|Year : 2014 | Volume
| Issue : 6 | Page : 9-12
Computed tomography-guided iodine-125 interstitial implantation as an alternative treatment option for lung cancer
G Jiang1, Z Li1, A Ding2, F Zhou3, W Jiao4, D Tang4, W Qiu2, L Yue2, W Xu1
1 Department of Radiology, Affiliated Hospital of Qingdao University, Qingdao, China
2 Department of Interventional Radiology, Affiliated Hospital of Qingdao University, Qingdao, China
3 Department of Radiotherapy, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, China
4 Department of Oncology and Thoracic Surgery, Affiliated Hospital of Qingdao University, Qingdao, China
|Date of Web Publication||24-Feb-2015|
Department of Radiology, Affiliated Hospital of Qingdao University, Qingdao
Source of Support: This study is supported by Shandong Tackle Key Problems in Science and Technology (2010GSF10245), Conflict of Interest: None
Purpose: The aim was to evaluate the safety, feasibility and efficacy of computed tomography (CT)-guided percutaneous interstitial brachytherapy using radioactive iodine-125 ( 125 I) seeds for the treatment of lung cancer. Materials and Methods: Included in this study were 45 male and 35 female patients aged 52-85 years (mean 72-year) who were diagnosed with lung cancer. Of the 80 cases of lung cancer, 38 were pathologically confirmed as squamous cell carcinoma, 29 as adenocarcinoma, 2 as small cell lung cancer, and 11 as metastatic lung cancer. Percutaneous interstitial implantation of radioactive 125 I seeds was performed under CT guidance. The treatment planning system was used to reconstruct three-dimensional images of the tumor to determine the quantity and distribution of 125 I seeds to be implanted. Under CT guidance, 125 I seeds were embedded into the tumor, with the matched peripheral dose set at 100-130 Gy. Follow-up CT scan was done in 2-month to explore the treatment efficacy. Results: The procedure was successful in all patients. No major procedure-associated death occurred. The duration of follow-up was 6-month. Complete response (CR) was seen in 38 cases (47.5%), partial response (PR) in 27 cases (33.75%), stable disease (SD) in 10 cases (12.5%), and progressive disease in 5 cases (6.25%), with a local control rate (CR + PR + SD) of 93.75%. The 2-, 4- and 6-month overall response rate (CR + PR) was 78%, 83% and 81%, respectively. Conclusion: Implantation of CT-guided 125 I seeds is a safe and effective alternative option for the treatment of lung cancer.
Keywords: Brachytherapy, computed tomography, iodine-125, lung neoplasm
|How to cite this article:|
Jiang G, Li Z, Ding A, Zhou F, Jiao W, Tang D, Qiu W, Yue L, Xu W. Computed tomography-guided iodine-125 interstitial implantation as an alternative treatment option for lung cancer. Indian J Cancer 2014;51, Suppl S2:9-12
|How to cite this URL:|
Jiang G, Li Z, Ding A, Zhou F, Jiao W, Tang D, Qiu W, Yue L, Xu W. Computed tomography-guided iodine-125 interstitial implantation as an alternative treatment option for lung cancer. Indian J Cancer [serial online] 2014 [cited 2022 Dec 3];51, Suppl S2:9-12. Available from: https://www.indianjcancer.com/text.asp?2014/51/6/9/151999
| » Introduction|| |
The curative effect of lung cancer mainly depends on the possibility of complete resection.  However, this is often not possible for many patients either because of inadequate lung function or because of local or distant metastasis of the disease. , Although surgical treatment combined with external radiotherapy and/or chemotherapy is recommended, the therapeutic efficacy remains unsatisfactory. Therefore, other treatment options should be explored. Three-dimensional stereotactic radiotherapy using interstitial implantation of iodine-125 ( 125 I) seeds is considered a novel complement to surgery and external radiotherapy.  Interstitial prostate brachytherapy using permanently implanted inert seeds containing radioactive sources has been reported to treat prostate cancer. This approach has been used both as the primary form of therapy for localized disease and a local boost combined with external radiotherapy.
With the current use of neoadjuvant therapy and more aggressive surgical intervention as well as the recent initiation of the American College of Surgeons Oncology Group Phase III trial comparing sublobar resection with or without brachytherapy in early-stage high-risk patients, the possibility of intervening brachytherapy has significantly increased in these institutions. Based on these developing issues, brachytherapy seems to become the hotspot in the management of operable lung cancers.
Brachytherapy has undergone a long history of usage and has been recognized as a safe and effective method to provide for high-dose permanent irradiation, but there is not enough evidence to confirm the feasibility and efficacy of percutaneous interstitial brachytherapy (PIBT) in treating lung cancer. Although some recent studies reported that PIBT was safe and effective in the treatment of Stage I none small-cell lung cancer (NSCLC) with virtually no increased morbidity, there is a lack of sufficient data to support their conclusions.
At present, there have been no correlated reports about radioactive seed implant brachytherapy for lung cancers after multiple therapeutic modalities. The aim of the present study was to evaluate the feasibility and efficacy of computed tomography (CT)-guided implantation of 125 I seeds by reviewing 80 lung cancer patients who received interstitial brachytherapy of 125 I seeds, and see whether it could be used as an alternative option for the management of lung cancer after other multiple treatments.
| » Materials and Methods|| |
Source of specimens
Eighty patients with lung cancer were enrolled from October 2008 to October 2012. The mean age of the patients was 72-year (range, 52-85 years). The patients were followed-up for 6-month. Of the 80 patients, 45 (56.25%) were male and 35 (43.75%) were female. The diagnosis of all cases was confirmed by fine-needle aspiration biopsy or bronchoscopic pathology. Patients would undergo 125 I seed implantation unless the tumor were removed by surgery. Five patients refused surgery because of their poor general conditions or other reasons. Of the 80 patients, 69 patients had primary tumors and 11 patients had metastatic tumors. Of them, 62 patients had received different therapies including surgical resection, chemotherapy, external radiotherapy or comprehensive treatment. The clinical characteristics of these patients are listed in [Table 1]. TNM stage of the tumors was assessed according to the 7 th edition of TNM Classification of Malignant Tumors,  including stage Ib in one patient (1.25%); IIa in 4 patients (5%); IIb in 7 patients (8.75%); IIIa in 9 patients (11.25%); IIIb in 22 patients (27.5%); and IV in 37 patients (46.25%).
All sections were reviewed by a pathologist to confirm the malignancy. The research protocol was approved by the Ethics Committee of the Affiliated Hospital of Qingdao University School of Medicine, and informed consent was obtained from all patients.
Implantation of radioactive 125 I seeds was guided by GE light speed 16-slice helical CT (GE, Connecticut, US) with an interval of 1.25 mm. Chest CT scan was performed for all patients to obtain information about tumor characters 1-2 weeks before brachytherapy. A treatment planning system (TPS; 76633QD, Beijing, China) was applied to calculate the number and distribution of the seeds based on preoperative CT images. The TPS ensured a minimal peripheral dose of 144 Gy to the target volume. The implantation needle, turnable implantation gun and 125 I seeds were all provided by Beijing ZHIBO Bio-Medical Technology Co., Ltd., (Beijing, China). The diameter of each seed was 0.8-4.5 mm. The half-life of each seed was 59.6 days, the mean energy was 27-35 keV, and the tissue-penetration distance was 1.7 cm. The activity of 125 I seeds was 0.6-0.8 mCi.
All patients were scanned with 10-mm thin slices to measure the volume of the tumors before the procedure. Three-dimensional reconstruction was performed, and the CT scan images were transferred to a radiotherapy planning system. The matched peripheral dose was calculated on the basis of the target volume and activity of 125 I seeds, the position of the implantation needle, and the number of the seeds. The implantation procedure was undertaken under local anesthesia (2% lidocaine) in the CT Suite. The implantation needle was inserted into the tumor tissue under CT guidance. Seeds were then implanted, with the center-to-center space between seeds kept at 1.0 cm. After the procedure, the entire lung was imaged routinely to assess complications such as pneumothorax and bleeding [Figure 1].
|Figure 1: Computed tomography (CT) images of a 73-year-old male patient with squamous cell carcinoma. (a) A mass involved the descending aorta (white arrow). (b) The implantation needles were fan-shaped due to occlusion of the ribs and thoracic vertebrae. (c) 125I seeds were inserted into the tumor tissue under CT guidance. (d) 125I seeds were placed in the mass according to CT scan and no pneumothorax was observed after implantation|
Click here to view
The follow-up duration was 6-month. CT was carried out every 2-month in all patients or earlier if new clinical symptoms appeared. The physical status of the patients and the diameter of the tumors were recorded during the follow-up period. The response evaluation criteria in solid tumors were used to assess the therapeutic effect.
SPSS version 17.0 (SPSS, Chicago, IL, USA) was used for statistical analysis. Data are expressed as mean ± standard deviation overall local control was calculated according to the actuarial method of Kaplan and Meier.
| » Results|| |
All patients tolerated the brachytherapy well with no operation-related death occurring. One patient died of brain metastasis in the 2 nd month after surgery, and was considered a cancer-related death. In addition, two patients died of multiple organ failure in the 6 th month after surgery. No local failure was observed during the 6-month follow-up period. [Figure 2] shows the therapeutic effect of a 73-year-old patient. Complete response (CR) was achieved in 38 cases (47.5%), partial response (PR) in 27 cases (33.75%), stable disease (SD) in 10 cases (12.5%), and progressive disease in 5 cases (6.25%), with a local control rate (CR + PR + SD) of 93.75% [Table 2]. The 2-, 4- and 6-month overall response rate (CR + PR) was 78%, 83% and 81%, respectively.
|Figure 2: The same patient of Figure 1 (a) computed tomography (CT) scan 2-month after seed implantation showed marked shrinkage in tumor size and brachytherapy seeds were in place. (b) CT scan showed metastases in lymph nodes in the mediastinum (arrow). (c) CT scan at 4-month follow-up showed that the tumor size decreased significantly and 125I seeds gathered together. (d) CT scan at 6-month follow-up showed no obvious change in tumor size as compared with that before|
Click here to view
|Table 2: Evaluation of the therapeutic effect after implantation of 125I seeds|
Click here to view
| » Discussion|| |
Despite rapid progress in treatment modalities for primary lung cancer including surgery, radiotheraphy, chemotherapy and biotherapy, the prognosis of lung cancer remains generally poor. Surgical resection remains the major approach for lung cancer at present. Unfortunately, many malignant tumors are unresectable at the time of diagnosis due to advanced stages or poor cardiopulmonary reserve. Chemotherapy is also a major palliative treatment for primary and metastatic lung tumors. Regrettably, drug resistance is the main hurdle to be addressed for its practical applications.  Recently, despite efforts to overcome the resistance to drugs and improve the chemosensitivity, the 5-year overall survival rate of patients diagnosed with lung cancer is lower than 15%. Therefore, seeking other more effective therapeutic approaches appears particularly important.
External beam radiation therapy (EBRT) is a common treatment for inoperable patients. However, high efficacy of EBRT is apparently limited to a very selected population of patients.  Stereotactic body radiation therapy (SBRT) involving extreme hypofractionation is considered superior to EBRT.  Although higher doses are shown to offer better response and better local control leading to a better survival, they are not applied to tumors involving the major vessels, main bronchi and heart due to their low tolerance to radiation.  In addition, only small lesions (typically <5 cm) can be treated, and the accuracy and reproducibility of treatment are essential. An appreciable prevalence of complications such as pulmonary toxicity and rib toxicity has been reported for SBRT.  In the present study, 11 patients had been treated previously with radiotherapy, 6 patients had severe bone-marrow depression and 4 patients experienced tumor recurrences. No bone-marrow depression, pulmonary toxicity, rib fracture, radiation pneumonitis or hemoptysis occurred in our patients who received the CT-guided brachytherapy.
Brachytherapy has been used to improve local control either alone or in combination with other treatments. High-dose irradiation is given when radioactive seeds are implanted into tumors. Characterized by attenuation over a short distance, radiation from radioactive seeds enables to deliver the maximal radiation dose to the tumor with the minimal radiation dose to the surrounding normal tissue.
About 70 years ago, the interstitial seed implantation technique using radon seeds and radium needle implants were used for the treatment of recurrent pelvic cancers. However, this method has been abandoned due to the hazards of radiation exposure from high-intensity radioisotopes and poor dose distribution in the target. Gamma rays given by low-energy 125 I seeds are concentrated in the target area with a very sharp fall-off outside the implanted volume, thus protecting the adjacent normal tissues. Additionally, with a half-life of 59.6 days, 125 I can prolong exposure of the tumor target to radiation. , Moreover, radiation-induced tumor shrinkage makes the radioactive seeds closer together, which may theoretically enhance the therapeutic benefit by natural increases in local doses. Finally, continuous low-dose radiation provided by 125 I seeds may decrease the oxygen enhancement ratio, leading to improved efficacy in hypoxic regions of the tumor.
Ricke et al.  reported that the local tumor control rate was 97% when they employed interstitial brachytherapy in 15 lung cancer patients with a median follow-up period of 5 + months. Zhang et al.  reported that the outcome of interstitial brachytherapy was even better in advanced NSCLC patients when it was used in combination with CT-guided percutaneous implantation of 125 I seeds and chemotherapy as compared with chemotherapy alone. In our study, the local control rate was only 90.5%, which is lower than that reported by previous studies. The reason may be that patients enrolled in our study are different from those in the previous studies. The lack of investigated patients may also contribute to the difference.
| » Conclusion|| |
Computed tomography-guided implantation of 125 I seeds is feasible and effective for the treatment of lung cancer patients who have received multiple other treatment modalities. The high local control rate (90.5%) is encouraging. However, there are some limitations in our study, such as the short follow-up period and the limited number of investigated patients. Therefore, large-scale studies with long-term follow-up periods are needed to confirm the effectiveness of this method.
| » Acknowledgments|| |
This study is supported by Shandong Tackle Key Problems in Science and Technology (2010GSF10245).
| » References|| |
Zahir ST, Mirtalebi M. Survival of patients with lung cancer, Yazd, Iran. Asian Pac J Cancer Prev 2012;13:4387-91.
Pan TW, Wu B, Xu ZF, Zhao XW, Zhong L. Video-assisted thoracic surgery versus thoracotomy for non-small-cell lung cancer. Asian Pac J Cancer Prev 2012;13:447-50.
Kim J, Lee SM, Yim JJ, Yoo CG, Kim YW, Han SK, et al
. Prognosis for non-small cell lung cancer patients with brain metastases. Thorac Cancer 2013;4:167-73.
Yeo UJ, Taylor ML, Dunn L, Kron T, Smith RL, Franich RD. A novel methodology for 3D deformable dosimetry. Med Phys 2012;39:2203-13.
Mirsadraee S, Oswal D, Alizadeh Y, Caulo A, van Beek E Jr. The 7 th
lung cancer TNM classification and staging system: Review of the changes and implications. World J Radiol 2012;4:128-34.
Chen YT, Feng B, Chen LB. Update of research on drug resistance in small cell lung cancer chemotherapy. Asian Pac J Cancer Prev 2012;13:3577-81.
Sharma DN, Rath GK, Kumar S, Bhatla N, Gandhi AK, Sharma P, et al.
Postoperative radiotherapy following inadvertent simple hysterectomy versus radical hysterectomy for cervical carcinoma. Asian Pac J Cancer Prev 2011;12:1537-41.
Katz AJ, Santoro M, Ashley R, Diblasio F, Witten M. Stereotactic body radiotherapy as boost for organ-confined prostate cancer. Technol Cancer Res Treat 2010;9:575-82.
Dawood O, Mahadevan A, Goodman KA. Stereotactic body radiation therapy for liver metastases. Eur J Cancer 2009;45:2947-59.
Linda A, Trovo M, Bradley JD. Radiation injury of the lung after stereotactic body radiation therapy (SBRT) for lung cancer: A timeline and pattern of CT changes. Eur J Radiol 2011;79:147-54.
Ricke J, Bretschneider T, Peters N, Hass P,. Update on interstitial brachytherapy. Der Radiologe 2012; 52: 70-73.
Zhang S, Zheng Y, Yu P, Yu F, Zhang Q, Lv Y et al. The combined treatment of CT-guided percutaneous 125I seed implantation and chemotherapy for non-small-cell lung cancer. Journal of cancer research and clinical oncology 2011; 137: 1813-1822.
[Figure 1], [Figure 2]
[Table 1], [Table 2]
|This article has been cited by|
||Stereotactic Ablative Brachytherapy: Recent Advances in Optimization of Radiobiological Cancer Therapy
| ||Hui Xue, Bin Qiu, Hao Wang, Ping Jiang, Olga Sukocheva, Ruitai Fan, Lixiang Xue, Junjie Wang |
| ||Cancers. 2021; 13(14): 3493 |
|[Pubmed] | [DOI]|
||Comparison of Image-Guided Iodine-125 Seed Interstitial Brachytherapy and Local Chemotherapy Perfusion in Treatment of Advanced Pancreatic Cancer
| ||Li Zhou, Hui Yang, Linjun Xie, Jiantong Sun, Jun Qian, Lifei Zhu |
| ||Journal of Investigative Surgery. 2020; : 1 |
|[Pubmed] | [DOI]|
||Radiation-related Adverse Effects of CT-guided Implantation of 125I Seeds for Thoracic Recurrent and/or Metastatic Malignancy
| ||Zhe Ji,Yuliang Jiang,Fuxin Guo,Ran Peng,Haitao Sun,Panfeng Wang,Jinghong Fan,Junjie Wang |
| ||Scientific Reports. 2019; 9(1) |
|[Pubmed] | [DOI]|