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ORIGINAL ARTICLE
Year : 2018  |  Volume : 14  |  Issue : 12  |  Page : 1163-1169

Concurrent computed tomography-guided radioactive iodine-125 seeds percutaneous interstitial implantation and chemotherapy for treatment of cervical lymph node metastases


1 Department of Radiology, People's Hospital of LinZi District, Affiliated to Binzhou Medical College, Zibo, China
2 Department of Nuclear Medicine, People's Hospital of LinZi District, Affiliated to Binzhou Medical College, Zibo, China
3 Department of Oncology, People's Hospital of LinZi District, Affiliated to Binzhou Medical College, Zibo, China
4 Department of Urinary Surgery, People's Hospital of LinZi District, Affiliated to Binzhou Medical College, Zibo, China
5 Department of Neurology, People's Hospital of LinZi District, Affiliated to Binzhou Medical College, Zibo, China

Date of Web Publication11-Dec-2018

Correspondence Address:
Xiangjie Qi
Department of Urinary Surgery, People's Hospital of LinZi District, Affiliated to Binzhou Medical College, Zibo 255400
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-1482.202896

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 > Abstract 


Aim: The study aimed to evaluate the effect of concurrent computed tomography (CT)-guided percutaneous interstitial implantation of iodine-125 (125I) seeds and chemotherapy on cervical lymph nodes metastasis.
Methods: The prospective randomized study included 82 cases with cervical lymph nodes metastasis who were admitted to our hospital from January 2010 to June 2012. All the subjects were randomly divided into the concurrent 125I implantation and chemotherapy group (n = 48) and chemotherapy-only group (n = 34) according to the treatment strategy. The concurrent 125I implantation and chemotherapy group was treated with CT-guided 125I seeds implantation and routine chemotherapy. The routine chemotherapy included paclitaxel and cisplatin. Patients were followed up for 6 months.
Results: In the concurrent 125I implantation and chemotherapy group, overall response rate (complete response [CR] + partial response [PR]) was 82.61% and 85.51% at 2 and 6 months posttreatment, respectively. The longest diameter of CR and PR lymph nodes was markedly decreased after treatment (P < 0.05). In the chemotherapy-only group, overall response rate was 22.45% and 10.20% at 2 and 6 months posttreatment, respectively. The number of patients with moderate to severe pain was much less in concurrent 125I implantation and chemotherapy group than that of chemotherapy-only group (4.17% vs. 17.64%; P < 0.05) at 6-month posttreatment. No treatment-related death or severe complication was reported in the two groups.
Conclusion: Concurrent CT-guided 125I seeds implantation and chemotherapy is superior to routine chemotherapy in efficacy, safety, and pain relief in patients with cervical lymph nodes metastasis.

Keywords: Cervical lymph nodes metastasis, chemotherapy, computed tomography, iodine-125 seeds implantation, treatment planning system


How to cite this article:
Li Z, Wang X, Fang K, Shi J, Qi X, Sun R. Concurrent computed tomography-guided radioactive iodine-125 seeds percutaneous interstitial implantation and chemotherapy for treatment of cervical lymph node metastases. J Can Res Ther 2018;14, Suppl S5:1163-9

How to cite this URL:
Li Z, Wang X, Fang K, Shi J, Qi X, Sun R. Concurrent computed tomography-guided radioactive iodine-125 seeds percutaneous interstitial implantation and chemotherapy for treatment of cervical lymph node metastases. J Can Res Ther [serial online] 2018 [cited 2019 Sep 15];14:1163-9. Available from: http://www.cancerjournal.net/text.asp?2018/14/12/1163/202896




 > Introduction Top


Iodine-125 (125I) is a radioisotope of iodine with a half-life of 59.6 day and radiation energies ranged from 27 to 35 keV.[1] It has been used in various fields, such as biological assay and radiation therapy.[2],[3] 125I seeds implanted into the tumor emit low dose of X-rays and gamma rays, delivering a high and steady radiation to the tumor cells, but a lower radiation to nearby normal tissue.[4] In addition, its radiobiological advantage lies in its low and continuous release, which helps spare for adjacent normal tissue and reduces the risk of radiation exposure for medical stuff.[5] Therefore,125I is increasingly recognized as a feasible radiation source to implant permanently into the tumor. Computed tomography (CT)-guided implantation of 125I-labelled seeds has been proved to be a safe and feasible method for treatment of several types of tumors, such as recurrent rectal carcinoma,[6] pancreatic cancer,[7] nonsmall cell lung cancer,[8] and malignant thoracic tumors.[9]

The cervical region is characterized by rich lymphoid tissue. Cervical lymph node metastasis is often caused by head and neck malignancy and tumors at other sites, making complete removal of tumor a difficult task.[10] When metastatic cervical lymph nodes are determined, primary tumors often have progressed to an advanced grade.[11] Chemotherapy and radiation therapy are two routine options of treatment. However, they may cause several complications such as tissue fibrosis and vascular occlusion, which may severely affect the life quality of patients.[12],[13] Therefore, there is in need of a novel effective treatment modality. Wang et al.[14] have provided evidence that retroperitoneal metastatic lymph nodes can also be treated using CT-guided radioactive 125I seeds implantation, with the achievement of good pain relief. It leads us to test whether CT-guided 125I seeds implantation is feasible and safe for cervical lymph nodes metastasis. In the prospective randomized study, we compared concurrent 125I seeds implantation under CT guidance and chemotherapy and chemotherapy-only for the therapeutic effects on patients with cervical lymph nodes metastasis. The study would shed new light on application of CT-guided 125I seeds implantation in clinical practice.


 > Methods Top


Patients

This study included 82 patients with metastatic cervical lymph nodes metastasis in people's hospital of Linzi district of Zibo city, Shandong province, China, from January 2010 to June 2012. The patients met all the inclusion criteria: a history of histologically proven primary malignant tumor; 1–3 metastatic lymph nodes confirmed by biopsy; metastatic lymph nodes were shown by CT scanner (Siemens Somatom Definition 64, China) or magnetic resonance imaging (Siemens Symphony 1.5T, China) or positron emission tomography-CT (Discovery ST 16, USA); expected survival >6 months; absence of abnormal blood coagulation and platelet ≥100 × 1012/L; function of heart, lung, and other important organs within normal range. Exclusion criteria were: severe heart, lung, liver, and renal insufficiency; serious blood coagulation function disorder; uncontrolled serious cervical infection; poor general condition or cachexia.

Of these patients, 44 were male, and 38 were female. A total of 118 metastatic cervical lymph nodes were detected. Of these patients, 16 had primary nasopharyngeal carcinoma, 18 had primary esophageal carcinoma, 11 had primary tongue carcinoma, 10 had primary laryngeal cancer, 10 had primary breast cancer, 9 had lung cancer, 5 had gingival carcinoma, and 5 had thyroid carcinoma. The 82 patients were randomly divided into two groups through random numbers generated by computer: the concurrent 125I implantation and chemotherapy group (n = 48) and the chemotherapy-only group (n = 34). Patients' characteristics of the two groups are shown in [Table 1]. The two groups were not significantly different in age, gender, pain scores, and diameter of metastatic lymph nodes. The study protocol was approved by the Local Ethics Committee. All patients were informed of the treatment methods and provided written informed consent before the study.
Table 1: Characteristics of patients in two groups before treatment

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Instruments and computed tomography-guided iodine-125 seeds implantation procedure

The 125I seeds were purchased from the China Institute of Atomic Energy (Beijing, China), which were 4.5 mm in length and 0.8 mm in diameter.125I produces gamma rays (27.4–35.5 keV) with a half-life of 59.6 days, activities of 0.6–0.8 mCi, and penetration of 1.7 cm.

All patients in the concurrent 125I implantation and chemotherapy group were scanned on a 64-row CT scanner (LightSpeed VCT, GE Healthcare, USA) for cervical imaging with a slice thickness of 5 mm. The CT images were imported to the TPS System (Model HGGR-2000, Hokai Medical Instruments, Zhuhai, China). The gross tumor volume and the expected number of implanted 125I seeds were calculated automatically by TPS. The primary planning goal was defined as adequate planning target volume coverage (V90 >90%) with the prescribed dose.

After fasting 2 h, the patients received short-acting tramadol injection for sedation. They were placed in the proper position. Before the implantation, 0.1% lidocaine injection was used for local anesthesia. Under CT guidance,125I seeds were implanted into the cervical metastatic lymph nodes using 18-gauge needles (Hakko, Tokyo, Japan) at a spacing of 1 cm [Figure 1]. Repeated CT facilitated adjustment of depth and angle of needle. Special attention was paid to avoid injuring nearby main vessels, nerves, and organs. After the treatment, the puncture site was bandaged. If necessary, the surface of the bandaged site was compressed for hemostasis.
Figure 1: Computed tomography-guided iodine-125 seeds implantation procedure

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Postimplant management

After implantation, the patients were given 1U hemocoagulase intramuscularly at intervals of 6–8 h and 40 mg of methylprednisolone daily for 3 days. External-beam radiation therapy was generally suggested for the tolerable and agreeable patients without previous sessions or complications. Short-acting tramadol injection was preferred for painful patients after implantation.

Chemotherapy treatment

Patients in the concurrent 125I implantation and chemotherapy group and the chemotherapy-only group received routine chemotherapy according to the National Comprehensive Cancer Network guidelines. The chemotherapy included paclitaxel (135 mg/m2) on day 1 and cisplatin (35 mg/m2) on days 1–3. The treatment cycles were repeated every 3 weeks.

Follow-up and evaluation of curative effect

Follow-up CT scan was carried out at 2 and 6 months after intervention, respectively, for patients of the two groups. The efficacy was evaluated following the guidelines to evaluate the response to treatment in solid tumors.[15] Briefly, complete response (CR) was defined as the complete disappearance of all target lesions for longer than 1 month. Partial response (PR) was defined that the sum of the longest diameter of target lesions was decreased by >30% and then remained unchanged for longer than 1 month. Progressive disease (PD) referred to more than 20% increase in the sum of the longest diameter of target lesions or appearance of new lesion. Stable disease (SD) referred to the condition of all target lesions between SD and PD. CR and PR were defined as the total response rate.

Complications

The radiation adverse effects were determined based on the Toxicity Criteria of the Radiation Therapy Oncology Group and the European Organization for Research and Treatment of Cancer.[16],[17] Postimplant pain was evaluated using numeric rating scale (NRS) for pain, which recorded pain from level 0 (no pain) to level 10 (the worst possible pain).[18],[19] Pain score >3 on NRS suggested moderate to severe pain.[20]

Statistical analysis

Statistical analysis was carried out using SPSS software version 16.0 (Statistical Product and Service Solutions, Chicago, IL, USA). Quantitative data between two groups were compared using Student's t-test. Categorical data between groups were compared using Chi-square test, Fisher's exact test, or continuity correction test if appropriate. The median survival time was evaluated using the Wilcoxon test and Kaplan–Meier methods.


 > Results Top


Clinical outcome

For the concurrent 125I implantation and chemotherapy group (n = 48), at posttreatment 2 months [Table 2], follow-up CT scan revealed that, of the 69 cervical metastatic lymph nodes, CR was achieved in 40 cases, PR in 17 cases, SD in 10 cases, and PD in 2 cases. The response rate (sum of CR and PR) was 82.61%. The follow-up CT scan was conducted at 6 months again after treatment. As shown in [Table 3], 48 cases had CR, 11 cases had PR, 7 cases had SD, and 3 cases had PD with an overall response rate of 85.51%. Moreover, the overall response rate was not significantly different among different types of primary tumors at 2 and 6 months posttreatment (P > 0.05).
Table 2: Efficacy results of the concurrent iodine-125 implantation and chemotherapy group at 2-month posttreatment

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Table 3: Efficacy results of the concurrent iodine-125 implantation and chemotherapy group at 6-month posttreatment

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The chemotherapy-only group (n = 34) had a total of 49 metastatic cervical lymph nodes. The 2-month CT scan identified CR in 4 cases, PR in 7 cases, SD in 30 cases, and PD in 8 cases [Table 4]. The overall response rate was 22.45%. At 6-month posttreatment, CR was found in 2 cases, PR in 3 cases, SD in 18 cases, and PD in 20 cases with an overall rate of 10.20% [Table 5].
Table 4: Efficacy results of the chemotherapy-only group at 2-month posttreatment

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Table 5: Efficacy results of the chemotherapy-only group at 6-month posttreatment

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Evaluation of the longest diameter of target lesions

In the concurrent 125I implantation and chemotherapy group, CR and PR were found in 57 lymph nodes at 2 months after treatment. The longest diameter of the lymph node in CR and PR patients was 21.75 ± 0.51 mm before treatment and significantly decreased to 3.70 ± 0.78 mm at 2 months after treatment (P < 0.001). With regard to the remaining 12 lymph nodes with SD or PD, the pretreatment longest diameter (25.92 ± 2.14 mm) of target lesions was not significantly different from the longest diameter of target lesions at posttreatment 2 months (25.83 ± 2.00 mm, P > 0.05) [Figure 2]a. At 6-month posttreatment, the number of lymph nodes with CR or PR increased to 59. [Figure 2]b shows that the longest diameter of the 59 lymph nodes was significantly decreased at 6-month posttreatment compared to the pretreatment longest diameter (1.51 ± 0.45 mm vs. 21.78 ± 0.53 mm; P < 0.001). The longest diameter of the remaining 10 lymph nodes with SD or PD was not significantly different between pretreatment and 6-month posttreatment (27.40 ± 2.17 mm vs. 28.70 ± 3.24 mm; P > 0.05).
Figure 2: Changes in the longest diameter of lymph nodes before and after treatment in the concurrent iodine-125 seeds implantation and chemotherapy group (a and b) and routine chemotherapy group (c and d). **P < 0.01, ***P < 0.001

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In the chemotherapy-only group, CR or PR was found in 11 lymph nodes at 2-month posttreatment. The longest diameter was 26.91 ± 1.71 mm before treatment and significantly reduced to 12.00 ± 2.98 mm at 2-month posttreatment (P < 0.001). The remaining 38 lymph nodes with SD or PD were not significantly different in the longest diameter between 6-month posttreatment and pretreatment (22.79 ± 0.83 mm vs. 24.03 ± 0.66 mm; P > 0.05) [Figure 2]c. At 6 months after chemotherapy, there were five nodes with CR or PR. The longest diameter of five nodes significantly decreased at 6 months after treatment compared to pretreatment (11.20 ± 3.68 mm vs. 26.40 ± 3.37 mm; P < 0.01). On the contrary, the longest diameter of the 44 lymph nodes with SD or PD was markedly increased compared to that before treatment (30.45 ± 0.87 mm; 24.48 ± 0.64 mm; P < 0.001) [Figure 2]d.

Complications

Patients of the two groups were followed up for 6 months. As far as the concurrent 125I implantation and chemotherapy group concerned, no death or vascular thromboses were occurred. Topical skin swelling was reported in the first month in eight patients and evaluated as Grade 2 acute radiation skin reactions. Ten patients had mild to moderate pigmentation, which were scored as Grade 1 acute radiation skin reactions. Mild pain occurred in other patients, which was relieved after appropriate management. No spinal cord injury, laryngeal edema, and other complications were found in any patient. The concurrent 125I implantation and chemotherapy group and the chemotherapy-only group were not significantly different in other complications such as gastrointestinal toxicity and bone marrow toxicity.

Analysis of pain score

As shown in [Table 6], the number of patients with moderate to severe pain (pain score >3) in both the concurrent 125I implantation and chemotherapy group and the chemotherapy-only group obviously decreased at 2-month posttreatment (P < 0.01) and 6-month posttreatment compared to pretreatment (P < 0.001). Specifically, the pretreatment percentage of patients with moderate to severe pain was not significantly different between the two groups (P > 0.05). At 2- and 6-month posttreatment, the percentages of patients with moderate to severe pain were much lower in the concurrent 125I implantation and chemotherapy group compared to that in the chemotherapy group (P < 0.05).
Table 6: Pain syndromes of patients in the two groups before and after treatment

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 > Discussion Top


Percutaneous image-guided 125I seeds implantation has attracted increasing attentions because of its ability to deliver a high radiation dose to target lesions but spare nearby normal tissue.[21],[22] The study evaluated the clinical efficacy of CT-guided percutaneous 125I seeds implantation and routine chemotherapy in treating patients with cervical lymph nodes metastasis. These metastatic cervical lymph nodes were resulted from ten types of primary tumors, including primary nasopharyngeal carcinoma, primary esophageal carcinoma, primary tongue carcinoma, primary laryngeal cancer, primary breast cancer, primary lung cancer, primary gingival carcinoma, and primary thyroid carcinoma. Findings of this study suggest that concurrent 125I implantation and chemotherapy is a safe and effective option of treatment for patients with cervical lymph nodes metastasis.

The previous studies have unveiled that CT-guided 125I seeds implantation is a safe and useful interventional treatment option for retroperitoneal lymph node metastases[14],[23] and mediastinal metastatic lymph nodes recurrence from esophageal carcinoma.[24] In a retrospective study, Jiang et al.[25] have also suggested the feasibility of this treatment modality for patients with recurrent head and neck cancers. Moreover, Huang et al.[26] have reported that 125I seeds embedding under CT guidance is a safe and feasible method for treating head and neck cancer patients with unmanageable cervical lymph node metastases, as evidenced by the findings that the overall survival rates at 3 months, 6 months, 1 and 2 years were 100%, 100%, 67.74% and 45.16%, separately. Compared with the study of Huang et al.,[26] the present study included cervical lymph node metastases from ten types of primary tumors: primary nasopharyngeal carcinoma, primary esophageal carcinoma, primary tongue carcinoma, primary laryngeal cancer, primary breast cancer, primary lung cancer, primary gingival carcinoma, and primary thyroid carcinoma. No treatment-related death was found in the 6-month follow-up after the concurrent percutaneous 125I seeds implantation and chemotherapy, which is in concordance with Huang's study. Moreover, the study found that for patients receiving concurrent CT-guided percutaneous 125I seeds implantation and chemotherapy, the overall response rate was 82.61% at 2-month posttreatment and 85.51% at 6-month posttreatment, which were similar to the results of Wang et al.[14] Moreover, in the current study, the longest diameter of lymph nodes with CR and PR was markedly reduced after concurrent percutaneous 125I implantation and chemotherapy. In sharp contrast, the overall response rate of patients receiving chemotherapy only was 22.45% and 10.20% at 2- and 6-month posttreatment, respectively. In addition, cervical lymph node metastases of different types of primary tumors were not significantly different in the posttreatment overall response rate, indicating that the efficacy of concurrent CT-guided 125I seeds implantation and chemotherapy is not associated with the type of primary tumor. These findings suggest that concurrent CT-guided 125I seeds implantation and chemotherapy was more effective than routine chemotherapy only in treating cervical lymph node metastases.

The study of Peponi et al.[27] has suggested that reradiation is related to poor prognosis in patients with recurrent head and neck cancer with an incidence of 20% of grade 3 acute toxicity and incidence of 23% of Grade 3–4 late radiation-induced complications. Duprez al.[28] have found that although intensity-modulated radiotherapy could provide 5-year overall survival for 25% of patients with recurrent head and neck cancer, it leads to severe late toxicity in 66% of patients. In this study, Grade 2 acute radiation skin reaction occurred in eight patients and Grade 1 acute radiation skin reactions occurred in ten patients. No other severe complications or treatment-related death was reported. These observations were in support of the security of concurrent CT-guided percutaneous 125I seeds implantation and chemotherapy for patients with cervical metastatic lymph nodes.

Patients with cervical metastatic lymph nodes often suffer from pain, which might be related to compression of nerve fibers or cervical plexus invasion.[29],[30] In the current study, the concurrent CT-guided 125I seeds implantation and chemotherapy appeared to achieve a significant pain relief effect, as indicated by the finding that the proportion of patients with moderate to severe pain was remarkably decreased at 6 month postimplant (6 months posttreatment, 4.17%; pretreatment, 35.41%). Moreover, the concurrent 125I seeds implantation and chemotherapy group had an obviously lower percentage of patients with moderate to severe pain than the routine chemotherapy-only group (17.64%) at 6-month posttreatment. It reveals that concurrent 125I seeds implantation and chemotherapy is superior to the routine chemotherapy in regard to pain relief.

The study has some limitations. The sample size is limited for each primary tumor type. The follow-up only has 6 months. Moreover, clinical benefit responses were not involved in the study. Further studies with a longer follow-up and a larger population are necessary in the process to verify the findings of this study.


 > Conclusion Top


This study suggests that concurrent CT-guided 125I seeds implantation and chemotherapy is more effective and safer than routine chemotherapy-only for treating cervical lymph nodes metastasis. Concurrent CT-guided 125I seeds implantation and chemotherapy also shows better palliative pain relief than routine chemotherapy. Long-term studies are warranted to validate the findings of our study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6]



 

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