|Year : 2019 | Volume
| Issue : 4 | Page : 793-800
Feasibility of three-dimensional-printed template-guided 125I seed brachytherapy and dosimetric evaluation in patients with malignant tumor
Hongtao Zhang1, Devjoy Dev2, Huimin Yu1, Xuemin Di1, Yansong Liang1, Lijuan Zhang1, Xiaoli Liu1, Jinxin Zhao1, Zezhou Liu1, Aixia Sui1, Juan Wang1, Man Hu3
1 Department of Oncology, The Hebei General Hospital, Shijiazhuang, China
2 Department of Bioengineering, Imperial College London, South Kensington, London, United Kingdom
3 Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Jinan; Department of Radiation Oncology, Shandong Province Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong Academy of Medical Sciences, Shandong, China
|Date of Web Publication||14-Aug-2019|
Department of Oncology, The Hebei General Hospital, Shijiazhuang
Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Jinan
Source of Support: None, Conflict of Interest: None
Objective: The objective of the study is to test whether three-dimensional (3D)-printed template can be used reproducibly for guiding malignant tumors brachytherapy and study the dosimetric consistency and adequacy between pre- and post-plan.
Materials and Methods: Between January and December 2016 in our hospital, a total of 14 patients underwent 3D-printed template-guided brachytherapy. All the patients were fixed into position using a vacuum cushion before undertaking a computed tomography (CT) scan. After the preplan was designed, the templates were printed. The tumors were punctured through predesigned needle holes. Following this, another CT scan was used to confirm the locations of needles, and then the 125 I radioactive seeds were implanted into the tumor according to the preplan. Postplan was performed after the operation. Data of the D90 (minimum absorbed dose of 90% target volume), V90 (90% prescription dose coverage volume percentage of target volume), V100, V150, and seed number pre- and post-operation were collected and compared.
Results: The mean D90, V90, V100, V150, and seed number preoperation were 94.96 ± 16.43 Gy, 94.64% ± 1.43%, 91.21% ± 1.59%, 65.01% ± 5.78%, and 46.67 ± 21.87, respectively. The mean D90, V90, V100, V150, and seed number postoperation were 91.97 ± 17.54 Gy, 93.35% ± 2.45%, 89.35% ± 3.21%, 63.40% ± 6.36%, and 46.60 ± 22.85, respectively. No significant difference between pre- and post-operation was observed across the data (P >0.05).
Conclusion: For immobilized malignant tumors, 3D-printed template can be used reproducibly. The dose parameters in preplan can be achieved easily and satisfactorily by 3D-printed template guided brachytherapy, and it may become an easily reproducible standardized procedure in the future.
Keywords: 125I isotopes, brachytherapy, radiation dosage, template, three-dimensional-printed
|How to cite this article:|
Zhang H, Dev D, Yu H, Di X, Liang Y, Zhang L, Liu X, Zhao J, Liu Z, Sui A, Wang J, Hu M. Feasibility of three-dimensional-printed template-guided 125I seed brachytherapy and dosimetric evaluation in patients with malignant tumor. J Can Res Ther 2019;15:793-800
|How to cite this URL:|
Zhang H, Dev D, Yu H, Di X, Liang Y, Zhang L, Liu X, Zhao J, Liu Z, Sui A, Wang J, Hu M. Feasibility of three-dimensional-printed template-guided 125I seed brachytherapy and dosimetric evaluation in patients with malignant tumor. J Can Res Ther [serial online] 2019 [cited 2019 Nov 20];15:793-800. Available from: http://www.cancerjournal.net/text.asp?2019/15/4/793/264285
| > Introduction|| |
The implantation of 125 I radioactive seeds is widely known as a permanent brachytherapy method for cancers of various histological types, such as glioma, head and neck tumor, sarcoma, lung cancer, lymphatic metastasis, digestive system neoplasm, gynecological cancer, and prostate cancer.,,,,,,, Among the various types of tumors,125 I seed brachytherapy is a standard and first-line therapy for prostate cancer in the United States. As a permanent implant technique, the radioactive seeds are directed into the tumor volume through the needles which are punctured into the target tissue area, and the radioactive sources are retained inside the patient's body for the total decay lifetime of the radioactive material. The main advantage for this form of brachytherapy is that the entire procedure can be completed in one continuous stretch, for example, one overnight stay at the hospital. However, the primary drawback is that the seeds are difficult to accurately implant into the target according to the preplan. Therefore, it has become increasingly important to introduce radioactive materials accurately into the targeted region for the effectiveness of the treatment.
Image guidance is the most reliable method to guarantee the implantation of the seeds into the target. However, under image guidance, it is difficult for doctors to insert the needles into the correct location of the tumor according to preplan. Dr. Holm was the first to combine transrectal ultrasound and a template to guide seed implantation in the prostrate 35 years ago. Using ultrasound and template preoperative planning, the application can ensure that the prostate reaches the expected standard, showcasing that the post- and pre-operative planned dose has very good consistency in patients at early stages of prostate cancer. Although this is a reliable approach for implanting seeds into the prostate, because of the limitation of ultrasound and the unique anatomical structure of the pelvis, it is difficult to use the method in other parts of the body. For seed implantation in cases of lung cancer, ultrasound is unsuitable because of ribs in the thoracic wall and air in the lung. Therefore, computed tomography (CT) was introduced for guidance in cases of lung cancer because of its high resolution of bone, air, and soft tissue. However, with CT guidance and free-hand needle insertion, doctors cannot insert many needles at 1 time into the tumor according to the preplan, which leads to a large deviation in dose between pre- and post-plan. Huo et al. have created a plane template for seed implantation in lung cancer guided by CT scan according to the method of prostate brachytherapy using template. The clinical results were better than that of free-hand implantation under CT guidance. However, all the needles have to be placed in parallel with the plane template, and therefore, this method is not fit for the tumors in complicated anatomic sites with a large number of blood vessels; intestines; bones; and organs at risks (OARs), such as the head and neck, abdomen, and pelvic region, at risk. Therefore, recent studies have highlighted the need for needles to be inserted into the tumor at any angle necessary to avoid the OARs.
Huang et al. used a type of treatment planning system (TPS) to design an individual template which included several parts with different directions. The rapid forming machine was used to make the template. The tumors in the head and neck could then be punctured in different directions under the guidance of the template. However, this approach merely organized several plane templates together, and the needles still remained parallel in every part of the individual templates. Furthermore, because of the limitation of the TPS and template-making technique, it is complicated and time-consuming to make a template. With the development of clinical imaging, computer, and three-dimensional (3D) printing technology, our previous study has shown that using 3D printing technique to make the template for tumors not only in the head and neck but also for thoracic and abdominal cancer. This approach is much faster and was performed using the Prowess TPS combined with a 3D printer. Under the guidance of a 3D-printed template, needles can be efficiently inserted at any arbitrary angle into the target, avoiding blood vessels and bones, and at the same time accurately reproducing the needle positions according to the preoperative plan. One of the outcomes of this method is a reduction in error in the needle punctures. The distribution of the radioactive seeds was more confined to the tumor, and therefore, there is a strong possibility of this method being compatible with the dosimetric requirements. However, whether it can be used reproducibly is unknown. To the best of our knowledge, there have been only a few studies on the use of 3D-printed template-guided 125 I seed brachytherapy in parts of the body other than the prostrate.
In the present study, Prowess TPS and 3D printer were used to make a template to guide seed implantation in cases of head and neck primary tumor and lymphatic metastasis, thoracic neoplasm, digestive system neoplasm, and gynecological cancer. The purpose was to test whether 3D-printed template can be used reproducibly in these tumors above and to study the dose consistency between pre-plan and post-plan.
| > Materials and Methods|| |
Fourteen patients with malignant tumor, validated by pathological evidence, were enrolled from January to December 2016 in our hospital. Before any therapy was performed, all patients received standard pretreatment evaluations, including conventional physical examination, laboratory tests, contrast-enhanced CT. When necessary, magnetic resonance imaging, single-photon emission CT, and additional fluorodeoxyglucose positron imaging tomography/CT scans were performed. The inclusion criteria included age from 18 to 80 years; the World Health Organization performance status 0–1; no abnormalities on blood, biochemical, and coagulation examination. The exclusion criteria were major organ dysfunction, acute or chronic infections, severe organ and coagulation dysfunction, mental disorder or a history of mental illness, other distant metastases, and pregnancy. All the 14 patients were treated by 3D-printed template-guided brachytherapy. Patients and tumors characteristics have been summarized in [Table 1].
|Table 1: The information of 14 patients and treatment before brachytherapy|
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Patients' written informed consent was obtained after the Research Ethics Committee of our hospital approved this study.
Preoperative planning and printing three-dimensional template
One week before the operation, patients were immobilized with the vacuum cushion to what was referred to as the patient operative position. A position line was drawn using the CT laser on the surface of the patient's skin around the tumor location, and two marks were made 3–4 cm away on this line. An enhanced CT scan was performed to obtain image series with a slice thickness of 5 mm. Then the image series was transferred to Prowess TPS (Panther Brachy version 5.0 TPS, Prowess Inc., Concord, CA, USA) to create Brachy Stereo-Seed preplan. In TPS, the target volume and OARs were delineated carefully according to the CT findings, and seed activity was selected. Following this, the needles were designed, and seeds were loaded [Figure 1]a. The Stereo-Seed plan was committed when the target and OAR dose reached the prescription dose, and D90, V90, V100, V150, seed number, and dose-volume histogram (DVH) was generated. The CT image series and space coordinates of all the needle locations were then exported. The patient's area of skin, the template to be printed, and needle coordinates were reconstructed in Prowess TPS [Figure 1]b. According to the clinical requirement, the size of needle puncture holes was defined, and the 3D printing output file was generated. The 3D printer (Unicorn 3DSL450M, Beijing Unicorn Science and Technology Ltd., Bei Jing, China) was used to print the 3D template [Figure 2]. 1 day before operation, the 3D-printed template was disinfected and sterilized.
|Figure 1: (a) Preplan made by treatment planning system to determine the number, location of the radioactive seeds implanted and the needles direction and depth, (b) three-dimensional reconstructed the template, skin surface, needles, tumor, and organ at risk|
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Seed activity measurement
A radioactivity meter (RM-905a well-type ionization chamber, National Institute of Metrology, Bei Jing, China) was used to measure the activity of radioactive 125 I seeds (model, 6711-99; activity, 0.3–0.7 mCi; length, 4.5 mm; diameter, 0.8 mm; average energy, 27–35 keV; Beijing Zhibo Pharmaceutical Company, Bei Jing, China) before the operation. If activity error was <5%, all seeds would be blocked in the shell of brachytherapy applicator for disinfection.
During the operation, the vacuum cushion was used to fix the patient into position, ensuring the position was the same as that during the preoperative planning (by referring to the photograph of patient immobilization acquired previously). The correct CT laser position was ensured such that the laser line aligns with the line drawn on patient's skin surface preoperatively. The 3D-printed template was disinfected with formaldehyde through a fumigation process and then was secured on the patient's body surface based on the markers attached. A CT scan was performed to confirm that the template location was correct, and then the needles were fed into the tumor target based on the position of the template holes [Figure 3]. After inserting all the needles, a CT scan was performed again to confirm the needle positions [Figure 4]. Finally, the radioactive seeds were implanted according to the preoperative plan.
|Figure 3: Photograph of the template in position on the patient and with the seed-loaded needles inserted to the planned depth|
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|Figure 4: Computed tomography scan during the operation to confirm the needle positions|
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Postoperative verification plan
After finishing the seed implantation process, another CT scan was performed immediately, with a slice thickness of 5 mm. The images were then transferred into the Prowess TPS to verify the plan. The software was used to contour the target volume of the OARs, as well as identify the implanted seeds. Subsequently, the curve of dose distribution [Figure 5] and D90, V90, V100, V150, seed number, and DVH [Figure 6] were determined.
|Figure 5: Postplan made by treatment planning system and the isodose line distribution|
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|Figure 6: Dose-volume histogram calculated by treatment planning system in pre- plan and post-plan|
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For dosimetric evaluation of the quality of implants, the following two criteria were used.
- The Prostate Brachytherapy Program at the British Columbia Cancer Agency in Canada defined an implantation as:
- Good implant if V100>85%
- Suboptimal if V100 of 75–85%
- Poor implant if V100<75%
The Prostate Brachytherapy Community regards implants with a D90 >90% and a V100 >80% as adequate. An adequate V150 was defined as <60% for 125 I seeds.
According to these two criteria, the dose parameters were analyzed to determine whether 3D-printed template guided 125 I seed brachytherapy satisfies the criteria.
The SPSS version 13.0 statistical software (IBM, Armonk, NY USA) was used for data analysis. Paired t-test was used to analyze the statistical difference in the D90, V90, V100, V150, and seed numbers between the preoperative and postoperative conditions; P < 0.05 was defined as statistically significant.
| > Results|| |
The mean preoperative D90, V90, V100, V150, and seed numbers were 94.96 ± 16.43 Gy, 94.64% ± 1.43%, 91.21% ± 1.59%, 65.01% ± 5.78%, and 46.67 ± 21.87, respectively. The mean postoperative D90, V90, V100, V150, and seed numbers were 91.97 ± 17.54 Gy, 93.35% ± 2.45%, 89.35% ± 3.21%, 63.40% ± 6.36%, and 46.60 ± 22.85, respectively. No significant difference was observed between pre- and post-operative data (P > 0.05).
All the patients were successfully operated without complications such as severe hemorrhage, pneumothorax, and fistula of intestine.
The D90 ranged from 60.91 Gy to 121.06 Gy (94.96 ± 16.43 Gy) in preplan, and from 63.06 Gy to 124.20 Gy (91.97 ± 17.54 Gy) in postplan. The D90 in preplan was slightly higher than that in postplan; however, the difference was not statistically significant (t = 2.021, P = 0.063). The V90 was 92.6%–97.4% (94.64% ± 1.43%) in preplan, and 89.5%–96.4% (93.35% ± 2.45%) in postplan. There was no difference between pre- and post-plan (t = 1.824, P = 0.090). The V100 was 89%–94.7% (91.21% ± 1.59%) in preplan, and from 83.3%–93.4% (89.35% ± 3.21%) in postplan. There was no difference between pre- and post-plan (t = 2.045, P = 0.060). The V150 was 58.6%–77.9% (65.01% ± 5.78%) in preplan, and 48.8%–76.8% (63.40% ± 6.36%) in postplan. There was no difference between pre- and post-plan (t = 2.045, P = 0.060). The dose and volume histograms for one patient are shown in [Figure 6]. Solid and dotted lines represent the doses in pre-plan and post-plan, respectively. The seed numbers were 18–90 (46.67 ± 21.87) in preplan, and 18–90 (46.60 ± 22.85) in postplan. There was no difference between pre- and post-plan (t = 0.113, P = 0.912). Comparative results of the patients' dose index are shown in [Table 2].
|Table 2: The D90, V90, V100, V150 and seeds number of pre- and post-operation|
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Based on criterion 1, 12 (85.7%) out of 14 implants were deemed of good quality, 3 (21.4%) out of 14 implants were considered suboptimal in quality, none of the implants were considered poor in quality.
Based on criterion 2, 14 (100%) out of 14 implanted doses were adequate.
| > Discussion|| |
This study demonstrates that 3D-printed template can be used reproducibly for evaluation of immobilized malignant tumors. The dose parameters in pre- and post-plan have good consistency. Although 3D-printed template is difficult to prepare and requires more work before the operation, there is a learning curve, and preparation and operation times decrease with the physician's and team's experience. In addition, many needles can be inserted into the tumor accurately without repeated CT scans and in a shorter time. The proper placement of needles may increase radiation dose coverage of the tumor and decrease operation injury and dose in OARs.
The use of a template is partly why brachytherapy can be included into the National Comprehensive Cancer Network guidelines as a standard treatment for prostate cancer.,,, If brachytherapy is to be used as a standard treatment for other tumors, there must be a reliable and repeatable procedure. Although seed brachytherapy is widely used for various body parts in China,,,,, most of related studies involve freehand-based techniques. Freehand-based brachytherapy has a high failure rate because of the poor dose consistency between pre- and post-plan. To solve this problem, physicians attempt to create and use a template in tumors located in other parts of the body. Huo et al. applied a template to guide the brachytherapy operation for lung cancer in a clinical study. Although good results were achieved, there were still some issues, for example, all the needles had to be parallel to each other, which restricted the use of the template. Huang et al. used the rapid forming machine to make the individual template necessary for head and neck tumor brachytherapy. Since majority of the tumors were based in the skull and because the tumors moved minimally during the operation, the use of the template was relatively easy. However, designing the preplan with the TPS was difficult, and template-making was time-consuming. Moreover, there was no needle-depth information.
Our preliminary study describes the advantages of Prowess TPS and 3D-printed template guided brachytherapy. Prowess TPS has a Stereo-Seed plan option and can support the design of any angle of needles and dose calculation, and can also design the printed template conformed to the body surface. Each patient has an individually designed template, with a preoperative TPS-designed needle puncture path. The paths contain the information regarding needle location, angle, number, and depth. These make the operation easier for physicians with less experience. The template can be easily fixed because its shape conforms to the patient's body surface. All the needles can be punctured into the correct positions, avoiding OARs while meeting dose requirements at the same time. The implanted seed position is in accordance with the preoperative plan, and the dose is consistent with the preoperative planning. In this study, all patients successfully underwent brachytherapy, where the number and location of the implanted seeds was in accordance with the preoperative planning requirements. The index, V90, V100, V150, and D90 of the postoperative plan was not statistically different from the preoperative plan, achieving good results.
Dose distribution in postplan according to preplan is essential. Adequate prostate seed implantation should match the conditions of D90 >90% and V100 >80%. Zelefsky et al. associated D90 <130 Gy (90% prescription dose) with a higher prostate-specific antigen relapse rate. If the D90 ≤110 Gy (75%) and V100 ≤75%, the case requires reimplantation. In our previous study, implanted seeds without template showed low dose consistency. The mean postoperative D90 was <88% of that in preplan. In addition, there was a bigger error, more than 30 Gy, in some cases which required reimplantation. Another study showed that the satisfactory rate of seed implantation was only 39%. The dose was not adequate according to the standard mentioned above. However, with 3D-printed template, the dose consistency can be improved greatly. Previous reports have shown a good dose consistency guided by 3D-printed template. The mean D90 in pre- and post-plan were 76.84 Gy versus 75.31 Gy and 137.61 Gy vs. 127.98 Gy, as reported by Zhang et al. and Wang et al., In this study, 14 (100%) out of 14 implanted doses were adequate. This is because all the needles can be inserted into the tumor easily according to preplan under the guidance of 3D-printed template.
Challenges to the broader use of 3D-printed template include perfect preplan designing, accurate template calibration, and physician's confidence in performing the procedures. The 3D-printed template is helpful in very difficult cases, including tumors that are adjacent to OARs, behind the bones, or close to the important blood vessels. Using 3D-printed template increases the preparation time, although the needle can be inserted into the tumor more quickly and accurately, resulting in potentially better dose consistency.
Although 3D-printed template guided seed brachytherapy has many advantages, there are still some hindrances. When the puncture path is too long, it results in deviation of needle position and causes errors in dose. In order to avoid this deviation, intraoperative real-time planning is performed after all the needles have been inserted, which will be based on the actual needle track, to re-plan the seed locations and ensure the dose distribution meets the preoperative plan requirements.
The limitations of this study include the fact that all patients were treated at a single clinic, without longtime follow-up and the clinical therapeutic outcomes. Moreover, the tumors were not in the same region. Therefore, the next step of our study will focus on multicenter research on tumors in the same region and observation of the therapeutic result. If the outcomes are considerably better than those of traditional free-hand operations, 3D-printed template guided brachytherapy might become a standard procedure.
Within the constraints that the location of the tumor is not deep and that it is in a relatively fixed position, 3D-printed template-guided seed brachytherapy is an appealing treatment method. The technique can provide accurate dose-distribution of radioactive seeds, with sufficient match between postoperative verification plan and preoperative planning requirements. However, for some tumors, it will not be easy to apply this technique as greater mobility is involved. This situation might change if further research is conducted in this field.
The authors would like to thanks Health and Family Planning Commission of Hebei province for supporting Juan Wang that allowed her to perform this study. We would like to thank the team at the nuclear department of Hebei General Hospital for their assistance in this study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6]
[Table 1], [Table 2]