|Year : 2018 | Volume
| Issue : 7 | Page : 1549-1555
The safety and efficacy of interstitial 125I seed implantation brachytherapy for metastatic epidural spinal cord compression
Jian Lu1, Wei Huang2, Zhongmin Wang3, Ju Gong1, Xiaoyi Ding2, Zhijin Chen1, Ning Xia1, Nannan Yang1, Zhiyuan Wu2, Chen Wang4, Jun Chen4
1 Department of Radiology, Ruijin Hospital Luwan Branch, Shanghai 200020, China
2 Department of Interventional Radiology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200020, China
3 Department of Interventional Radiology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200020; Department of Interventional Radiology, The Third Affiliated Hospital of the Medical College of Shihezi University, Xinjiang, 832008, China
4 Department of Interventional Radiology, The Third Affiliated Hospital of the Medical College of Shihezi University, Xinjiang, 832008, China
|Date of Web Publication||19-Dec-2018|
Department of Interventional Radiology, The Third Affiliated Hospital of the Medical College of Shihezi University, Xinjiang 832008; Department of Interventional Radiology, School of Medicine, Ruijin Hospital, Shanghai Jiao Tong University, Shanghai 200020
Source of Support: None, Conflict of Interest: None
Objective: The objective of this study is to investigate the safety and efficacy of 125I seed interstitial implantation brachytherapy for metastatic epidural spinal cord compression (MESCC) as well as the life quality of patients.
Materials and Methods: From April 2009 to May 2015, 28 patients who met the eligibility criteria were retrospectively reviewed. The number of implanted 125I seeds ranged from 7 to 62, with appropriate activity of 0.5–0.8 mCi. The postplan showed that the matched peripheral dose (MPD) of tumors was 80–140 Gy. The duration of follow-up ranged from 1 to 32 months with a median of 18 months. Visual analog scale (VAS), Karnofsky Performance Scale (KPS), and motor performance were evaluated before and after treatment.
Results: Seed implantation was well tolerated by all patients. Pain was obviously alleviated in all patients. VAS score of patients was significantly decreased from 4.89 ± 1.52 before treatment to 1.61 ± 1.20 after treatment, and KPS score was significantly increased from 73.93 ± 12.27 to 86.76 ± 10.90 (P < 0.05). The local control rates of 1, 2, and 3 years were 77%, 34%, and 14%, respectively, with a median of 19 months (7–32 months). The survival rates of 1, 2, and 3 years were 81%, 54%, and 14%, respectively, with a median of 25 months. Seven (100%) nonwalking patients regained motor ability. No myelopathy or other neurologic sequelae were encountered.
Conclusion: Interstitial 125I seed implantation brachytherapy may be a promising local therapy, which was an alternative and palliative way for treating MESCC.
Keywords: Brachytherapy, computed tomography guided, iodine-125 seed, metastatic epidural spinal cord compression
|How to cite this article:|
Lu J, Huang W, Wang Z, Gong J, Ding X, Chen Z, Xia N, Yang N, Wu Z, Wang C, Chen J. The safety and efficacy of interstitial 125I seed implantation brachytherapy for metastatic epidural spinal cord compression. J Can Res Ther 2018;14:1549-55
|How to cite this URL:|
Lu J, Huang W, Wang Z, Gong J, Ding X, Chen Z, Xia N, Yang N, Wu Z, Wang C, Chen J. The safety and efficacy of interstitial 125I seed implantation brachytherapy for metastatic epidural spinal cord compression. J Can Res Ther [serial online] 2018 [cited 2020 Jan 19];14:1549-55. Available from: http://www.cancerjournal.net/text.asp?2018/14/7/1549/247734
| > Introduction|| |
Primary malignant tumors of the spine have been rare. However, the spine is the largest repository of cancellous bone in the body, with abundant blood supply. Therefore, the spine has been highly susceptible to metastatic deposits from systemic malignancy., Metastatic epidural spinal cord compression (MESCC) has been one of common complications of cancers, resulted from tumor-related compression of the thecal sac and spinal cord., It has been clinically observed in approximately 3%–10% of cancer-related deaths. For patients, MESCC leads to a pronounced deterioration toward quality of life, and it was oncologic emergency condition pending rapid onset of therapy. The potential of developing long-term and severe complications is in urgent need of an immediate and effective palliative therapy. The most appropriate treatment for MESCC has been controversial. With the development of interventional therapy, radioactive iodine-125 (125I) seed implantation has been widely applied in treating many primary and secondary malignant tumors, achieving satisfactory clinical outcomes.,,, Because the long half-life and low energy of 125I seed implantation, tumor cells could be persistently destroyed while surrounding normal tissues could be also relatively safe.,
| > Materials and Methods|| |
The definition of epidural MESCC has been changed during last few decades. The most recent version included both clinical and radiographic criteria and encompassed the anatomy of the cord and the cauda equina. The minimum radiologic evidence for cord compression was indentation of the theca at the level of clinical features. Clinical features include any or all of the following items: pain (local or radicular), weakness, sensory disturbance, and/or evidence of sphincter dysfunction. This definition had been adopted in our institution, and patients with local or radicular pain were MESCC even in the absence of neurologic symptoms, providing that cord compression was revealed at magnetic resonance imaging (MRI) and/or computed tomography (CT).
For early diagnosis, MRI or CT was prescribed for all cancer patients with back pain, osteolysis, and/or positive bone scan, even in the absence of neurologic symptoms from spinal cord compression. All included patients fulfilled following inclusion criteria: MESCC was diagnosed by MRI or CT in patients with progressive malignant tumors; the expected survival time was >3 months; Karnofsky Performance Scale (KPS) was >60; the patients were not suitable for surgery or unwilling to take conventional radiation therapy (CRT) for various reasons; and informed consents were obtained.
Characteristics of patient
Between April 2009 and May 2015, 28 patients received 125I seed interstitial implantation for the treatment of MESCC in our institution. Patients' baseline characteristics were presented [Table 1]. All the primary tumors were confirmed by operation or puncture biopsy. Extraspinal bone metastasis was not presented in all cases. Ten (35.71%) and 3 (10.71%) patients had one or multiple systemic metastases, respectively (bone excluded), at the time of presentation. Eighteen (64.29%) patients reported pain (either nociceptive or neurologic pain) at the time of MESCC diagnosis, of which 10 (35.71%) patients presented with hyperalgesia.
The study was approved by the institutional review board, and written informed consent was obtained from all patients before study enrollment.
Preparation of seed implantation
For examination of the spine, especially for suspected MESCC, MRI was the most sensitive imaging procedure. The imaging technique consisted of MRI with whole-spine sagittal T1-weighted imaging (T1WI) and T2WI imaging and axial T1WI imaging. Additional MRI techniques were applied if clinically appropriate. There was a central review of all MRI scan for the confirmation of MESCC.
Before treatment, CT scan was also examined according to the location of the lesions revealed on MRI images. A Siemens CT scanner with following spinal imaging conditions was applied: 120 kV, 275 mA, and a 5 mm width. The 125I-sealed seed sources were supplied by XinKe Pharmaceutical Ltd., (XinKe Pharmaceutical Ltd., Shanghai, China). Before the 125I seed implantation brachytherapy, the Fudan TPS2.00 brachytherapy planning system (Fudan University, Shanghai, China) was applied to determine the number and position of the 125I seed pending implantation. It aimed to generate isodose curves of different percentages of predicted tumor regression and a dose-volume histogram. The prescribed minimal peripheral dose (MPD) of 90–130 Gy was designed to encompass the planned target volume (PTV)., PTV was a 0.5–1.5 cm expansion of the gross tumor volume. PTV was covered by 90% of the isodose curves. The dose distribution for organ at risk (OAR) was also calculated with TPS.
For the 125I seed implantation, 18-G implantation needles and a turntable implantation gun (XinKe Pharmaceutical Ltd., Shanghai, China) were applied. The 125I seeds were manufactured from silver rods, which absorbed 125I, and were enclosed in a titanium capsule welded by a laser. The diameter and length of each seed were 0.8 and 4.5 mm, respectively. The wall thickness of the titanium capsule was 0.05 mm. The characteristic parameters of 125I was as follows: producing gamma-rays (5%, 35 keV and 95%, 28 keV) with a half-life of 59.6 days, a half-value thickness of 0.025 mm of lead, a penetration of 17 mm, an incipient rate of 7 cGy/h, and activity of 0.5–0.8 mCi.
Computed tomography-guided implantation protocol
The patients were placed in the prone position. CT imaging was performed at 5-mm intervals. Seed placement was individualized according to the certain patient and tumor anatomy. The puncture region was sterilized and locally anesthetized with 1% lidocaine. The position of puncture point was determined based on the title angle of the pedicle, the distance between the puncture point and the spinous process, and the depth from the skin to the pedicle, all of which had been determined by CT imaging. Then, 18-G implantation needles were inserted, with approximately a 1-cm distance between adjacent needles. The direction of the needle tip was adjusted constantly during the implantation to achieve an ideal distribution of the 125I seeds. During the needle placement, care was taken to keep the needles at least 1 cm away from large blood vessels. Immediate nerve root contact was averted. All the 125I seeds were placed with distance of 0.5–1.0 cm from one another. Then, the site of implantation puncture was bandaged and compressed to achieve hemostasis.
The KPS was applied to evaluate functional status and to predict cancer treatment outcome, survival, and quality of life. The criteria of KPS scoring were from 0 to 100, indicating death to no evidence of disease. The visual analog scale (VAS) was involved to determine pain intensity. The score from 0 to 10 was evaluated with a VAS ruler, indicating no pain to extreme pain. Based on physical examination, motor performance was graded according to Tomita's groups: Group I, ability to walk without support; Group II, ability to walk with support; Group III, inability to walk; and Group IV, paraplegic. The adopted response criteria were as follows: patients who were able to walk before and after treatment and those unable to walk before treatment but recovered walking ability after treatment were consider as responders.
In addition to KPS, VAS, and motor performance, local control of MESCC and survival were also evaluated. Local control was defined as the absence of neurological progression in the seed-implanted spine. Recurrence was defined as follows: either as a recurrence of motor deficits if therapy had led to improved motor performance or as a progression of motor deficits if therapy had resulted in no changed motor deficits. The clinical diagnosis of local failure of MESCC was confirmed with MRI. Local control and survival were calculated since the 1st day of seed implantation.
Follow-up and statistical analysis
The follow-up data were collected 1 month, 3 months, and then every 3 months for the 1st year and every 6 months thereafter. The data included postintervention clinical examinations, blood sampling, CT, and/or MRI examinations of the spine. Follow-up CT scans for evaluating response were obtained for all the patients at various intervals after implantation. To calculate survival, all deaths were scored as an event. The time of local control and survival were calculated from the date of seed implantation to the date of death or the last follow-up. The local control rates and survival rates were calculated by the Kaplan–Meier method, with SPSS 18.0 software (IBM, Armonk, NY, USA).
| > Results|| |
Response to treatment
Twenty-eight cases (100%) were followed and no patient was lost to follow-up, with a median follow-up time of 18 months (ranged 1–32 months). The success rate of the puncture operations was 100%. The average number of implanted seeds per patient was 31 (ranged 7–62). The activity of the seeds ranged from 0.5 to 0.8 mCi, and MPD was 90–130 Gy. The PTV edge was covered by 80%–90% of the isodose curves [Figure 1]. The main OARs were shown [Table 2]. Other OARs all met with the tolerance constraints.
|Figure 1: A 42-year-old male with metastatic pancreatic cancer. Sagittal T2-weighted magnetic resonance imaging before (a) and after (b) treatment with spinal cord compression at L4 vertebra. Computed tomography scan before (c) and after (d) 125I seed implantation. (e-f) Computed tomography-guided multipuncture needle parallel implantation. (g) The dose-volume histograms of gross tumor volume after seed implantation|
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Local control and survival
For the reason of poor health, many patients refused to take further therapy after seed implantation, and only 6 patients received chemotherapy of 2–6 cycles. After follow-up, the local control rates of 1, 2, and 3 years were 77%, 34%, and 14%, respectively, with a median of 19 months (7–32 months) [Figure 2]. Eight (28.57%) patients failed in local control. One of these eight patients showed tumor recurrence at 10 months after seed implantation and died of dissemination at 14 months after implantation. One of these eight patients showed tumor recurrence at 25 months after seed implantation and refused further therapy. This patient died of acute myocardial infarction 3 months after recurrence. One of eight patients showed tumor recurrence at 23 months after seed implantation and refused further therapy. This patient survived 26 months after implantation. Other five of these eight patients presented tumor recurrence at 10, 17, 20, and 22 months, who received a second round of seed implantation. One of these five patients survived 13 months after seed implantation. Four of five patients manifested metastases and died 3–8 months after the second seed implantation.
The survival rates of 1, 2, and 3 years were 81%, 54%, and 14%, respectively, with a median of 25 months [Figure 3]. Eleven (39.29%) patients were still alive, of which nine patients showed no evidence of local recurrence or distant metastases. One of these eleven patients showed recurrence and received a second round of seed implantation. One of eleven patients showed recurrence and refused to take further therapy. Fifteen patients (53.57%) developed distant metastases and died. One (3.57%) patient died of acute cerebral hemorrhage without local recurrence or distant metastases. One (3.57%) patient died of acute myocardial infarction with local recurrence.
All patients suffered varying degrees of pain before 125I seed implantation, with VAS ranged from 2 to 8. The mean time of pain relief was 2–3 days after the procedure. Mean VAS scores were decreased from 4.89 ± 1.52 to 1.61 ± 1.20 after implantation. The efficacy rate was 100% (P < 0.05).
Karnofsky performance scale score
The KPS scores before and after implantation were 73.93 ± 12.27 and 86.76 ± 10.90, respectively, suggesting that scores of performance status after treatment were significantly increased compared to those of before treatment. The difference was statistically significant (P < 0.05).
The response rates were evaluated based on Tomita's functional motor grading system. All (100%) patients with walking ability maintained this function. Motor ability was regained in 7 (100%) patients unable to walk (Group III) [Table 3].
No mortality or morbidity was attributable to the 125I seed implantation. No serious complication, such as fever, infection, or osteoradionecrosis, was observed during the follow-up. No 125I seed was lost or migrated to other tissue or organ. Five patients developed a hemorrhage at the puncture site, which was stopped by local compression in all five cases. Two patients developed pitting edema of both legs 15 months after treatment.
| > Discussion|| |
The epidural space of the spinal cord would be primarily invaded by metastatic tumors. The intramedullary, intradural, and leptomeningeal diseases have been rarely seen. In the early stages of neurologic deficits, there would be stenosis and obstruction of the epidural venous plexus and blood flow compromise in the arterial and venous circulation, leading to venous hypertension and white matter edema. These conditions would eventually develop to be ischemia due to complete obstruction of blood flow within the arterioles in the deep white matter of the spinal cord. Once infarction occurs, the damage is permanent. The goal for the MESCC treatment is to achieve one or more of the following items: preservation neurological functions (especially the maintenance of ambulation), preservation or restoration of spinal stability, control of intractable pain, tumor debulking/cytoreduction to improve the efficacy of radiotherapy, and prolongation of survival in a few cases.
The application of corticosteroids in the treatment of MESCC has been widespread and dated back several decades. This treatment has been generally considered as an adjuvant to other treatment modalities, particularly conventional radiotherapy (CRT). Several studies have supported the application of corticosteroids in MESCC;, however, it should be noted the high incidence of serious side effects, especially in patients receiving high doses.
Modern surgical approaches have been successful for the treatment of MESCC. Neurologic improvement, ambulatory function recovery, and pain relief could be noted in patients after surgery. However, the patient selection has been imperative for surgery, and not all MESCC patients are eligible for surgery. Surgery would not be available for multiple spinal metastases. Life expectancy and the tolerance of patients would be important factors. The tolerance toward operation was related to the age of patients, and more complications would be observed in patients older than 65 years, compared to those younger than 65 years. Furthermore, spinal surgery would bring about certain risks. In a randomized trial of 101 patients, 12% and 40% of serious surgery-related complications were associated with primary surgery and salvage surgery, respectively.
Spine stereotactic body radiation therapy has been an emerging therapy for patients with spinal metastases. The most prominent serious late toxicity has been reported as vertebral compression fracture (VCF)., Fracture progression was firstly reported in 39% of 71 sites treated in the Memorial Sloan-Kettering Cancer Center series and in 20% of 123 vertebral sites treated in the MD Anderson Cancer Center series. The high rates of VCF have been alarmed because the patients may suffer the risk of further surgical interventions for salvaging the treatment-induced VCF.
The implantation of radioactive isotopes for the treatment of many carcinomas has been applied for past several decades. Numerous studies have confirmed that the implantation of radioactive 125I seeds was a safe and effective method for treating malignant tumors.,, There are several advantages in 125I seed-based radiotherapy: (1) Radiation from 125I seeds was characterized by attenuating over a short distance, which could maintain a high accumulative dose (up to 160 Gy) within the tumor and minimize the irradiation to surrounding normal tissues. (2) Tumor cells could be continuously destroyed by 125I seeds, through keeping cell cycle arrest and promoting tumor stem cell apoptosis. (3) The radiation distance was only about 1.7 cm, which eliminated potential damage to the physician, staff, and families. (4) The internal irradiation could be lasted for relatively long time, which could be up to 180 days. (5) The distribution of 125I seeds could be arranged selectively according to the tumor anatomy.,,,,,
The therapeutic effects of 125I interstitial brachytherapy on transplantation tumor of human pancreatic carcinoma have been evaluated in BALB/c-nu mice. After 125I interstitial brachytherapy, ionizing radiation made sufficient biological effects on proliferating phase tumor cells, leading to tissues damage. Thus, the lesion tissue could be effectively restrained or destroyed. Cells under continuous irradiation would present with prolificacy loss, metabolic disorders, and apoptosis.
The biological effects were compared between 125I seeds based continuous radiation and 60 Co γ-ray radiation on non-small cell lung cancer (NSCLC) cells. The experiment revealed that, after irradiation with 125I seeds, there was lower survival fraction, more pronounced cell cycle arrest, and higher apoptotic ratio for NSCLC cells than that of after 60 Co γ-ray radiation. However, little change was observed in the apoptotic ratio and expression of apoptosis-related proteins in normal BEAS-2B cells receiving the same treatment.
The implantation and distribution of radioactive seeds should be optimized based on the volume and density of the tumor as well as its relationship with adjacent vital organs. The precise implantation and reasonable distribution of seeds could achieve directional blasting, maximum destruction to tumor cells, and minimal damage to normal tissue. The 125I seeds could be arranged selectively according to the asymmetrical growth of the tumor. Our study revealed key steps of this procedure that required attentions. In the deployment plan, the source energy, target size, nearby OARs, and insertion procedures were all taken into account. During needle placement, the operator should take care to keep the needles at least 1 cm away from large blood vessels and the spine. The 125I seeds were implanted at interval of 1.0 cm. The internal irradiation lasted for relatively long time, which could be up to 180 days.
The implantation of radioactive isotopes for the treatment of MESCC can make effects on alleviating pain, preserving or improving neurologic function, achieving mechanical stability, promoting local tumor control, and improving quality of life. This is a potential alternative therapy of MESCC for achieving pain relief. Our study had certain limitations, including limited study period and small sample size. However, our results were statistically significant. Further studies with larger sample size should be performed for obtaining more accurate results.
| > Conclusion|| |
The aims of our study were to evaluate the safety and outcomes of 125I seed interstitial implantation for MESCC as well as the life quality of patients.
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]