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ORIGINAL ARTICLE
Year : 2020  |  Volume : 16  |  Issue : 6  |  Page : 1470-1475

Comparing two radiotherapy techniques of whole central nervous system tumors, considering tumor and critical organs' dose provided by treatment planning system and direct measurement


1 Medical Physics Research Center, Mashhad University of Medical Sciences, Mashhad, Iran
2 Cancer Research Center, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran

Date of Submission25-Dec-2016
Date of Decision30-Sep-2017
Date of Acceptance25-Feb-2018
Date of Web Publication24-Oct-2018

Correspondence Address:
Shokouhozaman Soleymanifard
Mashhad University of Medical Sciences, Pardis-e-Daneshgah, Vakil Abad Boulevard, Mashhad
Iran
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_1425_16

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 > Abstract 


Aims: In central nervous system (CNS) tumors, surgery combined with radiotherapy may cure many tumors. The basic technique in conventional radiotherapy is craniospinal radiotherapy; in this technique, spinal cord can be treated with electron or photon beams. This study was aimed to compare two radiotherapy techniques in craniospinal radiotherapy, (a) treatment of spine with a single photon beam and (b) with a combination of photon and electron beams.
Materials and Methods: The two techniques were planned. In the first technique, both brain and spine were irradiated with 6 MV photon beams. In the second technique, brain was irradiated with 6 MV photon and spine with 18 MeV electron beams. To compensate the dose deficiency in lumbar area, an anterior field of 15 MV photon beam was also applied in the second technique. The dose to target volume and organ at risks (OARs) were measured by thermoluminescent dosimeter and compared with the corresponding values calculated by Isogray treatment planning system.
Results: OARs including heart, mandible, thyroid, and lungs received lower dose from technique 2 compared with technique 1; kidneys were exceptions which received higher dose in the technique 2.
Conclusions: The dose to thyroid, mandible, heart, and lungs were lower in technique 2, while kidneys received higher dose in technique 2. This was caused by using the anterior 15 MV photon beam. Based on these results, for children, instead of photon beam for treatment of spinal cord, it is wiser to use electron beam.

Keywords: Central nervous system, craniospinal radiotherapy, critical organs, thermoluminescent dosimeter


How to cite this article:
Momeni S, Bahreyni Toosi MT, Anvari K, Gholamhosseinian H, Soleymanifard S. Comparing two radiotherapy techniques of whole central nervous system tumors, considering tumor and critical organs' dose provided by treatment planning system and direct measurement. J Can Res Ther 2020;16:1470-5

How to cite this URL:
Momeni S, Bahreyni Toosi MT, Anvari K, Gholamhosseinian H, Soleymanifard S. Comparing two radiotherapy techniques of whole central nervous system tumors, considering tumor and critical organs' dose provided by treatment planning system and direct measurement. J Can Res Ther [serial online] 2020 [cited 2021 Oct 28];16:1470-5. Available from: https://www.cancerjournal.net/text.asp?2020/16/6/1470/243484




 > Introduction Top


In central nervous system (CNS) malignancy, surgery combined with radiotherapy may cure the tumors.[1] Therefore, adjuvant therapies such as radiotherapy are required. The basic technique used in conventional radiotherapy is craniospinal radiotherapy that includes opposed lateral fields irradiating the brain and one or more posterior spinal fields to cover the entire spinal cord. Craniospinal radiotherapy is a complex technique because of the need to match the lateral fields to treat the brain with a posterior field which treats the spinal axis.[2] Since the target volumes are overlapping with several critical organs, side effects following radiotherapy may be severe. These may include hearing loss, cardiac disease, hypothyroidism, neurocognitive deficits, and reduction in the patient's learning and mental skills at the learning age;[3],[4],[5],[6],[7] in addition, there is a risk of inducing secondary cancers.[8]

When radiotherapy and chemotherapy are combined, the total dose to the craniospinal axis is reduced successfully from 35–36 Gy to 23.4 Gy, while maintaining a dose of 54 Gy to the posterior cranial fossa, and this treatment protocol results in a lower risk of long-term side effects.[9] One way to reduce the late side effects associated with radiotherapy is reduction of the absorbed dose to the craniospinal axis. Thus, improving radiotherapy technique is essential. Another approach to reduce the risk of side effects is to decrease the dose to the organs outside the target volume while maintaining sufficient dose to the target volume. Some techniques could potentially be used for approaching this aim, i.e., electron therapy, intensity-modulated radiation therapy (IMRT), and intensity-modulated proton therapy (IMPT).

Most radiotherapy centers in Iran utilize photon beams rather than electron beams for the treatment of spinal component of craniospinal radiation.

However, the potential advantage of electron therapy in craniospinal radiotherapy is the steeper dose gradient and thus lower dose to anterior structures, which may result in less acute and late toxicity.

To determine whether electron beams are likely to have clinical advantages, we have compared absorbed dose to critical normal tissues from photon and electron beams which are potent to be irradiated as a result of craniospinal irradiation (CSI).


 > Materials and Methods Top


Calibration of thermoluminescent dosimeter-100 and thermoluminescent dosimeter-700

TLD, type TLD-100 (Harshaw-Bicron, Cleveland, OH, USA) 3 mm × 3 mm × 0.9 mm was used to measure the dose delivered to Rando phantom following irradiation with photon and TLD-700 (ProRad-Germany) of similar dimensions to TLD-100 was used to measure electron beams.

Sixty-nine TLD-100 chips put at predetermined points of preselected slices of the phantom. TLDs were individually calibrated. Calibration was performed in 3 stages. First 10 TLD chips were irradiated with 6 MV X-rays to determine their efficiency correction coefficients (ECC). In Stage 2, the same chips were irradiated by a specified dose (0.5 Gy) to determine the reader correction factor. In Stage 3, chips were irradiated with 0.5 Gy, and their individual ECCs were determined. The same procedures were performed for TLD-700, except the total number of TLDs which were calibrated (55 instead of 69) and the radiation type used to irradiate the TLDs (18 MeV electrons instead of 6 MV X-rays).

Simulation and treatment planning

Rando phantom (the Phantom Laboratory, NY, USA) was used as a hypothetical patient. Cross-sectional images of the phantom were provided using a computed tomography (CT) scan machine (Neusoft model). During simulation, the phantom was placed in prone position with neck extended so that the divergence of spinal field could exit below the mandible (the phantom was modified to be extended in the neck area).

CT spacing was 3 mm for brain and 5 mm for the spine. The phantom was marked with sagittal and lateral laser lines during the simulation. Then, CT scans were transferred to Precise Elekta treatment planning system (TPS). All tissues of Rando Phantom except bones, lungs, and air cavities (sinuses) are made of a homogeneous material, such that soft tissues can only be distinguished based on skeletal landmarks. Therefore, considering these landmarks, contouring was implemented by an experienced oncologist, and based on his expertise. Posterior cranial fossa (planning target volume [PTV]), brain, and spinal canal (clinical target volume [CTV]) were contoured as the target volumes. Organs at risk including chiasma, thyroid, mandible, heart, right and left lung, right and left kidney were contoured as well. Then, two treatment techniques were planned to treat the target volume [Figure 1].
Figure 1: Adjustment of the radiation fields in technique 1 (a) and 2 (b)

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  1. In technique 1, at first, the cranium was irradiated with two lateral opposed fields. The cranial fields covered the whole brain and extended caudally up to 1 cm above the shoulder, then localized field irradiated to posterior fossa. To avoid overlap between cranial and upper spine fields and eliminate divergence of the cranial fields into the spinal field, the couch was turned 6° (clockwise) for the left lateral cranial field and 4° (anticlockwise) for the right lateral cranial field. For cranial field, collimators were rotated 9° (clockwise).


  2. For irradiation the spinal cord two posterior long thin spinal fields were used to cover the whole spine. The superior border of the upper spinal field touched the inferior border of the cranial field, and the inferior border of the upper spinal field touched the superior border of the lower spinal field. The full multileaf collimators' length was opened to treat the spine. The upper spine field was considered from the first cervical vertebrae down to the first lumbar vertebrae and the lower spine field from the second lumbar vertebra down to the second sacral vertebrae.

  3. In technique 2, brain was treated the same as technique 1. However, spine was irradiated with three 18 MeV electrons fields (cervical, dorsal, and lumbar spinal fields). Since spinal cord in lumbar area is located in a deeper depth compared to other areas, electron beam did not provide sufficient dose for this area. Therefore, a 15 MV photon field was applied anteriorly to compensate the dose deficiency. Dose received by target volume and organs at risks was calculated by TPS.


Treatment

Linear accelerator precise model, made in Elekta Company, was used for craniospinal radiotherapy. This accelerator is able to produce X-rays with energies equal to 6, 10, and 15 MV and electron beams with energies equal to 6, 8, 10, 15, and 18 MeV.

For each technique and each measurement, TLDs were placed in small holes improvised in the phantom slices that corresponded to the location of the organs of interest.

For technique 1, plan was performed based on TPS. 6 MV photon beams were used for irradiation of cranial and spinal fields. Irradiation was performed for 3 times to increase the measurement accuracy, and the results were averaged. Adjustment of the radiation fields in the first technique is shown in [Figure 1]a.

For technique 2, lateral cranial fields were irradiated with 6 MV photon beams, and spinal fields were irradiated with 18 MeV electron beams. For the lumbar area, in addition to a posterior electron field, an anterior 15 MV photon field was used as well. Adjustment of the radiation fields in the second technique is shown in [Figure 1]b.

The PTV and CTV prescribed dose for the two techniques was 54 and 36 Gy, respectively, in 20 fractions, with a daily fraction of 1.8 Gy. Whenever irradiation was performed with photon, TLD-100 chips were used to measure the dose, and whenever electron beam was used, TLD-700 chips were used. The doses of the points which were irradiated with both radiations were obtained based on the sum of the two measurements.

The number of dosimeters placed in every organ and technique separately has shown in [Table 1].
Table 1: The number of thermoluminescent dosimeters in two techniques

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Through TPS calculation, point doses of the points filled with TLDs and dose-volume histograms (DVH) of countered organs were obtained and compared for the two techniques.

Statistical analyses

The results were analyzed using SPSS software. Statistical analyses were performed using Kolmogorov–Smirnov tests to determine data distribution. Paired sample t-test was employed to compare the data obtained for two techniques.


 > Results Top


The results of the practical dosimetry

The data presented in [Table 2] are from practical dosimetry. These data illustrate the absorbed doses in the tumor and critical organs from TLD measurement as a result of the complete treatment course (36 Gy for CTV and 54 Gy for PTV); the recorded doses are the means of point doses in each organ which were multiplied by 20 (20 sessions of 1.8 Gy daily fractions).
Table 2: Average absorbed dose and P value between technique 1 and 2 in the interest organs and tumor volume resulted from practical dosimetry

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All data were distributed normally (P > 0.05), and statistical analysis from paired-samples t-test showed that the doses to the mandible, heart, thyroid, lungs, and kidneys are significantly different in the two techniques (P < 0.05).

The results of treatment planning system

The results of the TPS are displayed in two ways:

  1. The mean dose ± standard deviation delivered to the tumor volume and the organ at risks (OARs) [Table 3]
  2. The DVH curves of different organs in the two techniques are shown in [Figure 2]. Each color in every diagram indicated a target or OARs.
Figure 2: The dose-volume histogram curves of different organs in technique 1 (a) and technique 2 (b)

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Table 3: Average absorbed dose in the interest organs and tumor volume resulted from treatment planning system

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Based on the TPS data, the homogeneity indexes of CTV and PTV of the two techniques (ΔD5%–95%) were calculated. They were 19.67 Gy and 3.50 Gy for CTV and PTV of technique 1, respectively. Corresponding values for technique 2 were 19.23 Gy and 3.36 Gy.

Comparisons of the two techniques, using Paired sample t-test, are summarized in Tables 2 and 3.


 > Discussion Top


Modern methods in whole CNS tumors radiotherapy such as IMRT and IMPT allow the delivery of the prescribed dose to a small target volume while minimizing the dose delivered to the surrounding critical normal organs. CSI is a very important element in treating cerebrospinal tumors. Every effort should be made to decrease the radiotherapy related side effects, especially with the currently available three-dimensional (3D) conformal radiotherapy planning system.

Target volume definition, sparing of critical normal structures, dose homogeneity, and fields junction arrangement have all been problematic in CSI and are especially critical in pediatric cases.[10] Using sophisticated methods such as IMRT and IMPT decrease the problems. However, in radiotherapy centers which are not equipped with this modern equipment, applying electron beams may dissolve the difficulties.

This dosimetric study was conducted to report the results of the measurement of doses received by target volumes and organs at risk during treatment of cerebrospinal tumors in the Rando phantom treated with CSI. Furthermore, two techniques, containing electron and photon beams in the treatment of spinal, which are executed, using conventional radiotherapy equipment, were compared.

As regards the target volume, the measurement and calculation data revealed that the two techniques provided acceptable coverage of the target volume. Based on the TPS data, the homogeneity indexes of CTV and PTV of the two techniques (?D5%–95%) were calculated, and similar results were obtained in both techniques. Considering the total administered dose to the CTV was 36 Gy and that which is administered to the PTV is 54 Gy, the median of dose received by the brain and spinal with calculated by TPS in the technique 1 was 36.8 and 36.54 Gy and in the technique 2 was 36.37 and 36.11 Gy, respectively. These results are closely related to the results published by Darunee Tongwan in his dosimetric analysis of CSI in comparing four different techniques, where the median dose received by the brain was 36.91 Gy and the median dose received by the spine was 38.12 Gy.[11]

As regards organs at risk, starting with the chiasma, dose received by the chiasma for two techniques was almost equal and similar to CTV dose. The chiasma dose in both techniques was lower than tolerance dose.[12]

Considering the mandible, the dose measured by the mandible in the technique 2 was very lower than the technique 1 (3.64 Gy vs. 11.22 Gy). Of course, mandible dose in two techniques was lower than tolerance dose; it may be due to head extension.

The total absorbed dose by the thyroid gland in the technique 1 was 25.31Gy at the end of the radiotherapy that this is different from results of Baghani et al. (16.64 Gy), of course thyroid dose in the technique 2 was very lower than the technique 1 (1.79 Gy vs. 25.31 Gy). The thyroid disorders caused by the direct radiation may vary. Regardless of thyroxin being increasing or decreasing, the cases of disorder tend to occur when the absorbed dose by the thyroid is between 15 and 50 Gy.[13] Although the absorbed dose by this organ even in the technique 1 does not exceed 50 Gy, it fell in the various range of the thyroid disorders. Up to one-third of patients develop primary hypothyroidism after CSI.[9],[14],[15] Reduction in this damage was observed when the thyroid gland was spared from the exit dose of the spinal field.[14] In study of Chojnacka et al., in the photon-based technique, the thyroid was spared by adopting two oblique fields in this region. The dose was reduced from 12 to 7 Gy when 35 Gy was applied for the spine.[16]

Jakacki et al. described cardiac toxicity in children who received CSI for medulloblastoma.[13] Spinal irradiation can deliver a significant exit dose to the heart. A relatively large percentage of the heart is in the beam path, especially when CSI is delivered using conventional 2D technique. In analysis of Chojnacka et al., in photon plans, the dose to the heart was nearly doubled compared to electron plans. Average doses for the heart were 17.5 Gy vs. 10 Gy, respectively, when 35 Gy was applied for the spine.[16] This is closely in accordance with our results that the mean absorbed dose received by the heart in the technique 1 and technique 2 was 20.79 Gy versus 1.11 Gy. Parker et al. also reported that in the IMRT plans, <1% of the heart volume was irradiated to doses above 15 Gy versus 46% for 3D CRT plans.[17]

In this study, the average of the mean dose received by the right and left lungs in the technique 1 was 7.57 and 7.79 Gy and in the technique 2 was 1.75 and 2.85 Gy. In both lungs and two techniques, lungs' dose was lower than tolerance dose. These results do not match with results of Chojnacka. They concluded that the use of photons or electrons for the spinal fields did not produce any detectable difference in pulmonary toxicity, and in the photon plans, the dose was slightly lower than in electron plans. Studies of pulmonary function after CSI rarely have been undertaken, perhaps because of the small volume of lung included in spinal field.[16]

Despite the superiority of technique 2 for reduction in most organs at risk, due to applying an anteriorly lumbar field, kidneys' dose in technique 2 was more than in technique 1. Kidney dose would be less and acceptable, provided electron beams with higher energy were applied, such as the study of Xiang Mu et al. in which, different results were obtained. They compared four techniques together in CSI with pediatric phantom and observed that the kidneys dose decreased with the electron plan.[18] Perhaps, this difference is due to the use of adult phantom in our study.

In accordance with predictions, OARs were spared with electron beams more efficiently than photon beam (P < 0.05). The results of comparison between two techniques in this research have a good accordance with the research by Hood et al.[19]

Although the IMRT is an approved clinical method with more accurate results and less damage to nearby tissue, there are some centers which do treatment with conventional methods. Hence, the results achieved in this study can be used as a simple method for those centers which do not have IMRT.


 > Conclusions Top


As a whole, the results revealed that electron beam was superior to photon beam in regard to dose reduction in organs at risk. If electron beam with higher energy was available, the dose received by kidney would be less. It is predicted that the pediatric kidney dose is not as high since without an anterior lumbar field, dose homogeneity in target volume would be acceptable. Therefore, it is suggested in radiotherapy centers where conventional techniques are employed; electron beam therapy would be the first choice for whole CNS radiotherapy.

Acknowledgment

This article is based on the data extracted from the M.Sc., desecration Code No. A-878 presented to the Medical Physics Department of Mashhad University of Medical Sciences. The authors would like to thank Emam Reza Hospital for their sincere co-operation without which completion of this work was not easily possible.

Financial support and sponsorship

Mashhad University of Medical Sciences (Mashhad, Iran) has financially supported the work.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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Jakacki RI, Goldwein JW, Larsen RL, Barber G, Silber JH. Cardiac dysfunction following spinal irradiation during childhood. J Clin Oncol 1993;11:1033-8.  Back to cited text no. 3
    
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Chin D, Sklar C, Donahue B, Uli N, Geneiser N, Allen J, et al. Thyroid dysfunction as a late effect in survivors of pediatric medulloblastoma/primitive neuroectodermal tumors: A comparison of hyperfractionated versus conventional radiotherapy. Cancer 1997;80:798-804.  Back to cited text no. 4
    
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Constine LS, Woolf PD, Cann D, Mick G, McCormick K, Raubertas RF, et al. Hypothalamic-pituitary dysfunction after radiation for brain tumors. N Engl J Med 1993;328:87-94.  Back to cited text no. 5
    
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Mulhern RK, Kepner JL, Thomas PR, Armstrong FD, Friedman HS, Kun LE, et al. Neuropsychologic functioning of survivors of childhood medulloblastoma randomized to receive conventional or reduced-dose craniospinal irradiation: A Pediatric Oncology Group Study. J Clin Oncol 1998;16:1723-8.  Back to cited text no. 6
    
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Grau C, Overgaard J. Postirradiation sensorineural hearing loss: A common but ignored late radiation complication. Int J Radiat Oncol Biol Phys 1996;36:515-7.  Back to cited text no. 7
    
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Wong FL, Boice JD Jr., Abramson DH, Tarone RE, Kleinerman RA, Stovall M, et al. Cancer incidence after retinoblastoma. Radiation dose and sarcoma risk. JAMA 1997;278:1262-7.  Back to cited text no. 8
    
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Paulino AC. Hypothyroidism in children with medulloblastoma: A comparison of 3600 and 2340 cGy craniospinal radiotherapy. Int J Radiat Oncol Biol Phys 2002;53:543-7.  Back to cited text no. 9
    
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Parker WA, Freeman CR. A simple technique for craniospinal radiotherapy in the supine position. Radiother Oncol 2006;78:217-22.  Back to cited text no. 10
    
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Tongwan D, Peerawong T, Oonsiri S, Shotelersuk K. Craniospinal irradiation in the supine position: a dosimetric. Asian Biomed 2009;3:699-708.  Back to cited text no. 11
    
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Emami B, Lyman J, Brown A, Coia L, Goitein M, Munzenrider JE, et al. Tolerance of normal tissue to therapeutic irradiation. Int J Radiat Oncol Biol Phys 1991;21:109-22.  Back to cited text no. 12
    
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Halperin EC, Perez CA, Brady LW. Perez and Brady's Principles and Practice of Radiation Oncology. 5th ed. USA: Wolters Kluwer Health; 2008.  Back to cited text no. 13
    
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Corrias A, Einaudi S, Ricardi U, Sandri A, Besenzon L, Altare F, et al. Thyroid diseases in patients treated during pre-puberty for medulloblastoma with different radiotherapic protocols. J Endocrinol Invest 2001;24:387-92.  Back to cited text no. 14
    
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Fossati P, Ricardi U, Orecchia R. Pediatric medulloblastoma: Toxicity of current treatment and potential role of protontherapy. Cancer Treat Rev 2009;35:79-96.  Back to cited text no. 15
    
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Chojnacka M, Skowronska-Gardas A, Morawska-Kaczynska M, Zygmuntowicz-Pietka A, Pedziwiatr K, Semaniak A, et al. Craniospinal radiotherapy in children: Electron- or photon-based technique of spinal irradiation. Rep Pract Oncol Radiother 2010;15:21-4.  Back to cited text no. 16
    
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Parker W, Filion E, Roberge D, Freeman CR. Intensity-modulated radiotherapy for craniospinal irradiation: Target volume considerations, dose constraints, and competing risks. Int J Radiat Oncol Biol Phys 2007;69:251-7.  Back to cited text no. 17
    
18.
Mu X, Björk-Eriksson T, Nill S, Oelfke U, Johansson KA, Gagliardi G, et al. Does electron and proton therapy reduce the risk of radiation induced cancer after spinal irradiation for childhood medulloblastoma? A comparative treatment planning study. Acta Oncol 2005;44:554-62.  Back to cited text no. 18
    
19.
Hood C, Kron T, Hamilton C, Callan S, Howlett S, Alvaro F, et al. Correlation of 3D-planned and measured dosimetry of photon and electron craniospinal radiation in a pediatric anthropomorphic phantom. Radiother Oncol 2005;77:111-6.  Back to cited text no. 19
    


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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