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Year : 2020  |  Volume : 16  |  Issue : 7  |  Page : 1549-1554

Chinese expert consensus workshop report: Guideline for permanent iodine-125 seeds implantation of primary and metastatic lung tumors (2020 edition)

1 Imaging and Interventional Center, Sun Yat-sen University Cancer Center, Guangzhou, China
2 Department of Radiation Oncology, Cancer Centre, Peking University Third Hospital, Beijing, China
3 Department of Radiology, Southeast University, Zhongda Hospital, Nanjing, China
4 Department of Interventional Medicine, The First Hospital Affiliated to AMU (Southeast Hospital), Tianjin, China
5 Department of Thoracic Surgery, The Second Hospital of Tianjin Medical University, Tianjin, China
6 Department of Thoracic Surgery, Shaanxi Provincial Cancer Hospital, Xi'an, China
7 Department of Oncology, Hebei General Hospital, Shijiazhuang, China
8 Department of Oncology, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
9 Department of Thoracic Surgery, The Second Hospital of Shandong University, Jinan, China
10 Department of Respiration, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, China
11 Department of Oncology, The Affiliated Zhongshan Hospital of Dalian University, Dalian, China
12 Department of Interventional Medicine, The Second Hospital of Shandong University; Interventional Oncology Institute of Shandong University, Jinan, China
13 Department of Oncology, Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
14 Department of Medical Oncology, The First Hospital of China Medical University, Shenyang, China
15 Laboratory Medicine Center, The Second Hospital of Shandong University, Jinan, China

Date of Submission03-Aug-2020
Date of Decision25-Aug-2020
Date of Acceptance01-Oct-2020
Date of Web Publication9-Feb-2021

Correspondence Address:
Chuanxin Wang
Laboratory Medicine Center, The Second Hospital of Shandong University, Jinan, CN-250033
Yuliang Li
Department of Interventional Medicine, The Second Hospital of Shandong University; Interventional Oncology Institute of Shandong University, Jinan, CN-250033
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_1096_20

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 > Abstract 

Surgery remains the first option for curing early stage lung cancer. However, many patients are diagnosed at an advanced stage, and thus miss the chance to undergo surgery. As such patients derive limited benefits from chemotherapy or radiotherapy, alternatives based on local control have emerged, including iodine-125 seed implantation. The Interstitial Brachytherapy Society, Committee of Minimally Invasive Therapy in Oncology, the Chinese Anti-Cancer Association organized a group of multidisciplinary experts to revise the guidelines for this treatment modality. It aims to standardize iodine-125 seed implantation procedures, inclusion criteria, and outcome assessment to prevent and manage procedure-related complications.

Keywords: Guidelines, implantation, iodine-125, lung malignancy

How to cite this article:
Zhang F, Wang J, Guo J, Huang X, Guan Z, Lei G, Wang J, Ye X, Zhao X, Wang J, Wang R, Liu B, Zhou Q, Zhao M, Wang C, Li Y. Chinese expert consensus workshop report: Guideline for permanent iodine-125 seeds implantation of primary and metastatic lung tumors (2020 edition). J Can Res Ther 2020;16:1549-54

How to cite this URL:
Zhang F, Wang J, Guo J, Huang X, Guan Z, Lei G, Wang J, Ye X, Zhao X, Wang J, Wang R, Liu B, Zhou Q, Zhao M, Wang C, Li Y. Chinese expert consensus workshop report: Guideline for permanent iodine-125 seeds implantation of primary and metastatic lung tumors (2020 edition). J Can Res Ther [serial online] 2020 [cited 2021 May 16];16:1549-54. Available from: https://www.cancerjournal.net/text.asp?2020/16/7/1549/308755

 > Introduction Top

Globally, lung cancer is the top malignant tumor[1] with approximately 1,855,900 new cases and 1,589,900 deaths in 2012. China's situation is severe. According to the reported estimates in 2015,[2] the annual incidence of lung cancer was 57.26/100,000, and the annual mortality was 45.87/100,000 with the largest absolute number globally. Its pathogenic factors include smoking, air contamination, and heredity.[3] For its early stage, including small cell lung cancer (SCLC) or non-SCLC (NSCLC), surgery is the first option for cure.[4] However, many patients are diagnosed at an advanced stage and have no chance of surgery. These patients will receive limited benefits from chemotherapy or radiotherapy, and many alternatives based on local control have emerged, including permanent iodine-125 seed implantation, thermal ablation, and photodynamics therapy. Studies on iodine-125 seed implantation have been reported treating lung cancer, and many patients benefit from this alternative technique.[5],[6],[7],[8],[9] Furthermore, iodine-125 seed implantation has also been shown to be effective on metastatic lung cancer.[10],[11],[12],[13],[14]

In 2014, Comprehensive Interventional Physicians Society of the Shandong Medical Association and Interventional Oncology Society of the Shandong Anti-Cancer Association organized experts on minimally invasive treatment of tumors to discuss standardized processes for CT-guided iodine-125 seed implantation. Therefore, “Shandong Expert Consensus for Permanent Iodine-125 Seeds Implantation of Primary and Metastatic Lung Tumors” was summarized and published in “Shandong Medical Journal” in 2015.[15] In 2018, the Interstitial Brachytherapy Society, Professional Committee of Minimally Invasive Treatment of Cancer of the Chinese Anti-Cancer Association organized multidisciplinary experts to revise the guidelines, and summarized the “Chinese Expert Consensus Workshop Report: Guidelines for permanent iodine-125 seed implantation of primary and metastatic lung tumors,” which was published in “Thoracic Cancer” in 2019.[16]

Both guidelines greatly contributed to developing and standardizing iodine-125 seed implantation of lung tumors. However, many shortcomings have been found in these guidelines and further improvements are needed. Therefore, the Interstitial Brachytherapy Society, Professional Committee of Minimally Invasive Treatment of Cancer of the Chinese Anti-Cancer Association organized a group of multidisciplinary experts to revise these guidelines for permanent iodine-125 seed implantation of primary and metastatic lung tumors.

 > Concept and Principle of Iodine-125 Brachytherapy Top

As a brachytherapy, radioactive seeds are implanted directly into the lesion, and kill tumor cells by consistently releasing rays. Iodine-125 is the most common permanent implanted seeds with a size of 4.5 mm × 0.8 mm and an envelope of nickel titanium alloy. γ-rays with energy lower than 0.0355 MeV could inhibit cell proliferation and angiogenesis, induce apoptosis, and kill tumor cells.[17],[18],[19]

 > Implanting Modalities Top


Percutaneous iodine-125 seed implantation was usually performed under computed tomography (CT) or ultrasound guidance. For lung tumors, CT is a more preferred technique.[20] Ultrasound could be used for some lesions near or adhere to chest wall.[21] Magnetic resonance imaging (MRI) has shown considerable value in percutaneous biopsy[22] and target localization,[23] and may be one alternative guiding modality of iodine-125 seed implantation for lung tumors.

Image and three dimensional printing non-coplanar template guided

Recently, three dimensional (3D) printing non-coplanar template (PNCT) technology has been widely used in the field of iodine-125 seed implantation for treating malignant tumor,[24] including head and neck tumors, pancreatic cancer, recurrent rectal cancer, spinal tumors, recurrent soft tissue tumor, and lung tumors.[25] However, 3D PNCT guided iodine-125 seed implantation should overcome the influence of rib obstruction and respiratory mobility. There was no solution for promotion.

Electronic fibrobronchoscope: Mainly used for

(1) Early stage of central lung cancer;[26] (2) localized intratracheal tumor, which cannot be treated with surgery or other radical therapy.[27],[28]

During surgery

(1) Lung tumor which is adjacent to hilum, large vessels, or heart, and could not be treated with radical resection[29] and (2) unresectable lung tumor.[30]

Endobronchial ultrasound guided

The ultrasonic probe in the front of the lens could clearly show the relationship between blood vessels, lymph nodes, and tumors outside the airway. Under the real-time monitoring of ultrasound images, iodine-125 seed implantation can avoid damage to the surrounding large blood vessels and improve the safety and accuracy of seed implantation.[31]

Other modalities

Such as iodine-125 seed implantation during robot-assisted surgery.[32],[33]

 > Principles of Iodine-125 Seed Implantation Top

Multi-disciplinary team and individualized treatment

An effective and reasonable treatment plan should be made after consulting physicians in the Department of Thoracic Surgery, Respiratory, Oncology, Radiation Oncology, and Interventional Medicine.

Treatment plan

Delineate target area according to lung window,[34] as well as organs at risk (OARS). Select appropriate prescription dose (PD) and activity of seeds, and make treatment plan with the treatment planning system (TPS).

Implant seed into the tumor under CT guidance, and perform intraoperative dose optimization if necessary.

Bilateral lesions should be treated separately each time.

Evaluate dose of target tumor with dose–volume histogram (DVH) and isodose profile after the procedure.

Observe complications including hemorrhage, radiation pneumonitis during follow-up after the procedure.[35]

 > Indications and Contraindications Top


  1. Primary lung cancer: (1) not candidates for surgery due to low cardiopulmonary reserve or old age;[20],[36] (2) refused to accept surgery; (3) recurrent and unresectable tumor;[8],[34] (4)residual or progressed tumor after surgery, radiotherapy, or chemotherapy;[37] (5) to get tumor-free boundary with thermal ablation[38] or surgery;[39] (6) Karnofsky performance status (KPS) >60, and predicted life span >6 months;[17](7) the diameter of the largest tumor <7 cm[17]
  2. Metastatic lung cancer: (1) unilateral lesions with the number ≤3 and the diameter ≤5 cm;[17] (2) Bilateral lesions should be treated separately with the number ≤3 and the diameter ≤5 cm.[17]


(1) cachexia with multi-functional failure; (2) intractable infection or radiation inflammation around the lesion;(3) skin infection or ulceration around the puncture site;(4) severe coagulation disorders or anemia; (5) ipsilateral massive malignant pleural effusion; (6) KPS score <60; (7) predicted life span ≤6 months.

 > Preoperative Preparation and Examination Top

Evaluation of patients

Whether the patient is appropriate for iodine-125 seed implantation should be determined after MDT consultation by checking the history, physical, and imaging examinations [Figure 1]. Enhanced CT of chest with the slice thickness of 5 mm 1 week before the procedure is necessary to detect the size, location, and distance to other organs, vessels, and trachea of the tumor. For the cases requiring 3D PNCT, delineate anchor points on the skin. Necessary imaging examinations should be performed to detect metastasis and determine the TNM stage, including Positron Emission Tomography – Computed Tomography (PET-CT).
Figure 1: Flow Chart of Iodine-125 Seed Implantation for Lung Tumors

Click here to view


Percutaneous or fiberbronchoscopic biopsy is necessary before iodine-125 seed implantation.[40]

Treatment planning system

After importing the data of chest enhanced CT into TPS, delineate clinical target volume (CTV) according to images on the lung window (with width of 1000 HU, level of −650 HU and slice thickness of 5 mm).[34] The recommended activity of seed is 0.6–0.8 mci, and the PD is 120–160 Gy.[41] Planning target volume (PTV) should cover CTV and one more 1 cm beyond the margin. OARS around the tumor should also be delineated. Order iodine-125 seeds according to TPS plan.[42] Design 3D-PNCT if necessary. MRI[23] or PET-CT[43] is recommended to delineate target volume when atelectasis exists. Dose–volume histogram is used to evaluate plan dose plan.

Laboratory examinations

Include blood count, urine, stool, blood coagulation, liver and kidney function, blood glucose level, tumor markers, electrocardiogram (ECG), echocardiography, and lung function test.

Drugs and electrocardiogram monitoring

Anesthesia, analgesia, antitussive, hemostasis, vasodilator, and antihypertensive drugs and monitoring devices should be prepared before the procedure.

Patients preparation

Patients or their mandatary should sign informed consent, be fasted for 4 h before local anesthesia or 6 h before intravenous general anesthesia. Oral antitussive is necessary before the procedure.

 > Operation Processes Top

Body position and anesthesia

Select appropriate body position according to tumor location and performance status of the patient. Vacuum cushions were used to fix patients. Local or intravenous general anesthesia is selected according to the practice of local hospital. Disinfect the operation field with strict implementation of aseptic manual. Planar template should be fixed to the frame, while 3D PNCT should be fixed according to TPS plan and anchor points on skin.[44]

Iodine-125 seed implantation

Take CT guidance as an example. CT with a slice thickness of 0.5 cm was performed before the procedure to identify the tumor location and mark operation field. Select appropriate intercostal space as puncture plane, and determine the puncture site, angle, and depth. Auxiliary technologies, such as bone drilling[45] or artificial pneumothorax[10],[46] could be used for cases where bone acts as a barrier for puncture. Insert the puncture needles into the tumor under CT guidance, and implant iodine-125 seeds according to TPS plan. The distance among puncture needles is usually 1–1.5 cm. The puncture of needles could be accomplished at once or on fractionation procedure. After all needle tips reach the distal edge of the tumor, retrace the needle with equal distance or according to TPS plan, and implant iodine-125 seeds. CT scan was recommended to be repeated during the procedure to ensure that the seeds were implanted as the TPS plan. Revise the implantation plan if necessary. After implantation, re-scan the entire lung, and check the distribution and number of iodine-125 seeds in every plane. If there is cold area, implant some more seeds to match the dose requirement of TPS plan. Check if there are complications including pneumothorax or hemorrhage,[47] and treat it if necessary, such as percutaneous drainage. Import data of CT scan after the procedure into TPS, and verify if the dose meets the dose requirement of preoperative plan.[48]

Monitoring during the procedure

Heart rate, blood pressure, and blood oxygen saturation are carefully monitored. Consciousness, breathing, and symptoms of patients, including pain, cough, or hemoptysis are closely observed. Treat it if necessary.

Postoperative treatment

Patients should be escorted back to the ward by doctors. ECG monitoring and oxygen inhalation are necessary until the patient's condition is stable. X-ray examination or chest CT should be repeated 24 h after the procedure, checking if there is pneumothorax, hemothorax, or seed migration.[46]

 > Adverse Reactions and Complications Top

Adverse reactions and complications after seed implantation should be evaluated according to Common Terminology Criteria for Adverse Events,[49] and radioactivity response evaluation criteria Radiation Therapy Oncology Group (RTOG)/EORTC1987 from the U. S. RTOG.

  1. Pneumothorax: No medical treatment is recommended for slight pneumothorax, especially when there is no symptom. If the compression ratio of the affected lung exceeds 30% and patients suffer from suffocating or dyspnea, thoracic drainage is recommended
  2. Hemorrhage: (1) Lung hemorrhage: For patients with bloody sputum or hemoptysis, medicine (such as pituitrin, reptilase, aminomethylbenzoic acid, or ethamsylate) should be used. Bronchial artery embolization is recommended if necessary. (2) Hemothorax: The reasons include damage of intercostal artery, internal thoracic artery, or vessels inside the lung, which cause bleeding into the thoracic cavity. If the amount is more than 500 ml, blood transfusion and fluid resuscitation are recommended. Arteriography and embolization are necessary if the above treatments do not work. Surgery is recommended if necessary, especially when the blood pressure and heart rate are unstable
  3. Pleural reaction: Relatively rare. Main symptoms include nagging cough, dizzy, sweatiness, pale face, palpitation, hypotension, chest constriction, and conscious disturbance. The operation should be suspended immediately. Lay the patient on the bed, keep warm, and monitor the heart rate, blood pressure, and consciousness. After rest or psychological counseling, some patients may recover soon. For patients with hypoglycemia or unstable vital signs, oxygen inhalation and glucose administration are recommended. Adrenaline should be administered to avoid shock if necessary
  4. Infection: Relatively rare. Main symptoms include fever, leukocytosis. Antibiotics administration is recommended, and strict sterile manipulation can avoid infection
  5. Puncture tract metastasis: Relatively rare.[41] Surgery or repeated iodine-125 seed implantation may work. Chemotherapeutics (such as 5-fluorouracil or tegafur) injection through puncture needles would reduce the incidence
  6. Seed migration: Iodine-125 seeds may migrate to distal bronchia or thoracic cavity.[8] It should be carefully screened
  7. Local radiation pneumonitis and radiation pulmonary fibrosis: Rare. It may occur in patients who received repeated iodine-125 seed implantation
  8. Other rare complications: Such as pulmonary embolism, aeroembolism and nerve damage. The treatment depends.

 > Follow-up and Effect Evaluation Top


Enhanced CT of chest is recommended at 1, 3, 6, 9, 12, 18, 24, 30, 36, 42, 48, 54, and 60 months. It should be repeated once a year for 5 years. PEC-CT or MRI would be applied if necessary.

Effect evaluation of local lesion

It is according to Response Evaluation Criteria in Solid Tumor Version 1.1.[50] Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether a target or nontarget) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm.(Note: the appearance of one or more new lesions is also considered progression). Stable Disease: Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

Clinical effect evaluation

Based on the local effect evaluation, the state of survival should be recorded in 1, 2, 3, and 5 years. Meanwhile, pay attention to Karnofsky Performance Status (KPS), pain relief rate, and drug administration of the patient.

 > Iodine-125 Seed Implantation With Other Therapies Top

Many combined treatments have been used in treating lung tumors, including iodine-125 seed implantation with surgery,[29] chemotherapy,[8] bronchial artery chemoembolization,[51] radiotherapy,[52] and targeted drugs. Iodine-125 seed implantation with chemotherapy could significantly prolong the disease progression free survival (PFS) and enhance the disease control rate (DCR) with no increased side effects.[8] For patients with advanced lung cancer after first-line radiotherapy and chemotherapy, iodine-125 seed implantation with bronchial artery chemoembolization has achieved satisfactory responses, which can prolong PFS of patients.[51] Iodine-125 seed implantation with radiotherapy could also enhance PFS and DCR. Tyrosine-kinase inhibitor (TKI) is one of the main methods for treating advanced NSCLC with epidermal growth factor receptor mutations. Despite the initial response, most patients ultimately develop acquired resistance to TKIs after 1-1.5 years. Iodine-125 seed implantation with TKIs has shown efficacy for treating patients with oligoprogressive disease associated with long PFS and overall survival.

 > Radiation Protection after The Procedure Top

Radiation protection after iodine-125 seed implantation should follow the expert consensus from Chinese Anti-Cancer Association.[53] Contact within 50 cm is prohibited in at least 2 months after the procedure, and the patients should wear a lead pad for at least 4 months.[54],[55],[56]

 > Technology Access Top

Technology access should follow the management practice from the Chinese Medical Doctor Association and Chinese Anti-Cancer Association.[57]

Financial support and sponsorship

National Natural Science Foundation of China (11971269), Key Research & Development Plan of Shandong Province (2019GSF108105), National Science Fund for Distinguished Young Scholars of China (61625102), National Key R&D Program of China (2016YFC1303800), Science and Technology Project of Jinan Health Committee (2020-3-65).

Conflicts of interest

There are no conflicts of interest.

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