interval of 5 mm. Chest CT was performed for all patients to evaluate the tumor characteristics 2 weeks before the procedure. A treatment planning system (TPS; KL-SIRPS-3D of Beijing Tianhang Kelin Technology Development Co., Ltd.) was used to calculate the number and distribution of seeds based on the preoperative CT images. The TPS ensured a prescription dose of 145 Gy to the target volume. The implantation needle (18 G), turnable implantation gun, and iodine-125 seeds were all provided by Beijing ZHIBO Hi-Tech Biotechnology Co., Ltd. The diameter of each seed was 0.8 mm, and the length was 4.5 mm. The halflife of each seed was 59.6 days, and the tissuepenetration distance was 1.7 cm. The activity of each iodine-125 seed was 0.5–0.8 mCi.

Procedure

Before the procedure, all patients were scanned by 5-mm thin slice chest CT to measure the tumor volume. The CT scan images were transferred to TPS. The matched peripheral dose was calculated based on the target volume and iodine-125 seed activity, the position of the implantation needle, and the number of seeds. The implantation procedure was performed under local anesthesia (2% lidocaine) in the CT room. The implantation needle was inserted into the tumor tissue under CT guidance while avoiding puncturing the nearby vessels and other organs. The seeds were then implanted using a turntable implantation gun, with a center-to-center space between seeds of 0.5–1.0 cm. After the procedure, the entire lung was scanned routinely to observe seed distribution and to assess complications such as pneumothorax and bleeding. The patients were kept in the interventional ward for 1–2 days after the procedure.

Follow-up and efficacy evaluation

Each patient underwent follow-up examinations at 3, 6, and 12 months after the procedure. Chest CT was performed at each follow-up. The physical status of the patients and the tumor diameters were recorded during the follow-up period. Solid tumor efficacy evaluation criteria (RECIST 1.1) were used to assess the therapeutic efficacy.

Complete response (CR) was defined as the complete disappearance of a lesion for >4 weeks. Partial response (PR) was defined as a decrease in lesion by ≥30% that then remained unchanged for 4 weeks. Stable disease (SD) was defined as a decrease in tumor size by <30% or increase by <20%. Progressive disease (PD) defined as an increase in lesion size by ≥20%. The local tumor objective response rate (ORR) was defined as the sum of CR and PR, and the disease control rate (DCR) was defined as the absence of tumor progression (CR and PR and SD).


 > Results Top


All patients tolerated the brachytherapy well with no operation-related deaths. Three months after the procedure, three cases (12.5%) achieved a CR, nine cases (37.5%) achieved a PR, 12 cases (50.0%) had SD, and there was no PD, resulting in an ORR of 50.0% and DCR of 100%. The 6- and 12-month ORRs were 50.0% and 91.7%, respectively, while the DCRs were 33.3% and 75.0%, respectively [Table 3].
Table 3: Evaluation of the clinical efficacy after iodine-125 seed implantation

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Complications

Among all cases, after brachytherapy, three patients experienced hemoptysis, which was relieved after hemostasis treatment; four patients developed pneumothorax, three of which had a minor pneumothorax and one had a massive pneumothorax, which improved after 1 week of closed thoracic drainage; and two cases experienced seed shifting.

Typical cases

A 49-year-old male with HCC and metastasis in the right lower lung showed CR to brachytherapy [Figure 1]. Iodine-125 seeds were implanted in his right lower lung tumor region for brachytherapy. The right lower lung tumor had completely disappeared at 3, 6, and 12 months after the procedure.
Figure 1: (a) Computed tomography image showing a metastatic tumor in the right lower lung. (b) Computed tomography image 3 months after iodine-125 seed implantation. (c) Computed tomography image 6 months after the procedure. (d) Computed tomography image 12 months after the procedure

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A 78-year-old male with moderately differentiated squamous cell lung carcinoma in his left lower lung and progression after chemotherapy and radiotherapy showed a significant reduction in tumor size after iodine-125 seed implantation [Figure 2].
Figure 2: (a) Computed tomography image showing moderately differentiated squamous cell carcinoma in the left lower lung. (b) Computed tomography image 3 months after iodine-125 seed implantation. (c) Computed tomography image 6 months after the procedure. (d) Computed tomography image 12 months after the procedure. (e) Dose-volume histogram calculated for treatment planning. (f and g) Postoperative verification images

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A 73-year-old woman with a poorly differentiated adenosquamous carcinoma in her right lung that had progressed after multicourse treatment showed a significant reduction in tumor size after iodine-125 seed implantation [Figure 3].
Figure 3: (a) Computed tomography image showing a poorly differentiated adenosquamous carcinoma in the right lung. (b) Computed tomography image 3 months after iodine-125 seed implantation. (c) Dose-volume histogram calculated for treatment planning. (d and e) Postoperative verification images

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A 77-year-old male with a moderately differentiated squamous cell lung carcinoma in his right lung and progression after chemotherapy and radiotherapy showed a significant reduction in tumor size after iodine-125 seed implantation [Figure 4].
Figure 4: (a) Computed tomography image showing moderately differentiated squamous cell carcinoma in the right lung. (b) Computed tomography image 3 months after iodine-125 seed implantation. (c) Computed tomography image 6 months after the procedure. (d) Computed tomography image 12 months after the procedure. (e) Dose-volume histogram calculated for treatment planning. (f and g) Postoperative verification images

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A 74-year-old male with local recurrence after surgery for moderately differentiated SCC in his right lower lung exhibited a significant reduction in tumor size after iodine-125 seed implantation [Figure 5].
Figure 5: (a) Computed tomography image showing local recurrence after surgery for moderately differentiated squamous cell carcinoma in the right lower lung. (b) Computed tomography image 3 months after iodine-125 seed implantation. (c) Dose-volume histogram calculated for treatment planning. (d and e) Postoperative verification images

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 > Discussion Top


CT-guided iodine-125 seed implantation is a minimally invasive treatment and form of interstitial brachytherapy. Iodine-125 is a low-energy radionuclide that continuously releases radiation and emits X-rays and gamma rays of 27.4–31.5 keV. It can kill tumor cells by continuously destroying the DNA double strands and making them lose their proliferative ability.[20] The radiation directly acts on the tumor tissue, and its physical half-life is 59.6 days. The effective continuous irradiation period for the tumor is up to 200 days, which increases the effect of radiotherapy. Meanwhile, the radiation penetration is extremely weak: as short as 17 mm. Therefore, the damage to the surrounding normal tissue is minimal. This treatment method results in a significant reduction in tumor reproliferation due to continuous irradiation; the continuous low-dose irradiation inhibits mitosis of the tumor cells arresting them in the G2 phase. Therefore, the treatment can maximally inactivate tumor cells to achieve the therapeutic purpose.[21]

Studies have shown that interstitial brachytherapy using iodine-125 seeds can provide good results in the treatment of malignant lung tumors.[21] In our study, 24 patients had satisfactory results with an ORR of 50.0% and a DCR of 100% at 3 months postoperatively; 50.0% ORR and 91.7% DCR at 6 months postoperatively; and 33.3% ORR and 75.0% DCR at 12 months postoperatively. Most of the patients in this group had progressed after systemic chemotherapy and radiotherapy. The tumor cells were dormant or resistant to various chemotherapeutic drugs. They were not sensitive to chemotherapy. The radioactive seeds can kill tumor cells in large numbers and damage active cells within the implanted range. The treatment may also increase the sensitivity of active tumor cells to chemotherapeutic drugs due to the reduced tumor burden, which is conducive to further comprehensive treatment of cancer patients. In addition, the efficacy of radiotherapy for lung metastases is closely related to whether the primary tumor is sensitive to radiation.[22]

In this group of patients, four developed pneumothorax, including one case of massive pneumothorax, which was remitted after thoracic drainage closure; three patients developed hemoptysis and received hemostasis treatment; and two patients showed particle displacement without obvious discomfort.

The preliminary results were satisfactory. Compared to other treatment methods, the method described in the present study can improve patient quality of life and has good value for clinical application. However, the indications should be strictly controlled, the characteristics of chest anatomy and imaging should be mastered, and CT positioning should be skillfully applied. Moreover, the preoperative preparation should be sufficient, and the procedure should be performed according to the preoperative plan. Finally, complications should be diagnosed and treated promptly.

Our study has several limitations, including the limited number of patients and lack of assessment of long-term clinical efficacy. Therefore, large-scale studies with long-term follow-up periods are needed to confirm the clinical efficacy of this method.


 > Conclusions Top


CT-guided percutaneous interstitial brachytherapy using iodine-125 seeds for the treatment of malignant lung tumors is safe and effective, has few side effects, and can be repeated.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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    Figures

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

  [Table 1], [Table 2], [Table 3]



 

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