|Year : 2021 | Volume
| Issue : 1 | Page : 22-27
Dosimetric comparison of coplanar intensity-modulated radiotherapy, noncoplanar intensity-modulated radiotherapy, and volumetric arc therapy planning technique in hippocampal-sparing whole-brain radiotherapy
Ajay Vindhyachal Sharma, Priyusha Bagdare, Pranav Chadha, Pragya Shree, Mohini Gupta, Rajkumar Chauhan, Isha Jaiswal, Kaustav Talapatra
Department of Radiation Oncology, Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, Maharashtra, India
|Date of Submission||11-Sep-2020|
|Date of Decision||10-Feb-2021|
|Date of Acceptance||06-Apr-2021|
|Date of Web Publication||07-Jun-2021|
Ajay Vindhyachal Sharma
Kokilaben Dhirubhai Ambani Hospital and Medical Research Institute, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
The aim of this study was to compare the dosimetric parameters of Co-planar Intensity modulated radiotherapy (C-IMRT), non-coplanar (NC-IMRT), and volumetric arc therapy (VMAT) planning technique in hippocampal sparing (HS) whole brain radiotherapy (WBRT). Fifteen patients of brain metastasis (BM) treated with hippocampal sparing whole-brain palliative radiation were selected for this study. C-IMRT, NC-IMRT and VMAT plans were generated for the comparison. Generated plans were evaluated based on planning target volume (PTV) coverage, conformity index (CI), homogeneity index (HI), beam-on time (BOT) and dose delivered to organs at risk (OARs) for the prescribed dose (PD) of 30 Gy in 10 fractions. Statistically significant difference was found in PTVD95%, PTVmax, HI, BOT, MU, Dmax of the brainstem, Dmean of eyes, Dmax of lenses and Dmax, Dmean and D2% of the bilateral hippocampus. However, a non-significant difference was observed in CI, D100% of both the hippocampus, Dmax of the optic chiasm, optic nerves, and Dmax of eyes in all the three planning techniques. Considering the superior plan quality, both NC-IMRT and VMAT are better than the C-IMRT planning technique. Based on beam-on time and delivery efficiency VMAT is found to be superior to both the C-IMRT and NC-IMRT technique. Doses to OARs are very well within the limits in all the three planning techniques.
Keywords: Hippocampal sparing, intensity-modulated radiotherapy, volumetric arc therapy, whole brain
|How to cite this article:|
Sharma AV, Bagdare P, Chadha P, Shree P, Gupta M, Chauhan R, Jaiswal I, Talapatra K. Dosimetric comparison of coplanar intensity-modulated radiotherapy, noncoplanar intensity-modulated radiotherapy, and volumetric arc therapy planning technique in hippocampal-sparing whole-brain radiotherapy. Radiat Prot Environ 2021;44:22-7
|How to cite this URL:|
Sharma AV, Bagdare P, Chadha P, Shree P, Gupta M, Chauhan R, Jaiswal I, Talapatra K. Dosimetric comparison of coplanar intensity-modulated radiotherapy, noncoplanar intensity-modulated radiotherapy, and volumetric arc therapy planning technique in hippocampal-sparing whole-brain radiotherapy. Radiat Prot Environ [serial online] 2021 [cited 2021 Jun 24];44:22-7. Available from: https://www.rpe.org.in/text.asp?2021/44/1/22/317947
| Introduction|| |
Brain metastasis (BM) can be defined as the migration and colonization of tumor cells to brain parenchyma from a known or an unknown primary cancer and is the most common brain tumor in adults. In comparison to other sites of metastasis, the presence of BM in a cancer patient depicts poor progression-free survival, overall survival, and neurological functions. The increased global incidence of malignancy with improved systemic management with prolonged survival and increased central nervous system surveillance with accurate and sensitive imaging techniques such as magnetic resonance imaging (MRI) and magnetic resonance spectroscopy have contributed to a rise in brain metastatic disease.,,, BM can be categorized as solitary, single, or multiple lesions with respect to number and the primary/extracranial disease, or being precocious, synchronous, and metachronous with regard to timing of the presentation to the primary disease. There are varieties of treatment options for single BM in the form of conventional surgery, stereotactic radiosurgery, and/or whole-brain radiotherapy (WBRT),, however, the treatment options of multiple BMs are limited to WBRT typically administered over multiple sessions with a significantly poor prognostic outcome based on assessment models such as Radiation Therapy Oncology Group (RTOG)-Recursive Partitioning Analysis and Disease-Specific Graded Prognostic Assessment.
Investigating neurocognitive function (NCF) following WBRT has revealed toxicities in patients following brain radiotherapy (RT). The neurocognitive toxicity after brain irradiation has an early component and a late component., Early neurocognitive decline manifests as verbal dysfunction, spatial disorientation, and short-term memory loss and late component manifests as severe dementia, cognitive deterioration, and cerebellar dysfunction.,
Emerging evidence suggests that radiation injury to neural progenitor cells in the subgranular zone of the hippocampus mediated via apoptosis which is both sharp and prolonged leads to neurocognitive decline in terms of memory, learning, and spatial processing.,, To spare the hippocampus effectively, various RT techniques such as intensity-modulated RT (IMRT), volumetric arc therapy (VMAT), and helical tomotherapy are available., There are studies available on the dosimetric analysis of coplanar C-IMRT and VMAT planning techniques., The present study is based on the intercomparison of C-IMRT, noncoplanar (NC-IMRT), and VMAT planning techniques. Beam arrangements used in the present study for NC-IMRT employed non-coplanar couch angles and VMAT planning techniques employed split-arc components, which are different than the beam arrangements used in the previous quoted studies.,
| Materials and Methods|| |
Computed tomography simulation
In the present study, 15 palliative patients with brain metastases were selected for the treatment of hippocampal-sparing (HS) WBRT. A thermoplastic sheet (Orfit) was used for each patient to immobilize the site of interest. SOMATOM Scope Power (Siemens Medical Systems, Germany) was utilized for the computed tomography (CT) scan of the patients, and the CT images of 1-mm slice thickness were acquired for each patient in the supine position. The CT images fused with contrast-enhanced MRI T1 contrast 1-mm slice with no interslice width MRI were transferred to the Eclipse treatment planning system (TPS) version 13.6 (Varian Medical Systems, Palo Alto, CA, USA) for contouring and planning. The clinical tumor volume, planning target volume (PTV), and organs at risk (OARs) such as the brainstem, optic chiasm, optic nerves, eyes, and eye lenses were delineated on the CT images following the RTOG 0933 guidelines. Both the hippocampi were drawn, and a 5-mm margin was given from both the hippocampi to create the hippocampal avoidance regions. Plan evaluation was done on the total PTV drawn including the hippocampus regions. The volume of the targets was in the range from 1275.1 to 1978.8 cm3 with a mean volume of 1541.15 cm3. All the plans were executed for 30 Gy in ten fractions (#) with 3 Gy/# and five fractions per week. C-IMRT, NC-IMRT, and VMAT plans for all the cases were created on the same CT data set.
The major challenge which is associated with the various whole brain hippocampal sparing planning techniques is the island of low dose which gets created around both the hippocampii. In each planning technique the volume of this low dose island region varies, thus there is a consistent endeavor to achieve the minimum low dose island volume and minimum dose to the hippocampus along with the optimum target coverage. Keeping these objectives in mind treatment plans were generated for all the patients using three different RT techniques, namely C-IMRT, NC-IMRT, and VMAT. All the plans were generated on Eclipse TPS for EDGE linear accelerator (Varian Medical Systems, Palo Alto, CA, USA) equipped with flattening filter-free beams, high-definition multileaf collimator, 6-degree-of-freedom couch, and jaw tracking technology for the reduction in leakage and out-of-field dose. Each patient plan was generated for all the three techniques using 6 MV photon energy with 600 MU/min dose rate. All the planning and optimization parameters were kept the same for all the three techniques. The dose was calculated using Acuros XB version 13.6.23 (Varian Eclipse, Palo Alto, CA, USA) with a high-resolution calculation dose grid size of 2.5 mm. All the C-IMRT plans were done with nine coplanar (CP) fields with couch angle 0°, and no parallel-opposed fields were chosen. All the NC-IMRT plans were generated using nine noncoplanar beams with no parallel-opposed fields. Optimized couch angles were selected by making various plans on CT images of patients to achieve the desired objectives. All the VMAT plans were generated using four coplanar arcs. However, in VMAT keeping same concept in mind instead of using two full arcs with complete jaws opening, 4 arcs are used by closing less than half of the PTV region. A study done by Yuen et al. also explore and compare the two different arcs geometries forwhole brain hippocampus sparing radiotherapy. The isocenter was placed at the geometrical center of the PTV in all the three planning techniques. Beam arrangements for all the three planning techniques are shown in [Table 1].
|Table 1: Beam arrangements for coplanar intensity-modulated radiotherapy, noncoplanar intensity-modulated radiotherapy, and volumetric arc therapy planning technique|
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All plans generated were compared based on PTV coverage, conformity index (CI), homogeneity index (HI), beam-on time (BOT), and dose received by OARs referring to corresponding dose–volume histogram associated with each plan. CI and HI at 95% of the prescribed dose (PD) were calculated by using the following equations:
CI = Total volume receiving 95% of PD/PTV and HI = D5%/D95%
where PTV is the PTV and D95% and D5% are doses delivered to 95% and 5% of the PTV, respectively. Doses to OARs were compared based on RTOG 0933 trial.
Statistical analysis of the data was performed employing MS Excel and SPSS version 22.0 (IBM SPSS Statistics for Windows, Armonk, NY, USA). The normality of all data was verified by using the Kolmogorov–Smirnov (K-S) test. Analysis of variance (ANOVA) test was employed to determine the intergroup mean variance followed by Tukey's test (P < 0.05) for pair-wise comparison.
| Results|| |
Based on the study done on 15 patients, [Table 2] and [Table 3] represent the variation in PTV parameters and doses to OARs for C-IMRT, NC-IMRT, and VMAT planning techniques, respectively.
|Table 2: Variation in planning target volume parameters for coplanar intensity-modulated radiotherapy, noncoplanar intensity-modulated radiotherapy, and volumetric arc therapy planning technique|
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|Table 3: Variation in doses to organs at risks for coplanar intensity-modulated radiotherapy, noncoplanar intensity-modulated radiotherapy, and volumetric arc therapy planning technique|
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K-S test inferred a normal distribution of the dosimetry data (P = 0.02), henceforward ANOVA and Tukey's parametric tests were employed as mentioned prior.
Analysis done on the dose received by 95% of the target volume (PTVD95%) showed that there is a nonsignificant difference observed in case of NC-IMRT versus VMAT plans (P = 0.927), however, a significant difference was observed for C-IMRT versus NC-IMRT (P = 0.0) and C-IMRT versus VMAT (P = 0.0).
The maximum dose to PTV volume (PTVmax) was found to be nonsignificant in the case of NC-IMRT versus VMAT plans (P = 0.641), however, a significant difference was observed for C-IMRT versus NC-IMRT (P = 0.002) and C-IMRT versus VMAT (P = 0.018) inferring a higher dose PTVmax with NC-IMRT and VMAT.
A nonsignificant difference in HI was found for NC-IMRT versus VMAT plans (P = 0.992), whereas a significant difference was observed for C-IMRT versus NC-IMRT (P = 0.0) and C-IMRT versus VMAT (P = 0.0).
CI was found to be nonsignificant in NC-IMRT versus VMAT plans (P = 0.807), C-IMRT versus NC-IMRT (P = 0.143) plans, and C-IMRT versus VMAT (P = 0.401) plans.
A significant difference was observed in MU delivered and BOT for all the three techniques as it was also reported by Rong et al. in their study. A significant difference in MU delivered was found in NC-IMRT versus VMAT plans (P = 0.0), C-IMRT versus NC-IMRT (P = 0.0) plans, and C-IMRT versus VMAT (P = 0.0) plans, respectively. BOT was also found significant in NC-IMRT versus VMAT plans (P = 0) as well as for C-IMRT versus VMAT (P = 0). A nonsignificant difference in BOT was observed for C-IMRT versus VMAT (P = 0.858) plans.
A nonsignificant difference was observed in maximum dose (Dmax) received by left and right hippocampi in NC-IMRT versus VMAT plans (pleft = 0.969 and pright = 0.253), whereas a significant difference was observed for C-IMRT versus NC-IMRT plans (pleft = 0.0 and pright = 0.0) plans and C-IMRT versus VMAT (pleft = 0.0 and pright = 0.0) plans.
A nonsignificant difference was observed in mean dose (Dmean) received by left and right hippocampi in NC-IMRT versus VMAT plans (pleft = 0.766 and pright = 0.929); it was found to be significant in C-IMRT versus NC-IMRT plans (pleft = 0.0 and pright = 0.009) and C-IMRT versus VMAT plans (pleft = 0.001 and pright = 0.002).
Dose received by 2% volume of left hippocampus (D2%) was observed significant for all the three planning techniques (NC-IMRT and VMAT, pleft = 0.025; C-IMRT and NC-IMRT, pleft = 0.004; and C-IMRT and VMAT, pleft = 0.0). D2% of right hippocampus was observed significant for C-IMRT versus NC-IMRT (pright = 0.011) and C-IMRT and VMAT (pright = 0.010), whereas a nonsignificant difference was observed in NC-IMRT versus VMAT (pright = 0.999) plans.
A nonsignificant difference was observed in dose received by 100% volume (D100%) of both the hippocampi in NC-IMRT versus VMAT plans (pleft = 0.385 and pright = 0.989), C-IMRT versus NC-IMRT plans (pleft = 0.987 and pright = 0.949), and C-IMRT versus VMAT plans (pleft = 0.474 and pright = 0.985).
Dmean of both the eyes was found to be nonsignificant in C-IMRT versus VMAT plans (pleft = 0.60 and pright = 0.985), however, it was observed significant in C-IMRT versus NC-IMRT (pleft = 0.001 and pright = 0.022) plans and C-IMRT versus VMAT (pleft = 0.015 and pright = 0.033) plans.
A nonsignificant difference was found in all the three planning techniques for Dmax of the optic chiasm, optic nerves, and eyes in all the three planning techniques.
| Discussion|| |
WBRT is the gold standard treatment for brain metastasis that provides good local control & improvement in survival but at the cost of a decline in neurocognitive function because of damage to the hippocampus. Traditionally WBRT was planned with the German helmet technique which was a simple method to cover the entire brain. Outcome of WBRT suggests that damage to hippocampus during cranial irradiation contributes extensively to the development of neurocognitive decline, especially in memory-related domains. Advance conformal radiotherapy techniques such as IMRT and VMAT may spare patients some of the neurocognitive sequelae of cranial irradiation without considerably varying the therapeutic gain., In our study, three different conformal radiotherapy planning techniques were used to generate the patient's plan for dosimetric study in the whole brain hippocampus sparing
The results obtained by the current study indicate that VMAT and NC-IMRT were found to be superior with respect to PTV coverage and HI is found to be significantly higher than C-IMRT. Dose distribution obtained for one of the patients in C-IMRT, NC-IMRT, and VMAT planning techniques is shown in [Figure 1]a, [Figure 1]b, [Figure 1]c, respectively.
|Figure 1: Dose distribution in (a) coplanar intensity-modulated radiotherapy, (b) noncoplanar intensity-modulated radiotherapy, and (c) volumetric arc therapy planning technique|
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Regardless of the planning technique, statistical analysis demonstrated no significant difference in CI and doses received by OARs such as optic nerve, eyes, and eye lenses. As per defined by RTOG 0933 protocol, the Dmax for hippocampus should be ≤16 Gy and the D100% should be ≤9 Gy). In present study the Dmax and D100% for both the hippocampus were well within the tolerance limits for all the three planning techniques. The dominating parameters which make VMAT superior to NC-IMRT in our study are MU delivered and BOT. Time taken to deliver any VMAT plan was found to be less than NC-IMRT with less MU delivered. It plays a significant role in palliative patients' treatment and in the RT department where patients' load is high. It provides a higher patient throughput with minimal MU delivered with the minimum on-couch time, enhancing patient comfort and less probability of intrafraction errors.
| Conclusions|| |
Based on the current study, all the three planning techniques, namely C-IMRT, NC-IMRT, and VMAT, are equivalent as far as hippocampus sparing is concerned. The doses received by the hippocampus and OARs in all the three planning techniques are well within the tolerance limits. Both NC-IMRT and VMAT are superior to C-IMRT in terms of PTV target coverage and HI. VMAT is found to be superior to both C-IMRT and NC-IMRT techniques as it is the fastest and delivers a significantly lesser amount of monitor units.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Nayak L, Lee EQ, Wen PY. Epidemiology of brain metastases. Curr Oncol Rep 2012;14:48-54.
Larson DA, Rubenstein JL, McDermott MW. Metastatic cancer to the brain. In: DeVita VT Jr, Lawrence TS, Rosenberg SA, editors. DeVita, Hellman, Rosenberg's Cancer Principles and Practice of Oncology. 8th
ed. Philadelphia, PA: Lippincott Williams and Wilkins; 2008. p. 2461-75.
Fink KR, Fink JR. Imaging of brain metastases. Surg Neurol Int 2013;4:S209-19.
Rick JW, Shahin M, Chandra A, Dalle Ore C, Yue JK, Nguyen A, et al
. Systemic therapy for brain metastases. Crit Rev Oncol Hematol 2019;142:44-50.
Smedby KE, Brandt L, Bäcklund ML, Blomqvist P. Brain metastases admissions in Sweden between 1987 and 2006. Br J Cancer 2009;101:1919-24.
Sundström JT, Minn H, Lertola KK, Nordman E. Prognosis of patients treated for intracranial metastases with whole-brain irradiation. Ann Med 1998;30:296-9.
Gondi V, Hermann BP, Mehta MP, Tomé WA. Hippocampal dosimetry predicts neurocognitive function impairment after fractionated stereotactic radiotherapy for benign or low-grade adult brain tumors. Int J Radiat Oncol Biol Phys 2012;83:487-93.
Monje ML, Mizumatsu S, Fike JR, Palmer TD. Irradiation induces neural precursor-cell dysfunction. Nat Med 2002;8:955-62.
Gondi V, Tomé WA, Mehta MP. Why avoid the hippocampus? A comprehensive review. Radiother Oncol 2010;97:370-6.
Shors TJ, Miesegaes G, Beylin A, Zhao M, Rydel T, Gould E. Neurogenesis in the adult is involved in the formation of trace memories. Nature 2001;410:372-6.
Laack NN, Brown PD. Cognitive sequelae of brain radiation in adults. Semin Oncol 2004;31:702-13.
Caine C, Mehta MP, Laack NN, Gondi V. Cognitive function testing in adult brain tumor trials: Lessons from a comprehensive review. Expert Rev Anticancer Ther 2012;12:655-67.
Roman DD, Sperduto PW. Neuropsychological effects of cranial radiation: Current knowledge and future directions. Int J Radiat Oncol Biol Phys 1995;31:983-98.
Mizumatsu S, Monje ML, Morhardt DR, Rola R, Palmer TD, Fike JR. Extreme sensitivity of adult neurogenesis to low doses of X-irradiation. Cancer Res 2003;63:4021-7.
Ferrer I, Serrano T, Alcantara S, Tortosa A, Graus F. X-ray-induced cell death in the developing hippocampal complex involves neurons and requires protein synthesis. J Neuropathol Exp Neurol 1993;52:370-8.
Soehartati G, Hadi N, Mahesa A, Arie M, Wahyu W, Irwan R, et al
. Dosimetry analysis on IMRT, VMAT, and HT technique in hippocampal sparing whole brain radiotherapy. Oncol Radio 2019;46:058-63.
Rong Y, Evans J, Xu-Welliver M, Pickett C, Jia G, Chen Q, et al
. Dosimetric evaluation of intensity-modulated radiotherapy, volumetric modulated arc therapy, and helical tomotherapy for hippocampal-avoidance whole brain radiotherapy. PLoS One 2015;10:e0126222.
Canyilmaz E, Uslu GD, Colak F, Hazeral B, Haciislamoglu E, Zengin AY, et al
. Comparison of dose distributions hippocampus in high-grade gliomas irradiation with linac-based C-IMRT and volumetric arc therapy: A dosimetric study. Springerplus 2015;4:114-18.
Lee K, Lenards N, Holson J. Whole-brain hippocampal sparing radiation therapy: Volume-modulated arc therapy vs Intensity-modulated radiation therapy case study. Med Dosim 2016;41:1521.
Smyth G, Evans PM, Bamber JC, Mandeville HC, Welsh LC, Saran FH, et al
. Non-coplanar trajectories to improve organ at risk sparing in volumetric modulated arc therapy for primary brain tumors. Radiother Oncol 2016;121:124-31.
Yuen AH, Wu PM, Li AK, Mak PC. Volumetric modulated arc therapy (VMAT) for hippocampal-avoidance whole brain radiation therapy: Planning comparison with Dual-arc and Split-arc partial-field techniques. Radiat Oncol 2020;15:42.
Kazda T, Jancalek R, Pospisil P, Sevela O, Prochazka T, Vrzal M, et al
. Why and how to spare the hippocampus during brain radiotherapy: The developing role of hippocampal avoidance in cranial radiotherapy. Radiat Oncol 2014;9:139.
Oskan F, Ganswindt U, Schwarz SB, Manapov F, Belka C, Niyazi M. Hippocampus sparing in whole-brain radiotherapy. A review. Strahlenther Onkol 2014;190:337-41.
Gondi V, Pugh SL, Tome WA, Caine C, Corn B, Kanner A, et al
. Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): A phase II multi-institutional trial. J Clin Oncol 2014;32:3810-6.
[Table 1], [Table 2], [Table 3]