Study design and patients
This was a retrospective study of patients with small metastatic tumors in the lung treated with CT-ISI between December 2013 and March 2018 at the Department of Interventional Radiology of the Affiliated Hospital of the University. This retrospective study was approved by the ethics committee of the Affiliated Hospital of the University. The use of patient information was approved by our institutional review board, which waived a requirement for patient informed consent.
The inclusion criteria were: 1) highly suspected diagnosis of metastatic tumors in the lung based on patients' history of cancer and on clinical, imaging, and/or pathological characteristics of the lesions; 2) underwent CT-ISI; 3) the largest diameter of the lesions was <2.5 cm; and 4) complete clinical data.
The exclusion criteria were: 1) emphysema or a large lung bubble near the metastasis; 2) unstable cardiorespiratory function, blood coagulation disorder, or active infection; or 3) Eastern Cooperative Oncology Group performance status (ECOG PS) ≥3.
Grouping
The patients were divided into two groups according to whether a 5-ml syringe was used as a guide during CT-ISI or not.
CT-ISI
The radioactivity of the iodine-125 seeds (CIAE-6711; Chinese Atomic Science Institution, Beijing, China) used in this study was 2.59×107 Bq. The ISI treatment plan system (TPS; KL-SIRPS-3D) and gun-type implantation device were from the Institute of Medical Science and Technology (Beijing, China). Disposable 5-ml syringes and 18 G puncture needles (Cook Medical, Bloomington, IN, USA) were used for local infiltration anesthesia and puncture. The lung lesions were scanned by CT at 3-mm intervals using a 64-slice CT scanner (Siemens, Germany) for intraoperative and postoperative follow-up.
One radiation physicist and two interventional radiologists generated the treatment plan (TP) for each pulmonary metastasis using the TPS in order to determine the number of seeds to be implanted and the ideal implantation location. The planning target volume was defined as 0.5 cm of expansion external to the gross tumor volume. The prescribed dose was 135 Gy, which was chosen based on our previous studies.[12, 13] Local anesthesia was administered with a 5-ml syringe (2% lidocaine; Yimin, Yichang, China) at the body surface location marker (Figure 1 A,B, Figure 2 A and Figure 3 A). An 18 G needle was then punctured into the pulmonary metastasis with or without the 5-ml syringe as a guide (Figure 1 C,D,E,F, Figure 2 B,C and Figure 3 B,C,D) and Iodine-125 seeds were implanted (Figure 2 D and Figure 3E). As in our previous study, the seeds were placed 0.5-0.8 cm apart in line with the TPS to the best extent possible. The seed radiotherapy treatment radius of iodine-125 is about 1 cm, according to the manufacturer's instructions. Thus, for lesions ≤1 cm, the entire lesion can be fully included in the treatment range even if the lesion is only punctured at the edge. For larger lesions, if the puncture location could not fully cover the lesion, the puncture was considered failure and had to be performed again after adjusting the position or path of the puncture needle. Post-implantation dose verification was performed to verify the therapeutic dose according to the TPS and assessment of peripheral tissue (bronchial and vascular) damage. A D90 (dose contains 90% of the target volume) value of >135 Gy at the last implantation was regarded as successful.
Follow-up and evaluation of clinical effectiveness
Patients were monitored using continuous electrocardiogram for 6 h after seed implantation, with appropriate symptomatic treatment for chest tightness, chest pain, blood in sputum, vomiting, fever, etc. Generally, the patients were discharged within 2 days after implantation. The final follow-up was on March 31st, 2018. The follow-up time was calculated from the first-ever treatment of pulmonary metastases with CT-ISI to the last follow-up or death. Chest CT enhancement examinations were used to evaluate the maximum diameter of the metastatic pulmonary lesions (Figure 3F), to screen for new lesions, and to assess radiation-induced lung injury at 1, 3, 6, and 12 months after CT-ISI. Radiation lung injury was evaluated according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events, version 4.0 (CTCAE 4.0). [19]
Statistical analysis
Continuous variables were expressed asmeans ± standard deviations (SD) and were analyzed using the Student t-test. Categorical variables were presented as frequencies and percentages and were analyzed using the chi-square test or Fisher's exact test, as appropriate. Two-sided P-values <0.05 were considered statistically significant. GraphPad Prism, version 5 (GraphPad Software Inc., San Diego, CA, USA) was used for statistical analysis.