|Ahead of print publication
Dosimetric comparison of single-arc/partial-arc volumetric modulated arc therapy and intensity-modulated radiotherapy for peripheral and central lung cancer
Melek Akcay, Durmus Etiz, Kerem Duruer, Ozge Bozdogan, Alaattin Ozen
Department of Radiation Oncology, Medical Faculty of Osmangazi University, Eskisehir, Turkey
|Date of Submission||31-Mar-2019|
|Date of Decision||19-May-2019|
|Date of Acceptance||18-Oct-2019|
|Date of Web Publication||19-Oct-2020|
Department of Radiation Oncology, Medical Faculty of Osmangazi University, Odunpazari Eskisehir
Source of Support: None, Conflict of Interest: None
Aim: The aim of this study is to compare the differences between intensity-modulated radiotherapy (IMRT) and single-arc/partial-arc volumetric modulated arc therapy (SA/PA-VMAT) techniques in locally advanced-stage non-small cell lung cancer (NSCLC).
Materials and Methods: Locally advanced 22 patients with NSCLC were evaluated retrospectively. Each patient underwent radiation therapy with either IMRT or SA-VMAT or 2PA-VMAT technique. Homogeneity index, conformity number, and dosimetric parameters were evaluated.
Results: Ten peripheral and 12 central lung tumors were evaluated. In the entire patient group, tV5-10-60, total mean lung dose (tMLD), iV5-10-30-50-60, iMLD, and esophagus Dmean and Dmax were lower in IMRT technique, cV5-10-20-30, kMLD, and medulla spinalis Dmax were lower in PA-VMAT technique, whereas iMLD is the highest in the SA-VMAT technique. In peripheral tumors, tV5-10-60, iV5-10-20-30-40-60, iMLD, and esophagus Dmean were lower in IMRT technique and kV5-10 was lower in the 2PA-VMAT technique. In central tumors, tV5-10, tMLD, iV5-60, iMLD, and esophagus Dmean and Dmax were lower in IMRT technique, whereas cV10-20 and medulla spinalis Dmax were lower in 2PA-VMAT, and all contralateral lung doses are high in the SA-VMAT technique (all P < 0.05).
Conclusion: IMRT and VMAT techniques have different advantages in locally advanced lung cancer, and the use of those two techniques as a hybrid can provide a single collection of these advantages.
Keywords: Central lung cancer, dosimetry, intensity-modulated radiotherapy, peripheral lung cancer, volumetric modulated arc therapy
|How to cite this URL:|
Akcay M, Etiz D, Duruer K, Bozdogan O, Ozen A. Dosimetric comparison of single-arc/partial-arc volumetric modulated arc therapy and intensity-modulated radiotherapy for peripheral and central lung cancer. J Can Res Ther [Epub ahead of print] [cited 2021 Dec 5]. Available from: https://www.cancerjournal.net/preprintarticle.asp?id=298615
| > Introduction|| |
Radiotherapy (RT) plays a very important role in the treatment of non-small cell lung cancer (NSCLC). In recent years, more modern radiation techniques have emerged with the development of RT equipment and radiation physics. It is important to choose the most appropriate RT technique for patients with NSCLC. Intensity-modulated RT (IMRT) in combination with image-guided RT (IGRT) resulted in excellent clinical outcomes. Although IMRT increases the dose conformity, it requires longer treatment time. Volumetric modulated arc therapy (VMAT) significantly improved treatment time. Many studies have shown that VMAT technique provides high-level conformal dose distribution, decreases risky organ doses, and shortens the duration of treatment than IMRT. The long duration of treatment in IMRT may improve patient discomfort during treatment, and the increased monitor units (MUs) could lead to increased incidence of radiation-related secondary cancers., However, the low-dose lung volume (V5 and V10) increases with the VMAT technique. Dose-volume histogram (DVH) parameters V5 and V10 have been shown to be the predictors of radiation pneumonitis (RP).
Although all modern RT techniques provide appropriate dose distribution and reduce the risk of organ damage, there is still no consensus on optimal RT technique in NSCLC. In this dosimetric study, patients with NSCLC were treated with conventional fractionated RT.
The aim of the present study was to compare IMRT and single-arc (SA)/2 partial-arc (PA)-VMAT in irradiation of peripheral and central lung tumors. Furthermore, target volume coverage, organs at risk doses, and treatment duration were also compared.
| > Materials and Methods|| |
The study included 22 NSCLC patients, i.e., 10 with peripheral NSCLC and 12 with central NSCLC. All underwent radical RT ± chemotherapy (CT) in the Radiation Oncology Department of Eskişehir Osmangazi University Medical Faculty between 2016 and 2018. All diagnoses were confirmed histopathologically. Patients with peripheral and central lung cancer were randomly selected. All patients were staged according to the 8th edition staging system of the American Joint Committee on Cancer.
Target volume delineation and organs at risk
The patients were immobilized in the supine position with their arms raised above the head on a lung board (T-bar/Wingboard) specifically designed for lung treatments. A 5-mm slice thickness of images between the cricoid cartilage and the upper limit of the L2 vertebra was performed with the Siemens Somatom Definition AS ® CT device. Central tumors included bronchial tumor/perihilar masses. There was no elective nodal irradiation (ENI), and involved-field radiation therapy (IFRT) was used.
Primary lung tumor and lymph nodes with CT axis ≥1 cm or hypermetabolic in positron emission tomography– Computed tomography (CT) are contoured as gross tumor volume (GTV). Clinical target volume (CTV) typically encompasses the GTV plus 0.6–0.8 cm margin for tumor and 0.5 cm for affected lymph nodes. For the planning target volume (PTV), a 0.5-cm margin was added to the CTV. All contours were contoured together by three radiation oncologists.
Lungs, heart, esophagus, and medulla spinalis were contoured. Normal lung was formed by removal of GTV after both lungs were contoured. The planning organ at risk volume was extended as 5 mm to the spinal cord. The limits for the organs at risk in the present study are listed in [Table 1]. All generated plans for each patient consisted of 60 Gy to be delivered to PTV in 30 fractions. The planning was made to give at least 95% of PTV with a dose range not exceeding −5% and +5% of the prescribed dose. These plans were made by two physicists. Patients were treated with Varian Trilogy ® linear accelerator.
All patients underwent radiation therapy with either IMRT or SA-VMAT or PA-VMAT technique. All plans were calculated using the AAA algorithm in the Eclipse planning system (Version 13.0.26, Varian Medical Systems, Palo Alto, CA, USA), and 6 MV photon energy was chosen in all plans.
Dynamic IMRT was used. For each plan, 5 or 7 coplanar beams at different angles were used depending on the tumor location, tumor dose coverage, and organs at risk (5 coplanar beams in 11 patients and 7 coplanar beams in 11 patients). Sliding window method was used in all plans. There was no limitation on the total number of segments, the number of iterations, and the minimum MU per se gment. For each plan, 115 and 145 segments were used on 5 and 7 coplanar beams, respectively.
Single-arc volumetric modulated arc therapy
The SA-VMAT technique used a 360° single arc consisting of 178 control points. The rotation direction of the gantry was selected clockwise (CW). The starting angle was 181° and the ending angle was 179°. The collimator angle was chosen as 30° to reduce leakage radiation and tongue and groove effect in all plans. The gantry rotation rate was chosen to be a maximum of 4.8°/s with a dose rate of maximum 600 MU/min. These values were automatically set at gantry rotation.
Partial-arc volumetric modulated arc therapy
In PA-VMAT technique, two half arcs of 180° each consisting of 98 control points were used. Partial arcs were adjusted CW or counterclockwise according to the location of the tumor, and the starting angle of CW arc was 0°–10° and the end angle was 180°–190°. On the other hand, the starting angle of counterclockwise arc was 0°–350° and the end angle was 180°–170°. The collimator angle was chosen to be 30° in CW direction and 330° counterclockwise to reduce leakage radiation and tongue and groove effect in all plans. The gantry rotation rate was chosen to be a maximum of 4.8°/s with a dose rate of maximum 600 MU/min. These values were automatically set at gantry rotation.
Evaluation of dose-volume histogram
DVH for PTV, normal lung, ipsilateral lung, heart, medulla spinalis, and esophagus was examined in each technique. To determine the accuracy of the dose distribution on PTV, homogeneity index (HI) and conformation number conformation number (CN).
HI is defined as in the followed:
D2% is defined as the maximum dose given to 2% of the target volume. D98% is defined as the minimum dose given to 98% of the target volume, and D50% is defined as the median absorbed dose given to 50% of the target volume.
CN is calculated as in the followed:
TVRI is the target volume covered by the reference isodose. TV is the target volume and VRI is the volume covered by the reference isodose.
The CN value is between 0 and 1, with 1 as an ideal value. A HI value equal to 0 is an almost homogeneous dose distribution. Large HI values indicate higher doses than the defined dose and/or a large volume in the target receives a low dose.
The analyses were performed using SPSS for Windows 21.0 (IBM Corp. Released 2013. IBM SPSS Statistics for Windows, Version 22.0. Armonk, NY, USA: IBM Corp.). The Shapiro–Wilk test was used to investigate the appropriateness of the data to normal distribution. Nonparametric Friedman test was used in the comparison between planning groups, and Post hoc tests were used to determine different groups. Data were summarized as mean ± standard deviation or median (Q1; Q3). P <0.05 was considered statistically significant.
| > Results|| |
A total of 22 locally advanced-stage lung cancer patients were evaluated. IMRT, SA-VMAT, and 2PA-VMAT were planned for each patient. Patient and tumor characteristics are summarized in [Table 2]. Isodose curves from all three plans of each patient with central tumor are shown in [Figure 1] and with peripheral tumor in [Figure 2] in transverse sections.
|Figure 1: Isodose distribution of central tumor: (a) Intensity-modulated radiotherapy, (b) single-arc volumetric modulated arc therapy, (c) 2 partial-arc volumetric modulated arc therapy|
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|Figure 2: Isodose distribution of peripheral tumor: (a) Intensity-modulated radiotherapy, (b) single-arc volumetric modulated arc therapy, (c) 2 partial-arc volumetric modulated arc therapy|
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Organs at risk results in all patients
[Table 3] summarizes IMRT and VMAT DVHs in all patients. For the whole lung, in the IMRT plan, tV5 (38.7% vs. 40.1% and 43.1%), tV10 (22.6% vs. 24.1% and 30.5%), tV60 (0.2% vs. 0.6% and 0.5%), and tMLD (8.5 vs. 8.8 and 10.2 Gy) were the lowest compared to the 2PA-VMAT and SA-VMAT plans. For the ipsilateral lung, in the IMRT plan, iV5 (45.1% vs. 48.9% and 47.3%), iV10 (36.9% vs. 38.9% and 40.9%), iV30 (16.8% vs. 17.4% and 20.0%), iV50 (6.6% vs. 7.0% and 7.5%), and iV60 (0.2% vs. 1.3% and 1.4%) were lower compared to 2PA-VMAT and SA-VMAT plans. While there was no statistical difference between iV40 and iMLD in the IMRT and SA-VMAT plans, iV40 (12.1% vs. 10.5% and 10.8%) and iMLD (14.6 vs. 13.2 and 13.6 Gy) were higher in the 2PA-VMAT plans. In the contralateral lung, cV5 (32.4% vs. 33.3% and 38.4%), cV10 (10.8% vs. 11.6% and 23.3%), cV20 (0.7% vs. 2.4% and 3.2%), cV30 (0.1% vs. 1.1% and 0.3%), and cMLD (4 vs. 4.2 and 5.5 Gy) were lower in the 2PA-VMAT plans compared to IMRT and SA-VMAT plans. Medulla spinalis Dmax (maximum dose) (26.7 vs. 29.5 and 32.7 Gy) were lower in 2PA-VMAT plans than IMRT and SA-VMAT plans. Esophagus Dmean (mean dose) (10.3 vs. 11.9 and 10.6 Gy) and esophagus Dmax (40.0 vs. 43.9 and 42.5 Gy) were lower in IMRT plans than SA-VMAT and 2PA-VMAT plans.
These results suggest that the ipsilateral lung, total lung, and esophagus are better preserved with IMRT, whereas the contralateral lung and medulla spinalis are better preserved with 2PA-VMAT technique.
Organs at risk results in patients with peripheral tumor
[Table 4] summarizes IMRT and VMAT DVHs in peripheral lung cancer. For the whole lung, in the IMRT technique, compared to the SA-VMAT and 2PA-VMAT techniques, tV5 (25.8% vs. 31.1% and 27.2%), tV10 (13.3% vs. 19.3% and 15.9%), and tV60 (0% vs. 0.3% and 0.5%) were lower. In the ipsilateral lung, iV5 (33.9% vs. 35% and 37.9%), iV10 (24.3% vs. 27.6% and 29.9%), iV20 (16.7% vs. 18% and 20%, 6), iV30 (10.4% vs. 11.7% and 13.6%), iV40 (7% vs. 7.7% and 9%), iV60 (0.1% vs. 0.7% and 1.1%), and iMLD (9.1 vs. 9.8 and 10.8 Gy) were lower in IMRT plans than SA-VMAT and 2PA-VMAT. In contralateral lung, cV5 (16.8% vs. 21.6% and 27.1%) and cV10 (3.0% vs. 5.8% and 10.2%) were lower in the 2PA-VMAT than IMRT and SA-VMAT. Esophagus Dmean (6 vs. 6.5 and 7.5 Gy) was lower in IMRT than SA-VMAT and 2PA-VMAT.
In the peripheral tumors, total lung, ipsilateral lung, and esophagus were better preserved by IMRT technique, whereas the contralateral lung was better protected by 2PA-VMAT technique.
Organs at risk results in patients with central tumor
In [Table 5], IMRT and VMAT DVHs are summarized in central lung cancer. For the whole lung, in the IMRT plans, tV5 (49.4% vs. 50.9% and 52.9%), tV10 (30.3% vs. 31% and 39.9%), and tMLD (10.3 vs. 10.8 vs. 13.1 Gy) were the lowest, while they were found to be the highest in the SA-VMAT plans. For ipsilateral lung, iV5 (54.5% vs. 57% and 58%), iV60 (0.3% vs. 1.8% and 1.6%), and iMLD (16.6 vs. 16.8 and 17.8 Gy) were found to be the lowest in IMRT plans. iV20 (35.5% vs. 36.5% and 39.5%) was lower in the SA-VMAT technique compared to other techniques, whereas iV30 (25.3% vs. 22.1% and 22.5%) in 2PA-VMAT technique was higher than that. In contralateral lung doses, kV5 (43% vs. 47.8% and 45.4%) was lower in the IMRT technique, whereas kV10 (15.9% vs. 32.9%) and kV20 (1.4% vs. 2.8% and 5.3%) were lower in the 2PA-VMAT. All contralateral lung doses, especially cMLD (7.2 vs. 5.4 and 5.4 Gy), were higher in SA-VMAT technique than in others. Medulla spinalis Dmax (27.9 vs. 29.8 and 32.5 Gy) was lower in 2PA-VMAT and esophagus Dmean (13.8 vs. 15.5 and 14.1 Gy) and esophagus Dmax (51.2 vs. 54.5 and 54.8 Gy) were lower in IMRT plans.
In central tumors, total and ipsilateral lung and esophagus are preserved by IMRT, whereas 2PA-VMAT protects the contralateral lung and medulla spinalis.
Intensity-modulated radiotherapy and single-arc and 2 partial-arc volumetric modulated arc therapy techniques in patients with peripheral tumors: Monitor unit, CN, and homogeneity index
The comparative results of IMRT and VMAT techniques are summarized in [Table 6]. The MU values were higher in IMRT (657.95 ± 224.89) technique than SA-VMAT (466.10 ± 14.35) and PA-VMAT (454.70 ± 104.85) techniques. There was no statistically significant difference between the three techniques for HI. CN was significantly better in IMRT (0.86 ± 0.05) than SA-VMAT (0.83 ± 0.05) and 2PA-VMAT (0.78 ± 0.10) techniques.
|Table 6: Monitor unit, conformation number, and homogeneity index in peripheral tumors|
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Intensity-modulated radiotherapy and single-arc and 2 partial-arc volumetric modulated arc therapy techniques in patients with central tumors: Monitor unit, CN, and homogeneity index
The comparative results of IMRT and VMAT techniques are summarized in [Table 7]. The MU values were higher in IMRT (815.16 ± 244.03) technique than SA-VMAT (501.25 ± 51.97) and PA-VMAT (489.41 ± 61.29) techniques. There was no statistically significant difference between the three techniques for HI and CN.
|Table 7: Monitor unit, conformation number, and homogeneity index in central tumors|
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| > Discussion|| |
Lung cancer is the leading cause of cancer-related deaths, and standard treatment of locally advanced lung cancer is concomitant cytotoxic CT with RT. In the past, ENI was used in the treatment of locally advanced lung cancer, while at present, IFRT is performed. Accordingly, PTV has a more irregular shape and a complex structure. Providing the coverage of the complex target volume is also quite difficult with the old techniques.
In the past, locally advanced-stage NSCLC has been treated with three-dimensional conformal RT (3DCRT) and concurrent CT. However, currently, the use of IMRT and VMAT techniques has increased in lung cancer RT. Choosing the most appropriate RT technique in patients is important for both treatment efficacy and toxicity.
IMRT uses complex-modulated radiation beams shaping the radiation dose for target volumes with complex geometry and generates a sharper radiation gradient between the tumor and normal tissues compared to 3DCRT. According to dosimetry studies, IMRT reduces the doses of the organs at risk such as lung, heart, and esophagus and provides better dose distribution than 3DCRT. The clinical outcomes of IMRT with IGRT are quite good. When IMRT and VMAT are compared, the duration of MU and treatment is longer in IMRT. Many studies have compared IMRT and VMAT technique in lung cancer, but only a few studies compared IMRT and VMAT in central and peripheral lung cancer., Studies have shown that VMAT was superior to IMRT, especially in solid tumors with complicated target volumes.,,,
During the treatment of central tumor or mediastinal lymph node metastases, the esophagus is exposed to high-dose radiation. The esophagus requires lower doses due to its proximity to the medulla spinalis and the heart. Esophagus Dmax is associated with the development of esophagitis in many studies. Many studies have shown that esophagus Dmax >51 Gy during the treatment of lung cancer is associated with acute esophagitis.,, The Quantitative Analysis of Normal Tissue Effects in the Clinic report and the Radiation Therapy Oncology Group 0617 study recommend that the esophagus Dmean should be <34 Gy., The risk of acute esophagitis is associated with esophagus Dmax and Dmean.
In a study conducted by Jiang et al., 12 patients with locally advanced-stage lung cancer were evaluated. Esophagus V55 and Dmean were compared between IMRT, SA-VMAT, and PA-VMAT techniques, and although V55 and Dmean were higher in PA-VMAT technique, there was no statistically significant difference. The study by Wijsman et al. showed that when advanced-stage NSCLC patients were treated with IMRT or VMAT, only a limited increase of moderate-to-severe acute esophageal toxicity occurred after VMAT. In our study, IMRT technique has preserved the esophagus better.
RP is one of the most common side effects due to high radiation dose during thorax irradiation and can lead to increased morbidity and mortality. Many studies have demonstrated the association of RP with DVH parameters.,, Some of the dosimetric studies suggest that MLD is the most important factor in the development of RP.,, Some studies have shown the relationship between tV20 and tV30, especially in Grade 3–5 RP development., The study by Schallenkamp et al. showed that tV10-13-15 was associated with RP development. According to the study by Wang et al., tV5 is a parameter that increases the risk of ≥ Grade 2 RP. Ipsilateral lung doses are also important for RP development. Oetzel et al. reported no risk for RP if iMLD was <15 Gy; however, RP increased by 13% if iMLD was 17.5–20 Gy, 21% if iMLD was 22.5–25 Gy, and 43% if iMLD was 27.5 Gy. The study by Ramella et al. showed that iV20 >52%, iV30 >39%, and iMLD >22 Gy are risk factors for the development of RP. Furthermore, iV5 >65% is considered a risk factor for RP. A study performed by Song et al. showed that a contralateral cV5 ≥ 60% was a risk factor for ≥ Grade 3 RP. Thus, total, ipsilateral, and contralateral lung doses are important for the development of RP. In the present study, total and ipsilateral lungs were better preserved by IMRT, whereas the contralateral lung was better preserved by the PA-VMAT technique. SA-VMAT technique was found to significantly increase the contralateral lung doses, especially in the central tumor group.
| > Conclusion|| |
All three techniques have advantages in lung cancer RT. The use of hybrid techniques can provide these advantages in the same RT plan. Further studies are needed to support this idea.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]