|Ahead of print publication
Impact of 6 MV photons and mixed beam (6 MV and 15 MV) photons on the dose distribution in high-grade gliomas using three-dimensional conformal radiotherapy technique
Sachin Taneja1, Kirti Tyagi2, Deboleena Mukherjee2, Arti Sarin3
1 Associate Professor, Radiation Oncology, INHS Asvini, Colaba, Mumbai, Maharashtra, India
2 Medical Physicist, Department of Radiation Oncology, INHS Asvini, Colaba, Mumbai, Maharashtra, India
3 Professor and Consultant, Radiation Oncology, INHS Asvini, Colaba, Mumbai, Maharashtra, India
|Date of Submission||04-Feb-2020|
|Date of Decision||06-Mar-2020|
|Date of Acceptance||24-Apr-2020|
|Date of Web Publication||02-Sep-2020|
Department of Radiation Oncology, INHS Asvini, Institute of Naval Medicine, Colaba, Mumbai - 400 005, Maharashtra
Source of Support: None, Conflict of Interest: None
Background and Aim: The present study focused on the impact of 6 MV photons and mixed beam (6 MV and 15 MV) photons on dose distribution in high-grade gliomas using three-dimensional conformal radiotherapy (3DCRT) technique. The suitability of using different photon beam energies was evaluated with respect to dose distribution. Materials and Methods: A total of 24 patients of high-grade glioma treated on linear accelerator were enrolled and evaluated in this retrospective study. All patients had undergone total/subtotal resection of tumor. These patients were treated with postoperative adjuvant external beam radiotherapy on a linear accelerator using 3DCRT technique. Treatment plans were generated using 6 MV and a combination of both 6 MV and 15 MV photon beams. All plans were generated using suitable planning objectives, and dose constraints which were identical across the plans, except the beam energy. The plans were analyzed in terms of their target coverage, conformity, and normalized dose range. Results: In 16 patients out of 24, the treatment plans were generated using 6 MV photons, the normalization dose was well within 5%–7% of the dose prescribed. In the remaining 8 patients, the normalized dose was >107%, and in these cases, the use of mixed beam plans yielded a better dose distribution with normalized dose between 101% and 105%. Conformity index (CI) values were between 1.2 and 1.98. CI mean was 1.59. Conclusions: The use of mixed beams in 3DCRT technique may be considered as an alternative, especially in a scenario where pure 6 MV photons do not yield homogeneous dose distribution within the normalized range, and in centers where intensity-modulated radiation therapy and field-in-field technique are not available.
Keywords: Conformity index, glioma, mixed photon beam energy plans, organs at risk, three-dimensional conformal radiotherapy
|How to cite this URL:|
Taneja S, Tyagi K, Mukherjee D, Sarin A. Impact of 6 MV photons and mixed beam (6 MV and 15 MV) photons on the dose distribution in high-grade gliomas using three-dimensional conformal radiotherapy technique. J Mar Med Soc [Epub ahead of print] [cited 2020 Sep 19]. Available from: http://www.marinemedicalsociety.in/preprintarticle.asp?id=294198
| Introduction|| |
The fundamental principle in radiotherapy is to deliver maximum dose to the tumor and minimize the dose of radiation to normal tissue volumes. Three-dimensional conformal radiotherapy (3DCRT) in gliomas is a high-precision radiotherapy treatment, which entails patient immobilization, computed tomography (CT) and magnetic resonance imaging (MRI) for defining target volumes and organs at risks (OARs), treatment planning, verification, and delivery.,, The use of multileaf collimator (MLC) allows the possibility of shaping the isodose surfaces around the volume of interest (i.e. planning target volume [PTV]) in all three dimensions. 3DCRT is routinely used at most radiotherapy centers for the treatment of malignant gliomas and is the basic standard of care.
One of the challenges in radiation therapy is the selection of appropriate energy for performing a proper therapeutic plan and for delivering high-quality treatment., Selecting the appropriate energy for dose calculation depends on several factors such as tumor depth, homogeneity and heterogeneity of the tissue, density of tumor, and normal tissue that is located within the radiation beam's path.
The selection of the optimal energy and treatment plans with respect to PTV and dose to OARs such as brain stem, eye lens, optic nerve, optic chiasm, retina, pituitary, and temporal lobes using the above parameters is of paramount importance, and it affects the outcome and quality of life in these patients. In this study, we investigated the differences between dosimetric parameters from dose–volume histograms (DVHs) of the PTV and OARs in patients with high-grade gliomas planned, with pure 6 MV versus mixed beam (6 MV and 15 MV) in 3D conformal treatment plans. The total radiation dose prescription in high-grade gliomas is 59.4 Gy–60 Gy (1.8 Gy–2.0 Gy per fraction, 5 days a week).
The present study focused on the impact of 6 MV photons and mixed beam (6 and 15 MV) photons on dose distribution in high-grade gliomas using 3DCRT technique. The suitability of using different photon beam energies was evaluated with respect to the treatment site.
| Materials and Methods|| |
Twenty-four high-grade gliomas patients treated on linear accelerator were enrolled and evaluated in this retrospective study. Study population mainly comprised of patients referred from various dependent Armed Forces Hospitals spread across the country for treatment. Patients were mainly from rural background, and the male adult population dominated the study. Our study included 24 cases of intracranial high-grade gliomas who had undergone surgical resection. All patients had undergone total/subtotal resection of tumor, and the postoperative histopathological report confirmed the diagnosis. These patients were treated with postoperative adjuvant external beam radiotherapy on a linear accelerator using 3DCRT technique with concurrent and adjuvant chemotherapy. High-grade gliomas were treated to a dose of 59.4 Gy/33# to 60 Gy/30# (1.8 Gy/# to 2 Gy/#, 5# per week). The inclusion criterion of the study included (a) all high-grade gliomas postoperative, Karnofsky performance scores ≥70% at the time of screening; (b) life expectancy of >6 months, willingness to sign a written informed consent document; and (c) participant must have normal organ and bone marrow function within 30 days of study enrolment with leukocytes ≥3000/μL, absolute neutrophil count ≥1500/μL, platelets ≥1 lakh/μL, creatinine ≤1.4 mg/dL, BUN ≤20 mg/dL, and total bilirubin ≤1.0 mg/dL (SGPT [serum glutamic pyruvic transaminase]/SGOT] serum glutamic oxaloacetic transaminase] ≤2.5 × institutional upper limit of normal). Pregnant women, patients with Karnofsky performance score <70%, male/female <3 years of age, patients taking nucleoside analog, or being treated for Parkinsonism More Details were excluded from the study.
Simulation, target, and OARs delineation
All patients were immobilized using a custom-made thermoplastic mold in a neutral head and neck position to ensure positioning can be done in a reproducible manner for both planning and treatment. The patient is positioned in the CT scanner on a flat tabletop with the immobilization cast. Radiopaque fiducials were placed on the localization marks to identify the provisional isocenter location on the CT scans. Contrast-enhanced CT (CECT) scans of the brain for each patient were obtained in the treatment position using 16-slice CT (Siemens-Somatom Scope). CECT images of 3.0-mm slice thickness were obtained in axial, coronal, and sagittal planes for all patients. With the advent of multidetector CT, volume acquisition CT has become the norm. The advantage of acquiring volume acquisition CT is the ability to reconstruct the images in three different planes, that is, axial, sagittal, and coronal planes. CT-MR simulation was done for all the patients in a supine position. For image fusion, the Oncentra MasterPlan system (Nucletron – Elekta, The Netherlands) was used. Different registration techniques – manual, identity, landmark, surface matching, and mutual information (MI) are available for CT-MR fusion. MI is an automatic registration method that can be applied successfully to image series of different modalities and frames of reference. It is used in brain tumors because the region has a rigid frame (skull). The parameters used to check the accuracy of the fusion are eye lens, brain stem, and the skull.
Postoperative T1W contrast MRI axial images (3 mm), T2/flair MR axial images (3 mm) for anaplastic gliomas and glioblastoma multiforme were taken 3–4 weeks after surgery fused/coregistered with planning CECT images on treatment planning system – Oncentra (version 4.3). Slice-by-slice delineation of the gross target volume, clinical target volume, PTV, and organs at risk was done by radiation oncologists as per recommended guidelines.
Treatment objective, planning, and evaluation
The beam placements were done, and treatment plans were made with three fields: left lateral, right lateral, and vertex (couch rotated at 90°, gantry angle dependent on tumor and eye position, and kept between 20° and 70°). The MLCs were conformed to adequately cover the PTV and if required, wedges were also used [Figure 1]. Clinically, acceptable plans were generated on Oncentra (version 4.3) treatment planning system for energies 6 MV and combination of 6 MV and 15 MV.
|Figure 1: Beam placements and isodose distribution of patient planned with three-dimensional conformal radiotherapy|
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In radiotherapy centers, the doses to PTVs and OARs are assessed with treatment plans. The aim of planning is to cover the PTV with at least 95% of the prescribed dose. The plans generated were further evaluated with DVHs. DVHs may be constructed as differential DVHs and cumulative DVHs [Figure 2]. Organs at risk volumes were contoured, such as brain stem, lenses, optic nerves, optic chiasm, retina, pituitary, and temporal lobes. The dose constraints (Dmax values) followed for OARs were as per QUANTEC guidelines – retina <50 Gy, optic nerve <55 Gy, optic chiasm <55 Gy, brainstem <54 Gy, lenses <7 Gy, pituitary <45 Gy, cochlea <45 Gy, and temporal lobes <60 Gy. The most appropriate plan was selected for each patient.
|Figure 2: Cumulative dose–volume histogram of the patient with postoperative malignant gliomas|
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| Results|| |
Our study involved 24 cases of intracranial high-grade gliomas who had undergone surgical resection. All patients had undergone total/subtotal resection of tumor, and the postoperative histopathological reports confirmed the diagnosis and grade. These patients were treated with postoperative adjuvant external beam radiotherapy on a linear accelerator using 3DCRT technique with concurrent and adjuvant chemotherapy. [Table 1] summarizes the number of patients with gender, age along with the location of the tumor treated at this center. [Table 2] summarizes the volume of PTV and OARs. [Table 3] highlights the dosimetric variations between 6 MV and mixed beam (6 MV and 15 MV) in 3DCRT to critical structures. Conformity index (CI) is defined as the ratio of the volume of total tissue receiving at least 95% of the prescribed dose to the volume of PTV. CI values were found to be varying from 1.2 to 1.98, and the mean CI was 1.59.
|Table 2: Volume of planning target volumes and organs at risks of studied patients|
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|Table 3: Dosimetric variations between 6 MV and mixed beam (6 and 15 MV) photons in three-dimensional conformal radiotherapy to critical structures|
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| Discussion|| |
The 3DCRT technique as compared to two-dimensional treatment planning has shown tremendous improvement in dose distribution, local control of tumor, and decrease morbidity. Maximum safe surgical resection is the mainstay in the treatment of malignant high-grade gliomas and directly impacts the overall survival. Postoperative radiation and chemotherapy improve the progression-free survival in these patients [Figure 3]. The use of CT with MR fusion during radiotherapy planning has further resulted in defining the target volume and organs at risk with utmost precision. This has led to delivering high doses of radiation to the tumor with optimal coverage and minimizing the doses to the organs at risk, thereby reducing the late morbidity. In a study by Ashwatha N et al. analyzing 20 patients, the study showed intensity-modulated radiation therapy (IMRT) did not lead to significant improvement in target coverage (maximum dose, minimum dose, or D95 coverage) when compared to 3DCRT regardless of tumor location.,,,
|Figure 3: T1 contrast axial magnetic resonance imaging brain images (preoperative, postoperative, and postradiotherapy) depicting response in high-grade gliomas|
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In this study, we compared and evaluated the 3DCRT plans using dosimetric characteristics and analyzed the therapeutic plans with 6 and 15 MV photon beam energies on 24 patients. Plans using 6 MV photons and mixed beam (6 MV and 15 MV photons) were generated, and comparisons were carried out for a cohort of 24 patients. DVHs were calculated for target volume and organs at risk. Dose calculation in radiotherapy depends on various factors, including tumor depth, density of tumor, and normal tissue, that is, located on the radiation beam's path. The dose is normalized either to the isocenter or to a specific point other than the isocenter. External beam radiotherapy is carried out by more than one radiation beam to achieve a uniform/homogeneous dose distribution inside the target volume. Isodose curves are lines that joins points of equal dose. While isodose curves can be made to display the actual dose in Grays, it is more common to present them normalized to 95%–100% at a fixed point. Normalization at isocenter is done in most of the cases. The dose prescription was selected for 95% isodose levels. In 16 patients out of 24, the treatment plans were done using 6 MV, the normalization dose was well within 5% to 7% of the dose prescribed. In the remaining eight patients, the normalized dose was >107%, and in these cases, the use of mixed beam plans yielded a better dose distribution with normalized doses between 101% and 105%. Therefore, where the dose coverage with pure 6 MV photon beams was found to be inadequate, the use of mixed beam (6 MV and15 MV photons) may result in adequate and homogeneous target volume coverage with normalized dose within range (−5%–7% of the prescribed dose) and may be used as an option while planning 3D conformal radiotherapy, and in situ ations where IMRT and field-in-field (FIF) technique is not an option. It is, however, noted in our study that there was a slight increase in the dose to OARs with mixed beam plans versus pure beam photons, although the increase was within the dose constraints of QUANTEC guidelines.
According to RTOG guidelines defined to the quality of conformation, CI values between 1 and 2, the treatment is considered to comply with a treatment plan, an index between 0.9 and 1, 2 and 2.5 is considered to be a minor violation. Index value <0.9 or >2.5, the protocol violation considered to be acceptable. In our study, the CI values were between 1.2 and 1.98. The mean CI was 1.59. These results were found to be consistent with the study by Khaleel et al.
| Conclusions|| |
In our study, we have observed that optimal coverage of the target volume with homogeneous dose distribution was obtained for most of the patients using 6 MV photons with 3DCRT technique. In the remaining eight patients where optimal coverage of target volume could not be achieved using 6 MV photons, a combination of 6 MV and 15 MV photons (ipsilateral 6 MV photons, contralateral, and vertex 15 MV) yielded optimal target volume coverage within the normalized dose range of 101%–105%. However, organs at risk received a marginally higher dose with mixed beam, although they were within the dose constraints as specified by QUANTEC guidelines. The use of mixed beams in 3DCRT technique may be considered as an alternative, especially in a scenario where pure 6 MV photons have not yielded a homogeneous dose distribution within the normalized range, and in centers where IMRT and FIF technique is not available. We can conclude that the selection of ideal photon energy in radiotherapy leads to a better and more homogeneous dose–volume coverage and spares the organs at risk better.
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Conflicts of interest
There are no conflicts of interest
| References|| |
Morris DE, Bourland JD, Rosenman JG, Shaw EG. Three-dimensional conformal radiation treatment planning and delivery for low- and intermediate-grade gliomas. Semin Radiat Oncol 2001;11:124-37.
Tome WA, Meeks SL, Buatti JM, Bova FJ, Friedman WA, Li Z. A high-precision system for conformal intracranial radiotherapy. Int J Radiat Oncol Biol Phys 2000;47:1137-43.
Leibel SA, Sheline GE, Wara WM, Boldrey EB, Nielsen SL. The role of radiation therapy in the treatment of astrocytomas. Cancer 1975;35:1551-7.
Laughlin JS, Mohan R, Kutcher GJ. Choice of optimum megavoltage for accelerators for photon beam treatment. Int J Radiat Oncol Biol Phys 1986;12:1551-7.
Solderstrom S, Eklof A, Brahme A. Aspects on the optimal photon beam energy for radiation therapy. Acta Oncol 1995;38:179-87.
Shaw E, Arusell R, Scheithauer B, O'Fallon J, O'Neill B, Dinapoli R, et al
. Prospective randomized trial of low- versus high-dose radiation therapy in adults with supratentorial low-grade glioma: Initial report of a North Central Cancer Treatment Group/Radiation Therapy Oncology Group/Eastern Cooperative Oncology Group study. J Clin Oncol 2002;20:2267-76.
Jansen EP, Dewit LG, van Herk M, Bartelink H. Target volumes in radiotherapy for high-grade malignant glioma of the brain. Radiother Oncol 2000;56:151-6.
Bentzen SM, Constine LS, Deasey JO, Eisbruch A, Jackson A, et al
. Quantitative analysis of normal tissues effects in the clinic (QUANTEC): An introduction to the scientific issues. Int J Radiat Oncol Biol Phys 2010;76 3 Suppl: S3-9.
Brown TJ, Brennan MC, Li M, Church EW, Brandmeir NJ, Rakszawski KL, et al
. Association of the extent of resection with survival in glioblastoma: A systematic review and meta-analysis. JAMA Oncol 2016;2:1460-9.
van den Bent MJ, Afra D, de Witte O, Ben Hassel M, Schraub S, Hoang-Xuan K, et al
. Long-term efficacy of early versus delayed radiotherapy for low-grade astrocytoma and oligodendroglioma in adults: The EORTC 22845 randomised trial. Lancet 2005;366:985-90.
Ashwatha N, Josh Y, Sean B. Intensity modulated radiotherapy in high grade Glioma: Clinical and dosimetric results. Int J Radiat Oncol Biol Phys 2006;64:892-7.
MacDonald SM, Ahmad S, Kachris S, Vogds BJ, DeRouen M, Gittleman AE, et al
. Intensity modulated radiation therapy vs. 3 dimensional conformal radiation therapy in treatment of high grade gliomas: A dosimetric comparison. J Appl Clin Med Phys 2007;8:47-60.
Lorentini S, Amelio D, Giri MG, Fellin F, Meliado G, Rizzotti A, et al
. IMRT or 3D-CRT in glioblastoma? A dosimetric criterion for patient selection. Technol Cancer Res Treat 2013;12:411-20.
Thibouw D, Truc G, Bertaut A, Chevalier C, Aubignac L, Mirjolet C. Clinical and dosimetric study of radio therapy for Glioblastoma: Three-dimensional conformal radiotherapy versus intensity modulated radiotherapy. J Neurooncol 2018;137:429-38.
Feuvret L, Noël G, Mazeron JJ, Bey P. Conformity index: A review. Int J Radiat Oncol Phys 2006;64:333-42.
Khaleel IA, Govardhan HB, Kumar V. Comparison of intensity modulated radiation therapy and 3 dimension conformal radiotherapy (3DCRT) in supratentorial astrocytic series WHO grade III-IV primary malignant brain tumors. J Nucl Med Radiat Ther 2018;9:1000368.
[Figure 1], [Figure 2], [Figure 3]
[Table 1], [Table 2], [Table 3]