|Year : 2019 | Volume
| Issue : 4 | Page : 807-812
Clinical efficacy of computed tomography-guided iodine-125 seed implantation therapy for patients with metastatic epidural spinal cord compression: A retrospective study
Yun Liu1, Chuang He2, Yang Li3, Yu-Xiao Chen2, Li Yang2, Ting-Yuan Li2, Liang-Shan Li2, Xue-Quan Huang2
1 Cancer Center, Institute of Surgery Research, Third Affiliated Hospital, The Army Medical University, Chongqing, China
2 Treatment Center of Minimally Invasive Intervention and Radioactive Particles, Southwest Hospital, The Army Medical University, Chongqing, China
3 Department of Radiology, PLA No. 452 Hospital, Chengdu, Sichuan Province, China
|Date of Web Publication||14-Aug-2019|
Treatment Center of Minimally Invasive Intervention and Radioactive Particles, Southwest Hospital, the Army Medical University, Chongqing 400038
Source of Support: None, Conflict of Interest: None
Background: This study evaluated the clinical efficacy of computed tomography (CT)-guided radioactive iodine-125 (125 I) seed implantation in patients with metastatic epidural spinal cord compression (MESCC).
Materials and Methods: A cohort of 22 patients with MESCC were retrospectively enrolled. All patients underwent CT-guided 125 I seed implantation therapy via standard procedures. Clinical indexes, including the University of Texas MD Anderson Cancer Center (MDA) criteria for tumor responses, numerical rating scale (NRS) for the degree of pain, Karnofsky Performance Status (KPS) for quality of life, American Spinal Injury Association (ASIA) impairment scale, grade of ESCC, and radiation dose, were evaluated and recorded pre- and post-operation. A follow-up evaluation was performed at least 3 months after the operation. Finally, pre- and post-operative differences in these clinical indexes were compared. Overall survival was recorded.
Results: Operations were successfully performed on all patients. A median of 48 (range, 7–103) seeds were implanted in lesions, and the postoperative target verified dose D90 was 11,072.4 ± 1773.5 cGy. Patients were followed for a median of 6 months (range, 3–38 months). The median survival time was 10 months; the response rate was 18/22 (82%); the local control rates at 3, 6, and 12 months were 91.3%, 81.9%, and 81.9%, respectively; and the survival rates were 80%, 50.0%, and 21.9% at 6, 12, and 18 months, respectively. The ESCC grade was significantly lower (P < 0.05). Based on the ASIA impairment scale, the nerve functional reservation, recovery, and decline rates were 63.7% (14/22), 27.3% (6/22), and 9% (2/22), respectively. The NRS and KPS were both significantly improved in the 3rd month of follow-up (P < 0.05).
Conclusion: CT-guided 125 I seed implantation represents an effective and safe palliative care for patients with MESCC, which can effectively relieve pain and spinal cord compression and improve nerve function and quality of life.
Keywords: Iodine-125 seed, brachytherapy, computed tomography guided, interstitial implantation, metastatic epidural spinal cord compression
|How to cite this article:|
Liu Y, He C, Li Y, Chen YX, Yang L, Li TY, Li LS, Huang XQ. Clinical efficacy of computed tomography-guided iodine-125 seed implantation therapy for patients with metastatic epidural spinal cord compression: A retrospective study. J Can Res Ther 2019;15:807-12
|How to cite this URL:|
Liu Y, He C, Li Y, Chen YX, Yang L, Li TY, Li LS, Huang XQ. Clinical efficacy of computed tomography-guided iodine-125 seed implantation therapy for patients with metastatic epidural spinal cord compression: A retrospective study. J Can Res Ther [serial online] 2019 [cited 2019 Nov 16];15:807-12. Available from: http://www.cancerjournal.net/text.asp?2019/15/4/807/264301
Yun Liu and Chuang He contributed equally to this paper
| > Introduction|| |
The spine is the most common involved site of bone metastasis, which occurs in 40% of all patients with cancer. Patients with spine metastasis often experience skeletal complications, such as cancer-induced bone pain, hypercalcemia, pathological bone fractures, and metastatic epidural spinal cord compression (MESCC), which significantly diminish their quality of life., MESCC is defined as cancer that metastasizes to the spine or epidural space and compresses the spinal cord. A recent population-based study revealed that >2/100,000 individuals among the general Chinese population may have suffered from MESCC in 2012. Magnetic resonance imaging (MRI) is the main method employed in the diagnosis of patients suspected of having MESCC.
The treatment of spinal metastases is mostly palliative, with the goals of pain relief, maintenance or recovery of neurologic function, local durable tumor control, and improved quality of life. Recently, efforts have been made to introduce the use of computed tomography (CT)-guided iodine-125 (125 I) seed implantation into the field of spine tumor treatment with encouraging results., This technique ensures a high radiation dose at the tumor while relatively sparing the overlying spine; however, few studies have focused on brachytherapy outcomes in patients with MESCC.
Therefore, in this study, we investigated the clinical value and safety of implanting 125 I radioactive seeds for the treatment of MESCC.
| > Materials and Methods|| |
From May 2011 to October 2015, 22 patients (36 spinal metastases) with MESCC were enrolled in this retrospective study. All patients had been reviewed by surgeons and radiation oncologists and were considered either unsuitable for another round of surgery and radiotherapy (RTx) or the patients had refused to receive surgery and RTx. All patients were diagnosed with MESCC based on imaging and histopathology examinations and received 125 I seed brachytherapy. Patient characteristics are shown in [Table 1]. Inclusion criteria were as follows: MESCC at any level confirmed by MRI, Karnofsky performance status (KPS) >60, estimated survival time of >3 months, and recurrence after surgery or RTx. Exclusion criteria were the following: KPS <60, an estimated survival time of <3 months, and any patient who refused to give written informed consent to participate in this study.
The study protocol followed guidelines for experimental investigation with human subjects in accordance with the Declaration of Helsinki and was approved by the ethics committee. Written informed consent was obtained from each patient before the study.
Iodine-125 seed implantation
All patients underwent CT scanning with spine imaging parameters of 120 kV, 200 mA, and a slice thickness of 5 mm.125 I seeds (Beijing ZHIBO Bio-Medical Technology Co., Ltd, China), each with a specific activity of 0.8 mCi, were used, along with a treatment planning system (TPS) (Image-Processing Center; Beihang University; Beijing). The gross tumor volume (GTV) was delineated on each section of the CT image by a radiologist. The planning target volume was defined as a 10–15 mm expansion that was external to the GTV. The matched peripheral dose for patients was 120 Gy. The route of puncture and number of implanted seeds were planned by the TPS.
The 125 I seed implantation was performed under adequate local anesthesia with patients in a prone position. The 18-Gauge implantation needles were inserted into the tumor at an interval of 1.0 cm in a parallel array; care was taken to avoid puncturing the nearby vessels and spinal cord. All 125 I seeds were implanted by 18-Gauge implantation needles, and the seeds were arranged in a straight line at 0.5–1 cm intervals. The minimal distance between seeds and spinal cord was 1.0 cm. Repeated CT scans were performed soon after the procedure to confirm the distribution of seeds, and the CT images were collected and input into the TPS [Figure 1].
|Figure 1: The computed tomography-guided iodine-125 brachytherapy and dose verification procedure after iodine-125 seed implantation in a hepatocellular carcinoma patient. (a) Both the position of the applicator and dose were calculated based on the treatment planning system before surgery. (b) Applicators were inserted into the tumor to implant iodine-125 seeds based on the treatment planning system. (c) Verification after iodine-125 brachytherapy. The planning target volume was covered by the isodose curve. (d) A dose-volume histogram of tumor and surrounding tissues for the treatment planning system. Green line represents target lesion and yellow line represents canalis vertebralis|
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After seed implantation, follow-up was performed by the hospital. The median follow-up was 6 months (range, 3–38 months) and included physical examinations, blood tests, and MRI at each follow-up or when any clinical symptom appeared. Tumor responses were assessed using the University of Texas MD Anderson Cancer Center (MDA) criteria, which divides responses into 4 standard categories (complete response [CR], partial response [PR], progressive disease [PD], and stable disease [SD]) and includes quantitative and qualitative assessments of bone metastases. The response rate after brachytherapy was defined as PR + CR. The grade of ESCC was estimated at the end of the follow-up period. Pain was evaluated using a numerical rating scale (NRS), and the quality of life of the patients was estimated by KPS before and 3 months after surgery. The American Spinal Injury Association (ASIA) grade was used to assess nerve function at the end of the follow-up period. To calculate survival, any deaths were scored as an event. Toxicity was evaluated according to the Radiation Therapy Oncology Group (RTOG) criteria. Surgery-related complications were diagnosed by either CT or laboratory examination.
The statistical analyses were performed using SPSS version 18.0 software (SPSS, Chicago, Ill) was used for data analysis. Descriptive statistics is presented as means ± standard deviation. The data were compared using the t-test for continuous variables. Stuart–Maxwell tests were used to compare paired categorical variables. Local control and overall survival (OS) were calculated using the Kaplan–Meier (K–M) method. Any P < 0.05 indicated a significant difference.
| > Results|| |
Seed implantation characteristics
All patients were treated successfully. The prescription dose was 12,000 cGy, and a postimplantation dose evaluation was routinely conducted to calculate the D90 (i.e., the dose delivered to 90% of the target volume) and V90 (the target volume receiving at least 90% of the prescribed dose). The implanted number of 125 I seeds was 48.17 ± 23.96 for each patient, and the postoperative verification target D90 and V90 values were 11,072 cGy and 94.45% ± 4.08%, respectively. The spinal cord D90 was 4189.32 ± 1740.06 cGy. All 36 lesions were well controlled [Table 2].
Response to treatment
In the median follow-up period of 6 months, 19 patients died from multiple metastasis, and 3 patients remained alive with no evidence of local recurrence or distant metastases. Four cases had subsequent fractures. The response rate was 18/22 (82%), including 10 patients with CR (46%) and 8 patients with PR (36%). In addition, 2/22 patients had SD (9%) and 2/22 had PD (9%). The local control rates at 3, 6, and 12 months were 91.3%, 81.9%, and 81.9%, respectively [Figure 2]a. All patients underwent follow-up MRI. Among the grades of the ESCC, the ESCC grade increased in 4 centrums in 4 people, among whom 2 individuals showed local recurrence, and two others suffered subsequent fractures. The preoperative grade of MESCC ranging from 0 to V was 0, 2.8%, 36.1%, 16.7%, 30.5%, and 13.9%, respectively, while the postoperative MESCC grade ranging from 0 to V changed to 19.5%, 30.5%, 25%, 22.2%, 2.8%, and 0, respectively. Nonparametric tests revealed that the postoperative ESCC score increased significantly [P < 0.05; [Table 3] and [Figure 3]. In addition, 21 of 22 patients suffered various degrees of pain before seed implantation, as reported using the NRS. The mean time to pain relief was 2–3 days after seed implantation. Moreover, the mean NRS scores before and after implantation were 3.45 ± 1.33 and 1.7 ± 1.48, respectively (P < 0.05). Regarding the ASIA grade, class E is most common and accounts for 50% of cases preoperatively, which increased to 68.1% postoperatively. Eleven patients suffered from neurological functional symptoms before operation, and this number was reduced to 8 postoperatively. Two patients suffered neurological deterioration due to subsequent compression fractures. There were no significant differences in changes in the ASIA grade during the 6-month follow-up period. The nerve functional reservation, recovery, and decline rates were 63.7% (14/22), 27.3% (6/22), and 9% (2/22), respectively [Table 4].
|Figure 2: Local control (a) and survival (b) curves for the 22 patients treated with iodine-125 seed implants|
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|Table 3: The metastatic epidural spinal cord compression grade before and after treatment (a median follow-up time of 6 months)|
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|Figure 3: Magnetic resonance imaging revealed changes in the ESCC grade. (a-d) In a patient with HCC T4 metastases, the epidural spinal cord compression grade decreased from preoperative class 5-0. (e-h) In another patient with nonsmall cell lung cancer T6–T7 metastases, the epidural spinal cord compression grade decreased from preoperative class 5-1|
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|Table 4: The American Spinal Injury Association (ASIA) grade before and after treatment (a median follow-up time of 6 months)|
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The median survival time for this 22 patient cohort was 10 months, and the overall 6-, 12-, and 16-month survival rates were 80%, 50.0%, and 21.9%, respectively [K–M curves are shown in [Figure 2]b.
Toxicity and surgical complications
No surgery-related complications, such as fever, infection, or bleeding, were observed. No seeds migrated. Finally, no adverse neurologic sequelae have occurred according to the RTOG criteria.
| > Discussion|| |
In our present study, a new treatment modality was introduced for MESCC patients in addition to decompressive surgical resection (DDSR) and RTx. RTx has been the most common treatment for MESCC since the 1950s. Clinical studies have also established that RTx is a standard treatment for MESCC that results in functional improvement. The optimum dose and treatment plan remain controversial, despite the accepted effectiveness of RTx. Previously, Rades et al. reported a retrospective series of 1304 patients with MESCC. Patients were separated into five RTx schedules of 1 × 8 Gy in 1 day (n = 261), 5 × 4 Gy in 1 week (n = 279), 10 × 3 Gy in 2 weeks (n = 274), 15 × 2.5 Gy in 3 weeks (n = 233), and 20 × 2 Gy in 4 weeks (n = 257). They found that the five RT schedules provided similar functional outcomes, but the protracted schedules yielded lower in-field recurrence rates. Thus, the authors recommended a short-course of RTx of 1 × 8 Gy for patients with poor predicted survival and a long-course RTx of typically 10 × 3 Gy for other patients. In another retrospective study, Rades et al. found that local control, progression-free survival, and OS were significantly higher in MESCC patients who had received ≥ 30 Gy compared with those who had received 30 Gy. Notably, there is a limit because when the radiation dose increases beyond 40 Gy, radiation-related complications also increase. By contrast, brachytherapy has the potential to deliver higher radiation doses to a tumor with less exposure to the spinal cord. The postoperative target D90 reached 11,072 cGy, while no acute or late radiation toxicity occurred. As a complement treatment to radiation, DDSR can effectively improve pain relief, neurological, functional, and spine stability with MESCC patients who have at least a 3-month survival prognosis., However, because of the narrow inclusion criteria, surgery appears to be suitable for only 10%–15% of all patients and is associated with complications that include spinal cord or root injury, extensive bleeding, infection, and dura tears., In this present study, CT-guided 125 I seed implantation is a minimally invasive technique compared with DDSR, but vertebral fracture may occur with in cases with a high Spinal Instability Neoplastic Score (SINS). In our present study, four cases had subsequent compression fractures, including two patients who suffered neurological deterioration, and other cases emerged that exhibited an increase of ESCC grade and pain. Thus, aggressive treatment should be elected for spinal instability patients in cases of compression fracture. Percutaneous vertebroplasty is a minimally invasive treatment for spinal instability and is safe for the treatment of MESCC., For subsequent spinal fractures, we recommend bone cement injection to the centrum for cases with an SINS score >9.
The degree of MESCC represents a significant anatomical factor, and Bilsky established that the six-point ESCC grading system based on T2-weighted MRI is valid and reliable for describing the degree of MESCC. A high ESCC grade indicates a poor prognosis. Back pain is the most common symptom of MESCC and manifests as the first symptom in 83%–95% of patients. When the nerve roots are compressed or invaded, typically observed in high-grade ESCC patients, the pain becomes worse. Our study showed that 125 I seeds can effectively alleviate compression and pain because when seeds become implanted, continuous low energy γ-rays are generated to kill tumor cells, leading to reductions in inflammatory mediators and tumor shrinkage – both events that would relieve spinal cord compression. Another significant factor for patients with MESCC is the duration of survival. Rades et al. established a scoring system to estimate the survival of patients with MESCC. They found that the tumor type, interval between tumor diagnosis and MSCC, the presence of other bone or visceral metastases, ambulatory status, and duration of motor deficits were significant predictors of survival; therefore, these criteria were included in the scoring system. Although the median survival time for patients with MESCC was 3–6 months, there was a trend toward a better median survival time (10 months) with 125 I seed implantation in MESCC patients, suggesting that 125 I seed brachytherapy may prolong the survival of MESCC patients.
125 I seeds have been widely used in the past several decades and proved to be an ideal treatment modality in many malignant tumors and spinal tumor metastases.,,,,, As a low-energy nuclide, the dose of 125 I seeds can rapidly fall off with distance. In addition, the treatment has a half value layer of 1.7 cm in tissues, which can prevent any potential injury to surrounding tissues., Furthermore, there was no occurrence of severe complications during the study. Rogers et al. reported that in 13 patients with spinal cord compression who underwent laminectomy and 125 I seed implants, the median composite total dose of External beam radiotherapy (EBRT) combined with brachytherapy was 131 Gy that was delivered to the tumor and 69.9 Gy to the spinal cord, resulting in durable and excellent local control and ambulatory function. No radiation myelitis occurred during the mean 19.8 months of follow-up, although the recommended spinal cord dose limit is 45 Gy. Our study delivered 110 and 42 Gy to the tumor and spinal cord, respectively. The spinal cord compression was significantly relieved, and no mortality or morbidity was attributable to seed implantation during follow-up. The half-life of the 125 I seeds is 59.4 days; so, the clinical indexes of pain and quality of life were assessed in the 3rd month after surgery.
Some limitations must be considered, including the retrospective nature of our data collection, the limited number of patients, and the analysis of patients from a single institution. It will be necessary to establish a control group in future studies to compare the risks and benefits of 125 I seed brachytherapy with conventional approaches. Nonetheless, this present study provides strong evidence that brachytherapy of 125 I seeds will be beneficial to patients with MESCC.
| > Conclusion|| |
We propose, for the first time, a new palliative treatment for patients with MESCC with fewer complications and better outcomes. The results of this retrospective study suggest that MESCC is sensitive to 125 I seeds. The radiation toxicity and surgical complications were well controlled. Thus, this method is a safe and effective palliative treatment for patients with MESCC that may also prolong OS.
The Department of Pathology, Ultrasound and Radiology of the Southwest Hospital and the Cancer Center, Research Institute of Surgery, Da ping Hospital, the army Medical University performed diagnoses of MESCC and played a critical role in generating this manuscript.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3], [Table 4]