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ORIGINAL ARTICLE
Year : 2020  |  Volume : 16  |  Issue : 2  |  Page : 372-378

Feasibility and clinical value of computed tomography-guided125I brachytherapy for pain palliation in patients with retroperitoneal lymph node metastases


1 Department of Interventional Oncology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences; The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
2 Department of Interventional Oncology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China

Date of Submission14-Aug-2019
Date of Decision29-Oct-2019
Date of Acceptance05-Feb-2020
Date of Web Publication28-May-2020

Correspondence Address:
Xiaoming Chen
Department of Interventional Oncology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences; The Second School of Clinical Medicine, Southern Medical University, Guangzhou
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_597_19

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 > Abstract 


Aims: The aim was to evaluate the feasibility and clinical value of computed tomography (CT)-guided125 I brachytherapy for pain palliation in patients with retroperitoneal lymph node metastases.
Materials and Methods: A total of 23 patients with retroperitoneal lymph node metastases and those who had moderate-to-severe pain from January 2014 to December 2018 were enrolled in the study. The primary tumors included pancreatic (n = 12), gastric (n = 4), hepatocellular (n = 4), colorectal (n = 2), and esophageal carcinomas (n= 1). Patients were treated with CT-guided percutaneous125 I brachytherapy during the study. The Brief Pain Inventory-Short Form was used to record and compare pain intensity and interference by pain. Treatment-related complications were also evaluated according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Criteria. Statistical analysis was performed using SPSS software version 22.0
Results: The primary success rate of125 I seed implantation was 95.7% (22 of the 23 patients). As pain evolved, the patients achieved obvious pain palliation ratings for “worst pain” and “average pain” at 72 h and 4 weeks after brachytherapy, respectively, whereas “pain right now” at 12 weeks was significantly relieved after brachytherapy. No serious complications developed during the perioperative period.
Conclusions: In the treatment of intractable carcinomatous pain in patients with retroperitoneal lymph node metastases, CT-guided125 I brachytherapy is a feasible and effective modality for pain palliation.

Keywords: Brachytherapy, pain palliation, retroperitoneal lymph node metastases


How to cite this article:
Mai Q, Mo Z, He J, Chen M, Gou Q, Shi F, Chen X. Feasibility and clinical value of computed tomography-guided125I brachytherapy for pain palliation in patients with retroperitoneal lymph node metastases. J Can Res Ther 2020;16:372-8

How to cite this URL:
Mai Q, Mo Z, He J, Chen M, Gou Q, Shi F, Chen X. Feasibility and clinical value of computed tomography-guided125I brachytherapy for pain palliation in patients with retroperitoneal lymph node metastases. J Can Res Ther [serial online] 2020 [cited 2020 Jul 16];16:372-8. Available from: http://www.cancerjournal.net/text.asp?2020/16/2/372/285192




 > Introduction Top


Abdominal malignancies usually lead to retroperitoneal lymph node metastases. Although retroperitoneal lymph node metastases did not directly increase mortality, approximately 10%–25% of patients with retroperitoneal lymph node metastases develop severe carcinomatous pain.[1],[2] Some patients with retroperitoneal lymph node metastases did not improve following systemic treatments, such as chemotherapy, molecularly targeted therapy, and immunotherapy.[1],[3],[4] Previous studies have shown that such systemic treatments can result in limited, long-term pain palliation.[5] Therefore, high-dose analgesic drugs have been used to control pain. However, side effects and costs limit the use of this type of treatment. Therefore, alternative treatments are needed.

125 I brachytherapy has been confirmed to have benefits in lesion control and symptom relief in patients with solid tumors.[1],[6] Thus, it could be an optional future treatment for patients after systemic treatment failure. Unfortunately, few reports have evaluated the clinical value of125 I brachytherapy in patients with retroperitoneal lymph node metastases. This study aimed to evaluate the feasibility and clinical value of computed tomography (CT)-guided125 I brachytherapy for pain palliation in patients with retroperitoneal lymph node metastases.


 > Materials and Methods Top


In this retrospective study, all patients with retroperitoneal lymph node metastases had moderate-to-severe pain. The average pain intensity before brachytherapy is shown in [Table 1]. All enrolled patients accepted systemic treatments, which failed to satisfactorily control their pain. The Ethics Committee of the Guangdong Provincial People's Hospital approved our study.
Table 1: Scores of pain at different times

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The inclusion criteria were as follows: (a) clinical or histological diagnosis of retroperitoneal lymph node metastases; (b) pain relief failure following systemic treatments, such as chemotherapy, molecularly targeted therapy, and immunotherapy; (c) retroperitoneal lymph node metastases as the only possible cause of pain; (d) scores of at least four points on the “worst pain” item of the Brief Pain Inventory (BPI) 24 h prior to filling out the inventory; (e) Karnofsky Performance Status score ≥70; (f) absence of severe coagulation disorders (prothrombin activity <40% or platelet count <75 × 109/L); and (g) unsuitability for radiation therapy as determined by a radiation oncologist.

125 I seeds

The radioactive125 I seeds (Yunke Pharmaceutical Limited Liability Company, Chengdu, China) consisted of cylindrical titanium packages measuring 0.8 mm in diameter and 4.5 mm in length. The central source of the particles was a125 I radionuclide silver rod with a diameter of 0.5 mm and a length of 3.0 mm. The matched peripheral dose (MPD) was 100–140 Gy, the average energy was 27–35 KeV, and the radius of effective antitumor activity was 1.7 cm. Each seed had an initial activity of 0.8 mCi and a half-life of 59.6 days; 93%–97% of the brachytherapy dose was delivered within 8–10 months.

125 I brachytherapy

Before125 I seed implantation, 5- and 1-mm-thick CT sections were obtained in all patients. A computerized treatment planning system (TPS) (BT-RSI, Beijing Atom and High Technique Industries, Beijing, China) was used to create a treatment plan for each patient. The gross tumor volume (GTV), planned target volume (PTV), and surrounding vital organs were carefully delineated in each CT slice. The PTV was defined as an extension measuring 0.5 cm around the GTV. Based on three orthogonal diameters within the targeted tumor site and a prescribed MPD, the TPS calculated the position of the brachytherapy applicator and number of seeds to be implanted [Figure 1], after which it generated a dose–volume histogram, including the isodose curves of different targets. The prescribed dose of the planned target was an average of 120 Gy (range, 100–150 Gy).[7] The dose received by the surrounding organs was based on normal tissue constraint guidelines. The PTV edge accounted for 70%–90% of the isodose curve; thus, 95% of the prescribed dose covered the PTV. On the day of the procedure, the patients were positioned on the CT gantry and evaluated to locate the lesion site(s). Several 5-mm axial slices were obtained to delineate the upper and lower borders of the tumors. After inducing anesthesia with local infiltration of 5–15 mL of 1% lidocaine (Liduokayin, Yimin, Yichang, China), an 18G spinal needle (Yunke Pharmaceutical) was inserted into the farthest tumor edge and placed approximately ≤5 mm from its border. Then, a clip implant gun (Yunke Pharmaceutical) was attached to the applicator for implantation. The125 I seeds were released from the deep to shallow area while retracting the needle and keeping the adjacent125 I seeds at a distance of 5–15 mm. CT was performed after completion to identify any postprocedural complications and verify that the position and intensity of the125 I seeds were in accordance with the TPS. If the lesion showed insufficient radioactivity, the procedure was repeated, and additional125 I seeds were implanted. In our study, the actual dose to the lesion in these patients after125 I treatment was 122 ± 4.5 Gy.
Figure 1:125I brachytherapy treatment plan for retroperitoneal lymph node metastases. (a) Computed tomography images of the lesion were reconstructed using a computerized treatment planning system, and the position of the brachytherapy applicators was calculated. (b) Three-dimensional image showing the relationship between the positions of the applicators, lesions, and spinal cord. (c) Two-dimensional image showing the irradiation dose (red area) of the125I brachytherapy field. (d) Dose–volume histogram indicating the prescribed dose to the lesion received

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Follow-up and evaluation criteria

A BPI-Short Form (SF) (a validated visual analog scale with scores ranging from 0 to 10) was completed by each patient to obtain a measure of pain intensity (“worst pain,” “least pain,” “average pain,” and “pain right now”) and pain interference (with the seven health-related quality-of-life dimensions of general activity, mood, walking ability, normal work, relations with others, sleep, and enjoyment of life).[8] The patients completed the BPI-SF with assistance from a study coordinator who was familiar with focal painful metastases. The BPI-SF was administered before the procedure and after 24 h, 72 h, 4 weeks, and 12 weeks. All patients underwent dynamic contrast-enhanced CT and clinical hematological examinations within 3–5 weeks after the procedure to evaluate the safety and efficacy of the therapy. The percentages of intra- and post-procedural complications were recorded according to the Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer Late Radiation Morbidity Scoring Criteria.[9]

Statistical analysis

Statistical analyses were performed using SPSS statistical software version 22.0 (International Business Machines, New York, USA). Values were presented as means ± standard deviations. Patient-assessed BPI-SF scores were analyzed using one-way analysis of variance. Statistical significance was set at P < 0.05.


 > Results Top


Patient characteristics

Our retrospective study enrolled 23 patients with retroperitoneal lymph node metastases who had moderate-to-severe pain from January 2014 to December 2018. The patient characteristics are shown in [Table 2]. Chemotherapy, molecularly targeted therapy, and immunotherapy were defined as the systemic treatment modalities in this study. All patients failed to obtain satisfactory pain relief with the systemic treatment modalities.
Table 2: Patient characteristics

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In patients with pancreatic carcinoma, chemotherapy was thefirst-line treatment. Three patients (25%) received immunotherapy after chemotherapy failure. In patients with gastric and colonic carcinoma, chemotherapy was also thefirst-line treatment, and three of them (50%) received molecularly targeted therapy after chemotherapy failure. In patients with hepatocellular carcinoma, sorafenib therapy was thefirst-line treatment, and one patient received immunotherapy after sorafenib therapy failure. Patients with esophageal carcinoma received immunotherapy after chemotherapy failure. Oxycodone and fentanyl transdermal patches were administered to all patients as analgesic medications. The mean doses of oxycontin and fentanyl transdermal patches were 65.3 ± 20.8 mg/day (60–240 mg/day) and 12.41 mg/3 day (8.4–25.2 mg/3 days), respectively. Unfortunately, a high dose of oxycontin or fentanyl transdermal patch could not satisfactorily relieve pain in all patients in our study. We defined T0 as the preoperative time and T1, T2, T3, and T4 as 24 h, 72 h, 4 weeks, and 12 weeks after brachytherapy, respectively.

Preoperative (T0) pain evaluation

The mean BPI-SF scores of “worst pain,” “least pain,” “average pain,” and “pain right now” at T0 were 7.7 ± 1.4 (95% confidence interval [CI], 6.2–8.9), 3.4 ± 1.2 (95% CI, 2.5–4.7), 5.5 ± 0.9 (95% CI, 4.5–6.5), and 5.6 ± 0.7 (95% CI, 4.9–6.4), respectively [Figure 2].
Figure 2: Scores of pain at different times

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Pain evaluation 24 h after the procedure (T1)

Pain was relieved in 12 patients (52.1%) at T1. The BPI-SF scores of “worst pain,” “least pain,” “average pain,” and “pain right now” were 4.9 ± 1.3 (95% CI, 3.5–5.4), 2.2 ± 0.6 (95% CI, 1.5–3.1), 3.4 ± 0.8 (95% CI, 2.6–4.1), and 3.8 ± 0.6 (95% CI, 3.3–4.5), respectively. There was no significant difference between the T0 and T1 scores.

Pain evaluation 72 h after the procedure (T2)

Pain was relieved in 18 patients (78.2%) at T2, and the BPI-SF scores of “worst pain,” “least pain,” “average pain,” and “pain right now” were 3.3 ± 1.1 (95% CI, 2.4–4.1), 2.3 ± 0.4 (95% CI, 2.0–2.6), 2.5 ± 0.3 (95% CI, 2.3–2.8), and 3.1 ± 0.6 (95% CI, 2.4–3.9), respectively. The scores of “worst pain” and “average pain” were significantly higher than those of T0.

Pain evaluation 4 weeks after the procedure (T3)

Pain was relieved in 19 patients (82.6%) at T3, and the BPISF scores of “worst pain,” “least pain,” “average pain,” and “pain right now” were 3.5 ± 0.9 (95% CI, 2.6–4.3), 2.5 ± 0.3 (95% CI, 2.0–3.2), 2.8 ± 0.5(95% CI, 2.2–3.6), and 2.5 ± 0.5 (95% CI, 1.7–3.3), respectively. The scores of “worst pain” and “average pain” were also significantly higher than those at T0.

Pain evaluation 12 weeks after the procedure (T4)

Pain was relieved in 14 patients (60.9%) at T4, and the BPISF scores of “worst pain,” “least pain,” “average pain,” and “pain right now” were 4.1 ± 1.0 (95% CI, 2.6–5.3), 2.1 ± 0.7 (95% CI, 1.2–3.4), 3.1 ± 0.4 (95% CI, 2.4– 3.9), and 2.5 ± 0.7 (95% CI, 1.5–3.4), respectively. Only the score of “pain right now” was significantly higher than that at T0.

Pain interference evaluation before and after the procedure (with the seven health-related quality-of-life dimensions of general activity, mood, walking ability, normal work, relations with other people, sleep, and enjoyment of life)

The scores in the seven health-related quality-of-life dimensions from the BPI-SF are shown in [Table 3]. No health-related quality-of-life dimension scores were different between T1/T2 and T0. At T3 and T4, the scores in mood, walking ability, and sleep were significantly different compared to those at T0. Moreover, the score of general activity at T4 [Figure 3] was significantly lower than that at T0.
Table 3: Scores of health-related quality-of-life dimensions

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Figure 3: Scores of health-related quality-of-life dimensions

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Changes in the use of analgesic medications

Analgesic drug doses were evaluated during the follow-up period. Information on changes in the use of analgesic medications at T0 to T4 is shown in [Table 4]. The dose of analgesic drug was decreased in 12 patients at T2 and 18 patients (including patients whose doses were decreased at T2) at T3. As a result, the dose of analgesic drug was decreased in a total of twenty patients, and five patients required increased doses at T4.
Table 4: Information on changes in the use of analgesic medications

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Complications of treatment

As shown in [Table 5], the percentage of complications was 13.1% (3/23), which included bleeding (n = 2) and radiation enterocolitis (n = 1). All adverse events were of Grade 1–2. No serious complications developed during the perioperative period.
Table 5:125I brachytherapy-related complications (n=23)

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 > Discussion Top


Although metastatic retroperitoneal lymph nodes do not directly increase mortality,[1],[10],[11] pain is one of the main clinical symptoms and can interfere considerably with patients' daily activities.[12],[13],[14] Some patients with retroperitoneal lymph node metastases develop severe carcinomatous pain. Unfortunately, pain could not be satisfactorily relieved in all patients receiving systematic treatments. If systemic treatment fails or drug resistance develops, patients usually have pain recurrence, as systemic treatment does not provide long-term relief of pain caused by retroperitoneal lymph node metastases.[2],[15],[16] When pain intensifies, regional therapies are indicated. Because the aim of regional therapy is palliative, radiotherapy, a minimally invasive form of treatment, is preferred to surgical resection. External beam radiotherapy (EBRT) is thefirst-line radiotherapy technique in the treatment of retroperitoneal lymph node metastases.[13],[17] However, some limitations of EBRT can compromise pain palliation. First, the low precision of EBRT indicated that less-than-optimal doses must be administered when a metastatic lesion is adjacent to vital organs to prevent radiation injury. Although multiple fractions of EBRT, three-dimensional conformal radiotherapy, and intensity-modulated radiation therapy have been developed to achieve definitive radiotherapy, the inevitable risk of radiation injury significantly decreases patients' tolerance to such techniques.[18] Second, there is usually a delay between thefirst administration of EBRT and pain palliation.125 I seed implantation, an emerging radiotherapy technique, has been widely used to treat malignant solid tumors.125 I seeds continuously emit low doses of X- and γ-rays with a half-life of 59.6 days, providing a long-term cytocidal effect on tumor cells. In the process of125 I seed decay, the tumor tissue can receive radiation doses of 110–160 Gy. Moreover, these doses cover a target area diameter of 1.7 cm, thereafter, rapidly decreasing with increasing distance. Compared with EBRT, the main advantage of125 I seed radiation is derived from its enhanced conformality and rapid dose falloff, allowing it to deliver biologically higher doses to the tumor while simultaneously reducing the dose to adjacent normal structures at an extremely low rate.

In our study,125 I brachytherapy proved to be a feasible and effective modality for pain palliation caused by retroperitoneal lymph node metastases. The success rate of125 I brachytherapy implantation was 95.7% (22/23). Patients achieved significant relief from pain after brachytherapy, particularly those in “worst pain” and “average pain” categories. The results from our study showed that 12 weeks after125 I seed implantation, pain was still controlled satisfactorily. The score of health-related quality-of-life dimensions also decreased universally, particularly in “general activity” at T4 and “mood,” “walking ability,” and “sleep” at T3 and T4. In addition, the doses of analgesic medications were decreased significantly after125 I seed implantation, resulting in fewer side effects and lower cost. Consequently, pain interfered with patients' daily lives much more mildly.

Our study had some limitations, including a small sample size and single-arm study design. Moreover, the follow-up period was short, and larger sample sizes and longer follow-up studies are needed for further analyses. Moreover, it was difficult to manually puncture the retroperitoneal lymph nodes with the brachytherapy needles, which can decrease the accuracy of125 I seed implantation and increase the intensity of intraprocedural pain.


 > Conclusion Top


Therefore, as a minimally invasive method, CT-guided125 I brachytherapy is feasible and safe in the treatment of patients with retroperitoneal lymph node metastases and achievement of pain palliation, which could be a complementary and helpful treatment to improve patients' quality of life.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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Yao L, Jiang Y, Jiang P, Wang H, Meng N, Qu A, et al. CT-guided permanent125 I seed interstitial brachytherapy for recurrent retroperitoneal lymph node metastases after external beam radiotherapy. Brachytherapy 2015;14:662-9.  Back to cited text no. 1
    
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Wang Z, Lu J, Gong J, Zhang L, Xu Y, Song S, et al. CT-guided radioactive125I seed implantation therapy of symptomatic retroperitoneal lymph node metastases. Cardiovasc Intervent Radiol 2014;37:125-31.  Back to cited text no. 2
    
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Konstantinidis IT, Warshaw AL, Allen JN, Blaszkowsky LS, Castillo CF, Deshpande V, et al. Pancreatic ductal adenocarcinoma: Is there a survival difference for R1 resections versus locally advanced unresectable tumors? What is a “true” R0 resection? Ann Surg 2013;257:731-6.  Back to cited text no. 3
    
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Feng S, Wang L, Xiao Z, Maharjan R, Chuanxing L, Fujun Z, et al.125 I Seed Implant Brachytherapy for Painful Bone Metastases After Failure of External Beam Radiation Therapy. Medicine (Baltimore) 2015;94:e1253.  Back to cited text no. 6
    
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Horwitz EM, American Brachytherapy Society. ABS brachytherapy consensus guidelines. Brachytherapy 2012;11:4-5.  Back to cited text no. 7
    
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Cleeland CS, Ryan KM. Pain assessment: Global use of the Brief Pain Inventory. Ann Acad Med Singapore 1994;23:129-38.  Back to cited text no. 8
    
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Cox JD, Stetz J, Pajak TF. Toxicity criteria of the Radiation Therapy Oncology Group (RTOG) and the European Organization for Research and Treatment of Cancer (EORTC) Int J Radiat Oncol Biol Phys 1995;31:1341-6.  Back to cited text no. 9
    
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Lin L, Wang J, Jiang Y, Meng N, Tian S, Yang R, et al. Interstitial125 I Seed implantation for cervical lymph node recurrence after multimodal treatment of thoracic esophageal squamous cell carcinoma. Technol Cancer Res Treat 2015;14:201-7.  Back to cited text no. 10
    
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Cao Q, Wang H, Meng N, Jiang Y, Jiang P, Gao Y, et al. CT-guidance interstitial (125) Iodine seed brachytherapy as a salvage therapy for recurrent spinal primary tumors. Radiat Oncol 2014;9:301.  Back to cited text no. 12
    
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Andrade RS, Proctor JW, Slack R, Marlowe U, Ashby KR, Schenken LL. A simple and effective daily pain management method for patients receiving radiation therapy for painful bone metastases. Int J Radiat Oncol Biol Phys 2010;78:855-9.  Back to cited text no. 14
    
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Gao F, Li C, Gu Y, Huang J, Wu P. CT-guided 125I brachytherapy for mediastinal metastatic lymph nodes recurrence from esophageal carcinoma: Effectiveness and safety in 16 patients. Eur J Radiol 2013;82:e70-5.  Back to cited text no. 15
    
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Zhang FJ, Li CX, Zhang L, Wu PH, Jiao DC, Duan GF. Short- to mid-term evaluation of CT-guided125 I brachytherapy on intra-hepatic recurrent tumors and/or extra-hepatic metastases after liver transplantation for hepatocellular carcinoma. Cancer Biol Ther 2009;8:585-90.  Back to cited text no. 16
    
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Yeo CJ, Cameron JL, Lillemoe KD, Sohn TA, Campbell KA, Sauter PK, et al. Pancreaticoduodenectomy with or without distal gastrectomy and extended retroperitoneal lymphadenectomy for periampullary adenocarcinoma, part 2: Randomized controlled trial evaluating survival, morbidity, and mortality. Ann Surg 2002;236:355-66.  Back to cited text no. 17
    
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Zhao JX, Liang Y, Liu Z, Ke X, Li H, Zhang H, et al. 3d-printing template assisted125 I seed interstitial brachytherapy for retroperitoneal lymph node metastasis: Individual template design method. Brachytherapy 2018;17:S142.  Back to cited text no. 18
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]
 
 
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