Background: Percutaneous vertebroplasty employs bone cement for injecting into the fractured vertebral body (VB) caused by spinal metastases. Radioactive bone cement and also brachytherapy seeds have been utilized to suppress the tumor growth in the VB.
Objective: This study aims to investigate the dose distributions of low-energy brachytherapy seeds, and to compare them to those of radioactive bone cement, by Monte Carlo simulation.
Material and Methods: In this simulation study, nine CT scan images were imported in Geant4. For the simulation of brachytherapy, I-125, Cs-131, or Pd-103 seeds were positioned in the VB, and for the simulation of vertebroplasty, the VB was filled by a radioactive cement loaded by P-32, Ho-166, Y-90, or Sm-153 radioisotopes. The dose-volume histograms of the VB, and the spinal cord (SC) were obtained after segmentation, considering that the reference dose is the minimum dose covered 95% of the VB.
Results: The SC sparing was improved by using beta-emitting cement because of their steep gradient dose distribution. I-125 seeds and Y-90 radioisotope showed better VB coverage for brachytherapy and vertebroplasty techniques, respectively. Pd-103 seeds and P-32 radioisotope showed better SC sparing for brachytherapy and vertebroplasty, respectively. The minimum mean doses that covered 100% of the VB were 62.0%, 56.5%, and 45.0% for I-125, Cs-131, and Pd-103 seeds, and 28.3%, 28.6%, 32.9%, and 17.7%, for P-32, Ho-166, Y-90, and Sm-153 sources, respectively.
Conclusion: I-125 and Cs-131 seeds may be useful for large tumors filling the entire VB, and also for the extended tumors invading multiple vertebrae. Beta-emitting bone cement is recommended for tumors located near the SC.
Payman Rafiepour (Google Scholar)
Sedigheh Sina (Google Scholar)
The most prevalent site for bone metastases is the spine. Spinal metastases, mainly arising from prostate, breast, and lung primary cancers, cause vertebral body (VB) fracture, spinal cord (SC) compression, neurological deficit, paraplegia, and death [ 1 - 3 ]. In addition to surgery, radiotherapy has an essential role in the treatment of spinal metastases. Stereotactic radiosurgery, intensity-modulated radiotherapy, stereotactic body radiotherapy, and brachytherapy have been used for the treatment of spinal lesions with desirable clinical outcomes [ 4 - 8 ]. The allowable dose delivered to the VB is limited in external beam radiotherapy, due to the radiation tolerance of the SC. Brachytherapy has the advantage of sparing nearby tissues especially the SC by implanting tiny radioactive seeds or beta-emitting plaques near the tumor [ 9 ].
In the case of spinal fracture and deformity, percutaneous vertebroplasty is performed in which the bone cement (PMMA or polymethylmethacrylate) is injected into the collapsed VB through a needle to maintain spine stability and relieve the pain [ 10 , 11 ]. The radioactive bone cement loaded by a uniformly distributed beta-emitting radioisotope (as an added component) was presented to suppress the tumor progression in the VB [ 12 , 13 ]. Recently, combining vertebroplasty and brachytherapy was considered as a minimally invasive method to overcome the spine instability and the tumor growth, simultaneously [ 14 ]. Several studies investigated the feasibility and efficacy of combining vertebroplasty and brachytherapy with clinically acceptable results [ 15 - 20 ].
Dosimetric analysis of radioactive bone cement is essential as a pre-clinical investigation. Hirsch et al. performed a Monte Carlo dosimetric study of radioactive bone cement mixed with 32P, 166Ho, 90Y, 125I, 18F, and 99mTc radioisotopes in a cortical bone phantom [ 13 ], using MCNP v.5 code [ 21 ]. Montaño et al. represented a new bone cement material loaded with 153Sm, 166Ho, and 188Re radioisotopes and used MCNP v.5 code for a dosimetric comparison [ 22 ]. Kaneko et al. evaluated a radiation transport modeling method for dose calculation in a vertebra containing radioactive bone cement, using MCNP extended code (MCNPX v. 2.5) and EBT radiochromic film [ 12 ]. The same group also simulated some clinical scenarios such as bone cement leakage with MCNP v.5 [ 23 ]. However, there are insufficient data for the dose distributions of brachytherapy seeds and beta-emitting bone cement in the spinal canal. In this study, a dosimetric analysis of 125I, 103Pd, and 131Cs brachytherapy seeds as well as radioactive bone cement loaded by uniformly distributed 32P, 90Y, 166Ho, and 153Sm radioisotopes, was conducted using Geant4 Monte Carlo toolkit. The corresponding dose distributions in the VB and the SC were obtained and compared with each other.
Material and Methods
Geant4.10.6 Monte Carlo toolkit [ 24 ] with the standard electromagnetic physics model of “G4EmStandardPhysics_option3” was used in this simulation study. The G4EmStandardPhysics_option3 physics model includes photoelectric effect, pair production, Compton scattering, and Rayleigh scattering data for the interactions of photons and bremsstrahlung, ionization, fluorescence emission, multiple scattering, and positron annihilation data for the interactions of electrons and positrons [ 25 ]. For more accuracy, particle-induced X-ray emission and Auger electron from excited atoms were manually implemented in the physics list. The production range cut was set to 0.1 mm for secondary particles, i.e. the secondary particles with a range of 0.1 mm or lower will be killed in the simulation. With 300 million primary particles, all statistical uncertainties were below 1% in the regions of interest (i.e., SC and VB).
Nine computed tomographie (CT) image slices, with 6 mm thickness, of a normal spinal case (obtained from Imam Hossein Hospital, Tehran) were imported in Geant4. One thoracic VB was determined as a tumor location. The whole VB was considered as the gross tumor volume (GTV), which is the palpable region of tumor seen on the image according to the ICRU Report 50 [ 26 ]. In the case of vertebroplasty, a cylindrical volume with a radius of 14 mm, and a height of 6 mm, composed of PMMA (C5O2H8, density=1.19 g/cm3) was simulated in the VB as the bone cement. This cylinder was cut with a smaller cylindrical section with a radius of 7 mm to make an offset region for the spinal canal as shown in Figure 1a. The bone cement surface was approximately 3 mm away from the SC. Four separate simulations were performed with 32P, 90Y, 166Ho, and 153Sm uniformly distributed in the cement.
For the simulation of brachytherapy, the structure of the Amersham model 6711 seed was simulated with a full length of 4.6 mm. It has a cylindrical silver core with a radius of 0.25 mm, and a length of 3 mm, located inside a 0.05 mm thickness titanium shield [ 27 ]. The outer surface of the core was uniformly coated by low-energy 125I, 103Pd, or 131Cs radioisotopes in this simulation. Thirty seeds were placed in the VB in three CT slices with the 8-9 mm inter-seed spaces on each plane as shown in Figure 1b. The distance from the center of the closest seed to the spinal canal was nearly 8 mm. Note that the position of seeds in this simulation is based on a typical treatment planning system that is not optimal for all patients. The actual seeds position should be calculated based on a treatment plan specialized for each patient [ 28 ]. Since brachytherapy seeds are inserted percutaneously through the pedicles, they are tilted inward on either side of the VB [ 29 ]. Therefore, our simulation of seed positions seems desirable since the entire VB is assumed to be the GTV. Related Nuclear data are shown in Table 1. Beta particles, electrons, gamma, and X-rays are shown by β-, e-, γ, and x symbols, respectively.
|Name||Half-life||Radiation: Energy (MeV) (intensity %)|
|32P||14.28 h||*β-: 1.71 (100%)|
|90Y||64.06 h||β-: 2.28 (100%)|
|166Ho||26.8 h||β-: 1.85 (48.8%), 1.77 (49.9%), 0.394 (1%), 0.394 (1%)|
|γ: 1.38 (1%), 0.080 (6.6%)|
|e-: 0.029 (72%)|
|x: 0.056 (9%), 0.049 (8%), 0.007 (8%)|
|153Sm||46.8 h||β-: 0.810 (20%), 0.710 (49%), 0.640 (30%)|
|γ: 0.103 (28%), 0.070 (5%)|
|e-: 0.045 (135%), 0.043 (63%), 0.006 (10%)|
|125I||60.25 d||γ: 0.035 (7%)|
|e-: 0.018 (246%)|
|x: 0.030 (138%)|
|103Pd||16.96 d||γ: 0.498 (0.011%), 0.362 (0.02%), 0.297 (0.011%)|
|e-: 0.043 (258%)|
|x: 0.021 (77%)|
|131Cs||9.69 d||e-: 0.006 (76%)|
|x: 0.032 (74%), 0.004 (7%)|
|*The β- energies refer to the maximum energy in the beta-emission spectrum|
The pixel values of CT images represent CT numbers or Hounsfield Units. In this scale, water is assigned as a value of 0 and other CT numbers are computed by equation 1:
In which μt and μw are tissue and water linear attenuation coefficients, respectively. The materials defined in the simulation are tabulated in Table 2. Data were obtained from the ICRU report 46 [ 31 ]. A linear interpolation was implemented in Geant4 for the conversion of CT numbers to densities.
|Name||Density (g/cm3)||Components: Element (abundance %)|
|Air||1.29 e-3||N (70.0%), O (30.0%)|
|Lung Inhale||0.210||O (74.9%), C (10.5%), H (10.3%), N (3.10%), S (0.30%), K (0.30%), Na (0.20%), P (0.20%), Cl (0.20%)|
|Lung exhale||0.508||O (74.9%), C (10.5%), H (10.3%), N (3.10%), K (0.30%), S (0.30%), Na (0.20%), P (0.20%), Cl (0.20%)|
|Adipose||0.967||C (59.8%), O (27.8%), H (11.4%), N (0.70%), Cl (0.10%), Na (0.10%), S (0.10%)|
|Breast||0.990||C (50.6%), O (35.8%), H (10.9%), N (2.30%), Na (0.10%), P (0.10%), S (0.10%), Cl (0.10%)|
|Soft tissue||1.00||O (76.2%), N (2.60%), C (11.10%), H (10.10%)|
|Muscle||1.061||O (71.0%), C (14.3%), H (10.20%), N (3.40%), S (0.30%), K (0.30%), P (0.20%), Cl (0.20%), Na (0.10%)|
|Liver||1.071||O (71.6%), C (13.9%), H (10.2%), N (3.00%), K (0.40%), P (0.30%), S (0.30%), Na (0.20%), Cl (0.10%)|
|Spinal Disc||1.10||O (74.4%), C (9.90%), H (9.60%), N (2.20%), P (2.20%), S (0.90%), Na (0.50%), Cl (0.30%)|
|Trabecular bone||1.159||C (40.4%), O (36.7%), H (8.50%), N (5.80%), Ca (4.40%), P (3.40%), Cl (0.20%), S (0.20%), Na (0.10%), K (0.10%), Fe (0.10%), Mg (0.01%)|
|Dense Bone||1.575||O (43.4%), C (23.5%), Ca (14.6%), P (7.20%), H (5.60%), N (5.00%), S (0.30%), Na (0.10%), Cl (0.10%), K (0.10%), Mg (0.01%)|
A cubic mesh with the same resolution of the CT images (512×512 pixel2) was defined to calculate the deposited dose in the voxels. The prescribed dose is usually defined as the minimum dose covering 90% [ 7 ] or 95% [ 8 ] of the GTV. In this simulation, the minimum dose delivered to 95% of the VB (D95%) was determined as the referenced dose for each radioisotope’s radiation field. The tumor and the SC were segmented using MATLAB 2015a code and dose-volume histograms (DVHs) were obtained.
The normalized isodose contours in the central CT slice are shown in Figure 2 for low-energy brachytherapy seeds as well as radioactive bone cement. Figures 3 and 4 show the VB and the SC DVHs for brachytherapy and vertebroplasty, respectively.
According to the DVHs shown in Figures 3 and 4, 125I seeds and 90Y-loaded cement show better VB coverage for brachytherapy and vertebroplasty techniques, respectively. On the other hand, 103Pd seeds and 32P-loaded cement have the advantage of more SC sparing for brachytherapy and vertebroplasty techniques, respectively.
The minimum dose covered 95% of the VB (VB D95%), the minimum dose of the VB (VB Dmin), the minimum dose delivered to 90% of the SC (SC D90%), and the maximum dose of the SC (SC Dmax), in terms of pico-gray per particle are tabulated in Table 3. A representative comparison of V150% (the VB volume received at least 150% of the reference dose), and V200% parameters are shown in Figure 5. Note that the V100% is 95% for all radioisotopes due to the definition of the reference dose (D95%) in this simulation. One should be careful about the occurrence of cold spots in dose distribution. As inferred from Table 3, the ratio of D95% to D100% of the VB reaches up to 161%, 221%, 176%, 353%, 349%, 303%, and 565% for 125I, 103Pd, 131Cs, 32P, 166Ho, 90Y, and 153Sm, respectively. From another perspective, the minimum “mean” dose covered 100% of the VB was 62.0%, 45.0%, 56.5%, 28.3%, 28.6%, 32.9% and 17.7% of the reference dose for 125I, 103Pd, 131Cs, 32P, 166Ho, 90Y, and 153Sm, respectively. The term mean is referred to the average of two separate simulations performed for each radioisotope. Therefore, the occurrence of cold spots in the dose distributions of the cement mixed with 153Sm is more probable. However, the presence of cold spots is not significant for 125I and 131Cs seeds, provided that a maximum inter-seed space of 10 mm is maintained on each plane.
|Dosemetric Parameters (pico-Gy/particle)||Brachytherapy seeds||Radioisotope-loaded bone cement|
|VB: Vertebral Body, SC: Spinal Cord|
The main goal was to compare the dose distributions of various radioactive bone cement with those of low-energy brachytherapy seeds. Although the DVHs of 125I and 131Cs seeds are nearly the same, 125I seeds show an improvement of 9.7% in the tumor coverage. The isodose curves shown in Figure 2 demonstrate the high potential of brachytherapy seeds for the treatment of large lesions in the VB, particularly for tumors that invade more than one vertebra. Nevertheless, due to the deep penetration of the photons emitted from the seeds, sparing of the radiosensitive nearby tissues, i.e., SC and nerve roots need more attention. It is not serious for beta-emitting bone cement since the dose rapidly drops off up to 3 mm from the cement surface [ 12 , 22 ]. Therefore, the employment of beta-emitting bone cement is more interesting for situations in which the tumor is near the spinal canal due to its steep dose gradient. However, the SC sparing is not concerned with beta-emitting cement, high-energy beta particles of 90Y should be considered according to the SC DVH in Figure 3. Although 166Ho and 153Sm are not pure beta-emitting radioisotopes with relatively high-energy photons in their decay schemes, their utilization may not be limited, due to the similarity of their isodose curves to those of 32P. The behavior of the 32P isodose curve is similar to those obtained by Kaneko et al. [ 22 ] since the dose decreases by 50% for each ~0.5 mm incremental distance from the cement surface. The brachytherapy technique provides more flexibility in modifying dose distributions by changing the arrangement and the activity of the seeds that are difficult for radioactive bone cement, particularly for large and extended tumors. Note that the tumor is an incompressible volume limiting the volume of bone cement for injection into the VB, and increasing the cement volume results in increasing the risk of cement leakage [ 32 ]. Therefore, tumor ablation techniques should be performed before the cement injection. The seeds cannot be implanted in the cement, therefore we assumed a VB that is completely occupied by the tumor in the case of brachytherapy. Partial tumor volumes in the VB result in different seed arrangements that need more investigation in a separate simulation. Only tumors located in the VB were considered in this simulation, not the epidural tumors, and for epidural lesions, brachytherapy seeds cannot be used due to their vicinity to the spine and its dose tolerance concern.
Using brachytherapy seeds as the more penetrating sources can be used for large tumors filling the whole VB, and also for the extended tumors in multiple vertebrae. When the tumor is located in the posterior part of the VB near the SC, beta-emitting bone cement (preferably 32P) should be employed at least 4 mm from the SC. Otherwise, the aim of SC sparing may be achieved by using 103Pd seeds with more than 5 mm distance from the SC. From a simulation viewpoint, it is recommended that 125I (or 131Cs) seeds be implanted in the tumor with at least 10 mm distance from the SC. However, more clinical studies should be conducted to assess the feasibility of such radioactive sources in various clinical scenarios.
P. Rafiepour wrote the Monte Carlo simulation code. S. Sina wrote and designed the manuscript. P. Azimi proposed the idea of the study, and provided the CT images. R. Faghihi performed the final editing and revision. All the authors read and approved the final version of the manuscript.
This is a pure simulation study that no ethical approval is required.
Conflict of Interest
- Abdu WA, Provencher LM. Primary bone and metastatic tumors of the cervical spine. Spine. 1999; 23(24):2767-77. DOI | PubMed
- Finkelstein J, Zaveri G, Wai E, Vidmar M, Kreder H, Chow E. A population-based study of surgery for spinal metastases: survival rates and complications. J Bone Joint Surg Br. 2003; 85(7):1045-50. DOI | PubMed
- Jansson KÅ, Bauer HC. Survival, complications and outcome in 282 patients operated for neurological deficit due to thoracic or lumbar spinal metastases. Eur Spine J. 2006; 15(2):196-202. Publisher Full Text | DOI | PubMed
- Ryu S, Fang Yin F, Rock J, Zhu J, Chu A, Kagan E, et al. Image-guided and intensity-modulated radiosurgery for patients with spinal metastasis. Cancer. 2003; 97(8):2013-8. DOI | PubMed
- Sahgal A, Bilsky M, Chang EL, Ma L, Yamada Y, Rhines LD, et al. Stereotactic body radiotherapy for spinal metastases: current status, with a focus on its application in the postoperative patient: a review. J Neurosurg Spine. 2011; 14(2):151-66. DOI | PubMed
- Lu J, Huang W, Wang Z, Gong J, Ding X, Chen Z, Xia N, et al. The safety and efficacy of interstitial 125I seed implantation brachytherapy for metastatic epidural spinal cord compression. J Cancer Res Ther. 2018; 14(7):1549-55. DOI | PubMed
- Cao Q, Wang H, Meng N, Jiang Y, Jiang P, Gao Y, Tian S, et al. CT-guidance interstitial 125 Iodine seed brachytherapy as a salvage therapy for recurrent spinal primary tumors. Radiat Oncol. 2014; 9:301. Publisher Full Text | DOI | PubMed
- Folkert MR, Bilsky MH, Gil’ad NC, Voros L, Oh JH, Zaider M, Laufer I, Yamada Y. Local recurrence outcomes using the 32P intraoperative brachytherapy plaque in the management of malignant lesions of the spine involving the dura. Brachytherapy. 2015; 14(2):202-8. DOI | PubMed
- Zuckerman SL, Lim J, Yamada Y, Bilsky MH, Laufer I. Brachytherapy in spinal tumors: a systematic review. World Neurosurg. 2018; 118:e235-44. DOI | PubMed
- Deramond H, Depriester C, Galibert P, Le Gars D. Percutaneous vertebroplasty with polymethylmethacrylate: technique, indications, and results. Radiol Clin North Am. 1998; 36(3):533-46. DOI | PubMed
- Jensen ME, Evans AJ, Mathis JM, Kallmes DF, Cloft HJ, Dion JE. Percutaneous polymethylmethacrylate vertebroplasty in the treatment of osteoporotic vertebral body compression fractures: technical aspects. AJNR Am J Neuroradiol. 1997; 18(10):1897-904. Publisher Full Text | PubMed
- Kaneko TS, Sehgal V, Skinner HB, Al-Ghazi MS, Ramisinghani NS, Keyak JH. Evaluation of a radiation transport modeling method for radioactive bone cement. Phys Med Biol. 2010; 55(9):2451-63. DOI | PubMed
- Hirsch AE, Medich DC, Rosenstein BS, Martel CB, Hirsch JA. Radioisotopes and vertebral augmentation: dosimetric analysis of a novel approach for the treatment of malignant compression fractures. Radiother Oncol. 2008; 87(1):119-26. DOI | PubMed
- Yang Z, Yang D, Xie L, Sun Y, Huang Y, Sun H, Liu P, Wu Z. Treatment of metastatic spinal tumors by percutaneous vertebroplasty versus percutaneous vertebroplasty combined with interstitial implantation of 125I seeds. Acta Radiol. 2009; 50(10):1142-8. DOI | PubMed
- Cardoso ER, Ashamalla H, Weng L, Mokhtar B, Ali S, Macedon M, Guirguis A. Percutaneous tumor curettage and interstitial delivery of samarium-153 coupled with kyphoplasty for treatment of vertebral metastases. J Neurosurg Spine. 2009; 10(4):336-42. DOI | PubMed
- Lu J, Deng J, Zhao H, Shi M, Wang J, Zhao L. Safety and feasibility of percutaneous vertebroplasty with radioactive 153Sm PMMA in an animal model. Eur J Radiol. 2011; 78(2):296-301. DOI | PubMed
- Lu CW, Shao J, Wu YG, Wang C, Wu JH, Lv RX, et al. Which Combination Treatment Is Better for Spinal Metastasis: Percutaneous Vertebroplasty With Radiofrequency Ablation, 125I Seed, Zoledronic Acid, or Radiotherapy?. Am J Ther. 2019; 26(1):e38-44. DOI | PubMed
- Yang Z, Tan J, Zhao R, Wang J, Sun H, Wang X, Xu L, Jiang H, Zhang J. Clinical investigations on the spinal osteoblastic metastasis treated by combination of percutaneous vertebroplasty and 125I seeds implantation versus radiotherapy. Cancer Biother Radiopharm. 2013; 28(1):58-64. Publisher Full Text | DOI | PubMed
- Li T, Li J, Wang Z, Liu B, Han D, Wang P. A preliminary comparative clinical study of vertebroplasty with multineedle or single-needle interstitial implantation of 125I seeds in the treatment of osteolytic metastatic vertebral tumors. J Neurosurg Spine. 2014; 20(4):430-5. DOI | PubMed
- Yang Z, Zhang Y, Xu D, Maccauro G, Rossi B, Jiang H, Wang J, et al. Percutaneous vertebroplasty combined with interstitial implantation of 125 I seeds in banna mini-pigs. World J Surg Oncol. 2013; 11:46. Publisher Full Text | DOI | PubMed
- Goorley T, James M, Booth T, Brown F, Bull J, et al. Initial MCNP6 release overview. Nucl Technol. 2012; 180(3):298-315. DOI
- Montaño CJ, Campos TP. Radioactive cement of PMMA and HAP-Sm-153, Ho-166, or RE-188 for bone metastasis treatment. Acta Ortop Bras. 2019; 27(1):64-8. Publisher Full Text | DOI | PubMed
- Kaneko TS, Sehgal V, Skinner HB, Al-Ghazi MS, Ramsinghani NS, Miranda MM, Keyak JH. Radioactive bone cement for the treatment of spinal metastases: a dosimetric analysis of simulated clinical scenarios. Phys Med Biol. 2012; 57(13):4387-401. DOI | PubMed
- Collaboration GE, Agostinelli S. GEANT4–a simulation toolkit. Nucl Instrum Meth A. 2003; 506(25):250-303. DOI
- Geant4 Collaboration. Guide For Physics Lists. Year. Available from: https://geant4userdoc.web.cern.ch/UsersGuides/PhysicsListGuide/fo/PhysicsListGuide.pdf.
- International Commission on Radiation Units and Measurements. Prescribing, recording and reporting photon beam therapy. ICRUM; 1993.
- Rivard MJ, Coursey BM, DeWerd LA, Hanson WF, et al. Update of AAPM Task Group No. 43 Report: A revised AAPM protocol for brachytherapy dose calculations. Med Phys. 2004; 31(3):633-74. DOI | PubMed
- Wang J, Chai S, Zheng G, Jiang Y, Ji Z, Guo F, Zhuang H, Zhang K. Expert consensus statement on computed tomography-guided 125I radioactive seeds permanent interstitial brachytherapy. J Cancer Res Ther. 2018; 14(1):12-17. DOI | PubMed
- 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 Cancer Res Ther. 2019; 15(4):807-12. DOI | PubMed
- National Nuclear Data Center. Brookhaven National Laboratory. USA; 2012.
- ICRU. ICRU: United States; 1992.
- Cotten A, Dewatre F, Cortet B, Assaker R, Leblond D, et al. Percutaneous vertebroplasty for osteolytic metastases and myeloma: effects of the percentage of lesion filling and the leakage of methyl methacrylate at clinical follow-up. Radiology. 1996; 200(2):525-30. DOI | PubMed