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Single-arc volumetric-modulated arc therapy (sVMAT) as adjuvant treatment for gastric cancer: Dosimetric comparisons with three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT)
Medical Dosimetry ] (2013) ]]]–]]]
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Single-arc volumetric-modulated arc therapy (sVMAT) as adjuvant treatment for gastric cancer: Dosimetric comparisons with three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) Xin Wang, M.D., Ph.D.,n,1 Guangjun Li, M.S.,† Yingjie Zhang, M.S.,† Sen Bai, Ph.D.,† Feng Xu, M.D.,n Yuquan Wei, M.D., Ph.D.,‡ and Youling Gong, M.D., Ph.D.‡ *Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, P.R. China; †Radiation Physics Center, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, P.R. China; and ‡Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, P.R. China
A R T I C L E I N F O
A B S T R A C T
Article history: Received 6 June 2012 Accepted 26 April 2013
To compare the dosimetric differences between the single-arc volumetric-modulated arc therapy (sVMAT), 3-dimensional conformal radiotherapy (3D-CRT), and intensity-modulated radiotherapy (IMRT) techniques in treatment planning for gastric cancer as adjuvant radiotherapy. Twelve patients were retrospectively analyzed. In each patient's case, the parameters were compared based on the dosevolume histogram (DVH) of the sVMAT, 3D-CRT, and IMRT plans, respectively. Three techniques showed similar target dose coverage. The maximum and mean doses of the target were significantly higher in the sVMAT plans than that in 3D-CRT plans and in the 3D-CRT/IMRT plans, respectively, but these differences were clinically acceptable. The IMRT and sVMAT plans successfully achieved better target dose conformity, reduced the V20/30, and mean dose of the left kidney, as well as the V20/30 of the liver, compared with the 3D-CRT plans. And the sVMAT technique reduced the V20 of the liver much significantly. Although the maximum dose of the spinal cord were much higher in the IMRT and sVMAT plans, respectively (mean 36.4 vs 39.5 and 40.6 Gy), these data were still under the constraints. Not much difference was found in the analysis of the parameters of the right kidney, intestine, and heart. The IMRT and sVMAT plans achieved similar dose distribution to the target, but superior to the 3D-CRT plans, in adjuvant radiotherapy for gastric cancer. The sVMAT technique improved the dose sparings of the left kidney and liver, compared with the 3D-CRT technique, but showed few dosimetric advantages over the IMRT technique. Studies are warranted to evaluate the clinical benefits of the VMAT treatment for patients with gastric cancer after surgery in the future. & 2013 American Association of Medical Dosimetrists.
Keywords: Gastric cancer Volumetric-modulated arc therapy Three-dimensional conformal radiotherapy Intensity-modulated radiotherapy Dosimetric comparison
Introduction Gastric cancer occurs with high incidence rate in West China. Although there are many protocols in managing of this type of disease, surgery remains as the key strategy of the treatment for the locally advanced gastric cancer. After operation, the locoregional relapse rate was nearly 30% to 50%, and almost half of these relapses were the only sites of the failures observed in clinical
Reprint requests to: Youling Gong, Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, P.R. China. Tel.: þ86 2885 423 581; fax: þ86 2885 424 619. E-mail: [email protected] 1 Dr. Xin Wang and Guangjun Li contributed equally to this work.
practice.1,2 As the results of the Gastric Surgical Adjuvant Trial Intergroup 0116 (INT 0116) were published, chemoradiotherapy was established as the standard adjuvant treatment for locoadvanced gastric cancer after surgery.3 In this landmark trial, adjuvant chemoradiotherapy improved the 3-year median survival to 36 months compared with 27 months in the surgery-alone group in T3/4 or N-positive patients with high-risk, resected gastric cancer. INT 0116 radiation therapy approach has involved 2-dimensional treatment planning, mostly with a standard anteroposteriorposteroanterior field arrangement. The consequences were obvious, giving rise to the side-effects that necessitated termination of the therapy in nearly 17% of patients.3 With the development of conformal radiotherapy, 3-dimensional conformal radiotherapy (3D-CRT) showed a superior dose distribution and normal tissue sparing, and became the routine application in radiotherapy treatment planning. As the
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Target delineation and dose prescription
Table 1 Basic and clinical characteristics of the studied patients (n ¼ 12) Age (y) Median Range Sex Male Female Disease stage II IIIA IIIB IV (M0) Tumor location Upper third Middle third Lower third Extent of node dissection D1 D2
57 43 to 70 7 5 2 3 5 2 4 4 4 2 10
implementation of the intensity-modulated radiotherapy (IMRT), the issue of whether the IMRT technique was better than the 3D-CRT technique as adjuvant treatment for gastric cancer has been discussed, and the conclusions have been considered as controversial.4–7 Volumetric-modulated arc therapy (VMAT), a rotational form of IMRT, has been introduced into clinical practice with other treatment methodologies recently, including lung cancers,8,9 prostate cancer,10 and anal cancer.11 Based on a number of studies, it has been pointed out that the VMAT technique might reduce the treatment time without compromising plan quality compared with IMRT in radiotherapy planning for different cancer types. In adjuvant treatment planning for gastric cancer, only one study focused on the dosimetric differences between IMRT and arc radiotherapy (tomotherapy), which indicated that tomotherapy was similar to the IMRT technique.4 Until now, no study has been published comparing the 3D-CRT, IMRT, and VMAT techniques in treatment planning for postoperative gastric cancer. In this article, we report our planning analysis for locally advanced gastric cancer after surgery, comparing the dosimetric parameters derived from 3D-CRT, IMRT, and VMAT plans.
Patients underwent computed tomography (CT)-based simulation in the supine position (Siemens, Somatom Plus4) with 3-mm CT slices. A custom immobilization device was used to minimize setup variability. All of the CT images of the patients were transferred to and registered in the treatment planning system (TPS). Targets and normal tissues definitions in this study were in accordance with the Radiation Therapy Oncology Group 50 and 62 reports.14,15 The clinical tumor volume typically included the original tumor volume, operative bed (as defined by the operative note, pathologic findings, surgical clips, and discussion with the surgeon), and the draining lymphatics at risk, as was described in the INT 0116 study.3 For the planning target volume (PTV), the 10-mm margin was added isotropically to the clinical tumor volume. The organs at risk (OARs) included spinal cord, heart, kidneys, liver, heart, and intestine. A single physician was assigned for the entire contouring task to avoid any inconstancy among various physicians. All generated plans for each patient consisted of 50.4 Gy to be delivered to PTV in 28 fractions. The objective of planning was to ensure 95% volume of PTV receiving the prescribed dose and avoiding the volume receiving 115% of the prescribed dose. All plans were generated for the Elekta Synergy accelerator (Elekta Oncology Systems, Crawley, UK) with 6-MV photons. The dose-volume constraints for the OARs were set as follows: 60% volume of the liver less than 30 Gy and mean liver dose less than 20 Gy; 30% volume of each kidney less than 22 Gy or two-thirds of 1 kidney less than 18 Gy; 95% volume of the intestine less than 45 Gy and maximum dose to the intestine less than 54 Gy; maximum dose to the spinal cord less than 45 Gy; and 30% volume of the heart less than 40 Gy. Treatment planning and optimizing (1)
(2)
Methods and Materials This study was conducted between June 2011 and January 2012. In total, 12 patients with confirmed locally advanced gastric cancer who had undergone surgery were randomly selected for analysis. These patients were treated following the protocol as we reported previously (radiotherapy with regimen of oxaliplatin, 5-fluorouracil, and leucovorin).12 The patient characteristics were listed in Table 1. All patients were staged according to the 2010 American Joint Committee on Cancer staging system.13 Permission to conduct the study was granted by the Research Ethics Board of the University Health Network.
(3)
3D-CRT: These plans were generated using the 4 coplanar beams with 3D conformal dose distribution for the targets in our TPS. Typically, the beams included an anteroposterior-posteroanterior parallel pair and 2 wedged lateral fields. The adjustments of the beam angles, wedge angles, weight coefficient, and other parameters were applied to avoid the OARs, especially the spinal cord and kidneys (Fig. 1A). IMRT: The IMRT plans were optimized with a Direct Machine Parameter Optimization algorithm in our TPS (Pinnacle3 9.0 version, Philips Medical System, Madison, WI), as described previously.16 For each plan, an average of 40 segments were used based on 7 coplanar beams (whose angles were 2041, 2561, 3081, 01, 521, 1041, and 1561, respectively) with the angles dependent on the tumor location (Fig. 1B). In the plan generation, the maximum iterations in the plan optimization were 40, and the maximum number of all segments in one plan was restricted to 100. There was no limitation to the minimum monitor units per segment. The OAR dose constraints and the priority weights were set in the plan optimization as the following: for the left kidney, the V30 o 10% (priority weight 30%) and the V20 o 23% (priority weight 30%); for the right kidney, the V30 o 5% (priority weight 30%) and the V20 o 18% (priority weight 30%); for the liver, the V30 o 15% (priority weight 15%) and the V20 o50% (priority weight 25%); for the intestine, the V40 o 17% (priority weight 30%) and the V50 o 8% (priority weight 10%); for the spinal cord, the maximum dose o 39 Gy (priority weight 15%); and for the heart, the V40 o 15% (priority weight 5%). Single-arc VMAT (sVMAT): The VMAT plans were optimized with the SmartArc planning algorithm in the Pinnacle system. The plan was constrained to use one single 3601 arc consisting of 90 control points. The arc was represented by 89 beams with each separated by 41 (Fig. 1C), which started and ended at 1801. The accelerator used an automatic dose rate selection, which ensured that the maximal possible dose rate was chosen for each individual segment of the arc. We applied the same OAR dose constraints and the priority weights as we set in the IMRT planning.
Fig. 1. Representative beam arrangements (A: 3D-CRT plan, B: IMRT plan, and C: VMAT plan). (Color version of figure is available online.)
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Fig. 2. Transverse sections of the representative plans of 1 patient with the irradiation isodose curves (A: 3D-CRT plan, B: IMRT plan, and C: VMAT plan). The green, blue, purple, and red lines represent the dose curves of the 80%, 90%, 95%, and 110% of the prescription dose (50.4 Gy), respectively. (Color version of figure is available online.)
Evaluation of the DVH-based parameters The homogeneous index for PTV was calculated as we applied previously.16 The homogeneous index was defined as the minimum dose in 5% of the PTV (D5)/ maximum dose in 95% of the PTV (D95). As the values of D5 and D95 approach each other, the steeper the target's curve in DVHs. The conformity index (CI) was defined as PTVRI/PTV*PTVRI/VRI, where the PTVRI indicated the PTV volume covered by the reference isodose, PTV indicated the PTV volume, and the VRI indicated the volume of the reference isodose.17 The CI ranges from 0 to 1, where 1 is the ideal value. The evaluated parameters were collected from the DVH of these generated plans and compared, including the maximum, mean, and minimum dose of the PTV, V20/30 (the percentage volumes that received 20 Gy and 30 Gy), and average dose (mean kidney dose [MKD] and mean liver dose) of each kidney and liver, V40/50 (the percentage volumes that received 40 Gy and 50 Gy) of the intestine and heart, Dmax and D5 (the maximum dose and the dose that 5% volume of the spinal cord received) of the spinal cord.
Statistical analysis The collected data were analyzed applying mean ⫾ standard deviation with SPSS software (version 13.0, Chicago, IL). Based on the Wilcoxon signed rank test, a p value less than 0.05 was considered to be statistically significant.
Results There were 36 generated plans evaluated with current treatment protocols with different planning methodologies. The transverse sections of the representative plans with irradiation dose curves for 1 patient are shown in Fig. 2. The comparisons of the parameters of the PTV are shown in Table 2. Although no significant difference was observed between the minimum dose of the PTV in this study, the mean dose of the PTV in the sVMAT plans was significantly higher than in the 3DCRT and IMRT plans (p o 0.05). In addition, the maximum dose of
the PTV using the sVMAT technique was much higher than that using the 3D-CRT technique (p ¼ 0.005). Based on evaluation of the PTV, the IMRT plans did not show an advantage compared with the 3D-CRT plans (p 4 0.05). Also, the IMRT and sVMAT plans achieved the superior CI (0.822 ⫾ 0.034 and 0.820 ⫾ 0.031) than the 3D-CRT plan (0.690 ⫾ 0.038, p o 0.001). The comparisons of the parameters of the OARs in the present study are also shown in Table 3. Compared with the 3D-CRT technique, the IMRT and sVMAT techniques improved the left kidney dose sparing in V20 (24.0 ⫾ 6.5 and 22.9 ⫾ 6.6), V30 (10.5 ⫾ 5.3 and 10.1 ⫾ 5.2), and MKD (14.6 ⫾ 2.3 and 14.8 ⫾ 2.4) (p o 0.01). Similarly, the V20 and V30 of the liver in the IMRT (54.4 ⫾ 7.1 and 23.7 ⫾ 4.2) and sVMAT plans (46.7 ⫾ 5.8 and 23.3 ⫾ 3.6) were significantly lower than in the 3D-CRT plans (p o 0.05). For the spinal cord, the 3D-CRT technique reduced the Dmax and D5 in the present study, compared with the IMRT and sVMAT techniques with statistical significance (p o 0.01). The IMRT and sVMAT plans did not show advantages in dose sparing of other evaluated OARs (V20, V30, and MKD to the right kidney; V40, and D50 to the intestine and heart). These differences between the 3D-CRT, IMRT, and sVMAT plans were not statistically significant (p 4 0.05). In this dosimetric study, the sVMAT technique only significantly improved the V20 (46.7 ⫾ 5.8) of the liver compared with the IMRT plans (54.4 ⫾ 7.1, p ¼ 0.008). Also, it failed to show a better target dose distribution and other normal tissue dose sparing than the IMRT technique (Fig. 3).
Discussion The dosimetric advantages of conformal radiotherapy have been stated, compared with the 2-dimensional techniques.
Table 2 Comparisons of the DVH-based parameters of the PTV in present study (n ¼ 12)
Dmin‡ (Gy) Dmean‡ (Gy) Dmax‡ (Gy) CI§ HI║
3D-CRT
IMRT
Mean ⫾ SD
Mean ⫾ SD
38.84 52.68 56.43 0.690 1.085
⫾ ⫾ ⫾ ⫾ ⫾
3.60 0.58 1.33 0.038 0.019
40.33 52.74 57.24 0.822 1.084
sVMAT
⫾ ⫾ ⫾ ⫾ ⫾
2.19 0.30 0.66 0.034 0.010
SD ¼ standard deviation; HI ¼ homogeneous index. n
Compared with the parameters of 3D-CRT plans. Compared with the parameters of IMRT plans. ‡ The minimum, maximum, and mean irradiation dose of the PTV, respectively. § Conformity index, calculated with the formula as described previously.17 ║ Homogeneous index, calculated with the formula: “HI ¼ D5/D95.” †
p Valuen
Mean ⫾ SD
0.234 0.753 0.072 o0.001 0.873
40.82 53.22 57.86 0.820 1.088
⫾ ⫾ ⫾ ⫾ ⫾
1.95 0.43 0.88 0.031 0.014
p Valuen
p Value†
0.108 0.017 0.005 o0.001 0.772
0.569 0.004 0.064 0.882 0.645
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Table 3 Comparisons of the DVH-based parameters of the OARsn in the present study (n ¼ 12)
Right kidney V20§ (%) V30§ (%) MKD║ (Gy) Left kidney V20 (%) V30 (%) MKD (Gy) Liver V20 (%) V30 (%) MLD║ (Gy) Spinal cord Dmax¶ (Gy) D5# (Gy) Intestine V40§ (%) V50§ (%) Heart V40§ (%) V50§ (%)
3D-CRT
IMRT
Mean ⫾ SD
Mean ⫾ SD
sVMAT p Value†
Mean ⫾ SD
p Value†
p Value‡
16.0 ⫾ 10.0 6.1 ⫾ 4.9 9.4 ⫾ 3.3
18.6 ⫾ 7.3 3.9 ⫾ 2.5 11.7 ⫾ 3.3
0.475 0.168 0.102
17.6 ⫾ 9.8 3.2 ⫾ 2.7 12.0 ⫾ 3.9
0.696 0.089 0.092
0.780 0.517 0.841
51.0 ⫾ 12.7 25.8 ⫾ 13.8 20.7 ⫾ 4.6
24.0 ⫾ 6.5 10.5 ⫾ 5.3 14.6 ⫾ 2.3
o0.001 0.002 o0.001
22.9 ⫾ 6.6 10.1 ⫾ 5.2 14.8 ⫾ 2.4
o0.001 0.001 o0.001
0.685 0.854 0.837
65.6 ⫾ 6.6 29.1 ⫾ 7.6 24.6 ⫾ 2.5
54.4 ⫾ 7.1 23.7 ⫾ 4.2 23.4 ⫾ 1.6
o0.001 0.042 0.175
46.7 ⫾ 5.8 23.3 ⫾ 3.6 22.9 ⫾ 1.3
o0.001 0.026 0.079
0.008 0.805 0.252
36.4 ⫾ 2.9 30.6 ⫾ 2.5
39.5 ⫾ 1.4 36.2 ⫾ 1.8
0.003 o0.001
40.6 ⫾ 1.5 37.3 ⫾ 2.2
o0.001 o0.001
0.077 0.194
41.9 ⫾ 11.4 29.5 ⫾ 10.4
39.0 ⫾ 13.1 22.3 ⫾ 11.1
0.569 0.115
38.5 ⫾ 12.8 21.4 ⫾ 10.7
0.499 0.073
0.926 0.842
11.42 ⫾ 8.91 5.80 ⫾ 5.42
10.79 ⫾ 7.99 4.34 ⫾ 4.02
0.857 0.462
11.82 ⫾ 8.29 5.13 ⫾ 4.32
0.914 0.741
0.760 0.647
MLD ¼ mean liver dose; SD ¼ standard deviation. n
Organs at risk. Compared with the parameters of 3D-CRT plans. ‡ Compared with the parameters of IMRT plans. § The volume of the lung that received the 20, 30, 40, and 50 Gy irradiation dose, respectively. ║ The mean irradiation dose that the kidneys and liver received, respectively. ¶ The maximum irradiation dose that the spinal cord received. # The irradiation dose that the 5% volume of the spinal cord received. †
However, since the implementation of the IMRT, no clear conclusion regarding its place in adjuvant treatment of gastric cancer has been reached.4–7 At present, as the VMAT technique has been applied in practice, the issue of whether it could compromise the plan quality compared with 3D-CRT and IMRT techniques has been discussed. For the first time, our study evaluated the dosimetric
differences between 3D-CRT, IMRT, and VMAT plans in the treatment of postoperation gastric cancer. Considering the OARs in the adjuvant radiation for the gastric cancer, the kidney is one of the most important organs in such dosimetric studies. But even in the same regimen of a prescription dose of 45 Gy in 25 fractions, different results were reported by
Fig. 3. Representative dose-volume histogram of the OARs. The thin, medium, and dashed lines indicate the 3D-CRT, IMRT, and VMAT plans, respectively. (Color version of figure is available online.)
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researchers in comparisons between 3D-CRT and IMRT techniques.5,7,18,19 Ringash et al.18 reported that IMRT improved all sparing of critical organs including the kidneys in their evaluation of 20 patients. Minn et al.19 from Stanford University also found that IMRT might provide sparing to the kidneys and possibly renal function. In line with these studies, our dosimetric data indicated that IMRT and VMAT successfully improved the V20/30 and mean dose of the left kidney but not the right one, compared with the 3D-CRT plans (all p o 0.01). However, in a 14-patient study, Alani et al. stated that IMRT technique conferred only a marginal benefit in the adjuvant radiation for gastric cancer, and only should be used in a small group of patients with risk factors for kidney disease.7 And Chung et al. reported that IMRT improved PTV dose coverage and liver doses but not kidney doses.5 In practice, 2 clinical investigations observed that serum creatinine level after chemoradiotherapy were significantly better in the IMRT group compared with the 3D-CRT group.19,20 Based on these studies reported recently, IMRT still has the potential for dose sparing of the kidney (especially the left kidney) in adjuvant radiation for gastric cancer in our mind. The liver is another key organ that should be paid more attention in such treatment for gastric cancer, as chemotherapy often has an effect on hepatic function. Results reported by Chung et al.,7 Ringash et al.,18 and Minn et al.19 indicated that IMRT might improve dose sparing of the liver. In the present study, the V20/30 of the liver was significantly better in IMRT and VMAT plans compared with the 3D-CRT plans (all p o 0.01). Unfortunately, no clinical evidence has been observed that the dosimetric advantages of the modern techniques could transfer to the survival benefits of the patients in practice yet. In the study by Dahele et al.,21 to compare the dosimetric differences between the IMRT and tomotherapy,4 they applied the same contouring protocol but different prescription doses (45 Gy/ 25 fractions) and OAR constraints as we did in the present study. In their planning, a jaw width of 2.5 cm, pitch of 0.3, modulation factor of 2 to 3, and normal dose-grid resolution ( 2 to 4 mm) were used. They reported that the conventional IMRT can achieve comparable PTV coverage and liver/kidney dose sparing to tomotherapy, but at the expense of PTV dose heterogeneity, which was in line with our results. By contrast, the irradiation doses of the spinal cord (Dmax and D5) in the 3D-CRT plans were significantly better than doses in the IMRT and VMAT plans (p o 0.01). However, the Dmax in the IMRT (39.5 ⫾ 1.4 Gy) and VMAT (40.6 ⫾ 1.5 Gy) plans were all less than 42 Gy, which were the constraints of the spinal cord in plan generation in the present study. The spinal cord is a “series-type” organ. And the irradiation tolerance of the spinal cord, the TD5/5, is possibly in the range of 50 Gy for single daily fractions of 1.8 to 2.0 Gy.22 However, the liver and kidney are the “parallel-type” organs, and the constraints of them should be the “dose-volume” restriction. Thus, in our plan generation, we gave more priority to the kidney and liver constraints and less priority to the spinal cord reduction (but still within the 42 Gy) in an attempt to improve the dose sparing of the liver/kidney as much as possible. Although the differences of the DVH-based parameters of the cord are significant among these 3 techniques, we considered that they had few values in the evaluation of the treatment plans and could be ignored in practice. If we put the different weight coefficients to the spinal cord, liver, and kidney in the plan optimization, the results might be entirely changed. In our study, we did not find significant differences in dose sparing of other OARs (right kidney, intestine, and heart) between the 3D-CRT, IMRT, and plans in adjuvant radiation for gastric cancers. Some of our results indicated that the IMRT and VMAT techniques might improve the dose sparing of specific OARs
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compared with the 3D-CRT technique in the present study. Although we did not observe the dosimetric advantages of the VMAT technique over IMRT, it only improved the V20 of the liver with a statistical significance of p o 0.01. Although the treatment time would be less than the time of the IMRT technique in plan delivering, VMAT did not show a superior target dose coverage and better dose sparing of the normal tissues in adjuvant treatment for gastric cancer as it did in other cancer types.4,23–25 So far, several studies had investigated the dosimetric differences between the single- and dual (or mor)-arc VMAT techniques. Guckenberger et al.25 reported that the dual- or triple-arc VMAT improved the target coverage and dose homogeneity compared with single-arc VMAT, although it increased delivery times, the MUs, and the spread of low doses. In addition, data from Verbakel et al.26 indicated that in head-and-neck cancer, the dual-arc VMAT plans provided at least similar sparing of OARs and better target dose homogeneity than single-arc VMAT or IMRT. From this point of view, multiarc VMAT technique might achieve better results than the single-arc VMAT did. In the present study, considering the simpleness of the PTV shape, we did not evaluate the dual- or triple-arc VMAT techniques as the adjuvant treatment for gastric cancer. Another issue should be pointed out. The CI is a complementary method that can evaluate a treatment plan or compare several treatment plans for the same patient. Since last decade, there were a few reports focused on this topic. Totally, 3 formulas had been applied in the evaluation of the target dose coverage.17,27–29 According to the review of the Feuvret et al.,30 the formula that was proposed by van't Riet et al. could compensate for the defects of the other 2 formulas. So, in our analysis, we chose this one as the evaluation tool for the target dose conformity. The limitation of this study should also be addressed. This work was purely a dosimetric planning study and it consequently would be affected by the original location of the tumor, the definition of the target, the target delineation by a radiation oncologist, the TPS installed in different centers, and other factors, such as the experience of the physicists. In addition, all such dosimetric differences need to be verified in clinical investigations.
Conclusions The IMRT and sVMAT plans achieved similar dose distribution to the target, but superior to the 3D-CRT plans, in adjuvant radiotherapy for gastric cancer. The sVMAT technique improved the dose sparings of the left kidney and liver, compared with the 3D-CRT technique, but showed few dosimetric advantages over the IMRT technique. Studies are warranted to evaluate the clinical benefits of the VMAT treatment for patients with gastric cancer after surgery in the future.
References 1. Gunderson, L.L.; Sosin, H. Adenocarcinoma of the stomach: areas of failure in a re-operation series (second or symptomatic look) clinicopathologic correlation and implications for adjuvant therapy. Int. J. Radiat. Oncol. Biol. Phys. 11:1–11; 1982. 2. Landry, J.; Tepper, J.E.; Wood, W.C.; et al. Patterns of failure following curative resection of gastric carcinoma. Int. J. Radiat. Oncol. Biol. Phys. 19:1357–62; 1990. 3. Macdonald, J.S.; Smalley, S.R.; Benedetti, J.; et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N. Engl. J. Med. 345:725–30; 2001. 4. Max, D.; Matthew, S.; Brenda, S.; et al. Adjuvant radiotherapy for gastric cancer: a dosimetric comparison of 3-dimensional conformal radiotherapy, tomotherapys and conventional intensity modulated radiotherapy treatment plans. Med. Dosim. 35:115–21; 2010. 5. Chung, H.T.; Lee, B.; Park, E.; et al. Can all centers plan intensity-modulated radiotherapy (IMRT) effectively? An external audit of dosimetric comparisons between three-dimensional conformal radiotherapy and IMRT for adjuvant
6
6.
7.
8.
9.
10. 11. 12.
13. 14. 15. 16.
17.
18.
X. Wang et al. / Medical Dosimetry ] (2013) ]]]–]]] chemoradiation for gastric cancer Int. J. Radiat. Oncol. Biol. Phys. 71:1167–74; 2008. Milano, M.T.; Garofalo, M.C.; Chmura, S.J.; et al. Intensity-modulated radiation therapy in the treatment of gastric cancer: early clinical outcome and dosimetric comparison with conventional techniques. Br. J. Radiol. 79:497–503; 2006. Alani, S.; Soyfer, V.; Strauss, N.; et al. Limited advantages of intensity-modulated radiotherapy over 3D conformal radiation therapy in the adjuvant management of gastric cancer. Int. J. Radiat. Oncol. Biol. Phys. 74:562–6; 2009. Scorsetti, M.; Navarria, P.; Mancosu, P.; et al. Large volume unresectable locally advanced non-small cell lung cancer: acute toxicity and initial outcome results with rapid arc. Radiat. Oncol. 5:94; 2010. McGrath, S.D.; Mathuszak, M.M.; Yan, D.; et al. Volumetric modulated arc therapy for delivery of hypofractionated stereotactic lung radiotherapy: a dosimetric and treatment efficiency analysis. Radiother. Oncol. 95:153–7; 2010. Pesce, G.A.; Clivio, A.; Cozzi, L.; et al. Early clinical experience of radiotherapy of prostate cancer with volumetric modulated arc therapy. Radiat. Oncol. 5:54; 2010. Stieler, F.; Wolff, D.; Lohr, F.; et al. A fast radiotherapy paradigm for anal cancer with volumetric modulated arc therapy (VMAT). Radiat. Oncol. 4:48; 2009. Wang, X.; Wang, Y.S.; Qiu, M.; et al. Postoperative chemoradiotherapy in gastric cancer: a phase I study of radiotherapy with dose escalation of oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX regimen). Med. Oncol. 28:S274–9; 2011. Edge, S.B.; Byrd, D.R.; Compton, C.C.; et al. AJCC cancer staging manual (6th ed). New York: Springer; 2010. International Commission on Radiation Units and Measurements. Prescribing, Recording, and Reporting Photon Beam Therapy. Bethesda, MD, ICRU, 1993. Wambersie, A.; Landberg, T. ICRU Report 62: Prescribing, Recording and Reporting Photon Beam Therapy (Supplement to ICRU Report 50); 1999. Gong, Y.L.; Wang, S.C.; Zhou, L.; et al. Dosimetric comparison using different multileaf collimeters in intensity-modulated radiotherapy for upper thoracic esophageal cancer. Radiat. Oncol. 5:65; 2010. van't Riet, A.; Mak, A.C.; Moerland, M.A.; et al. A conformation number to quantify the degree of conformality in brachytherapy and external beam irradiation: application to the prostate. Int. J. Radiat. Oncol. Biol. Phys. 37:731–6; 1997. Ringash, J.; Perkins, G.; Brierley, J.; et al. IMRT for adjuvant radiation in gastric cancer: a preferred plan? Int. J. Radiat. Oncol. Biol. Phys. 63:732–8; 2005.
19. Minn, A.Y.; Hsu, A.; La, T.; et al. Comparison of intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy as adjuvant therapy for gastric cancer. Cancer 116:3943–52; 2010. 20. Boda-Heggemann, J.; Hofheinz, R.D.; Weiss, C.; et al. Combines adjuvant radiochemotherapy with IMRT/XELOX improves outcome with low renal toxicity in gastric cancer. Int. J. Radiat. Oncol. Biol. Phys. 75:1187–95; 2009. 21. Dahele, M.; Skinner, M.; Schultz, B.; Cardoso, M.; Bell, C.; Ung, Y.C. Adjuvant radiotherapy for gastric cancer: a dosimetric comparison of 3-dimensional conformal radiotherapy, tomotherapy® and conventional intensity modulated radiotherapy treatment plans. Med. Dosim. 35:115–21; 2010. 22. Marcus Jr R.B.; Million, R.R. The incidence of myelitis after irradiation of the cervical spinal cord. Int. J. Radiat. Oncol. Biol. Phys. 19:3–8; 1990. 23. Holt, A.; van Vroegindeweij, C.; Mans, A.; et al. Volumetric-modulated arc therapy for stereotactic dose radiotherapy of lung tumors: a comparison with intensity modulated radiotherapy techniques. Int. J. Radiat. Oncol. Biol. Phys. 81:1560–7; 2011. 24. Bertelsen, A.; Hansen, C.R.; Johansen, J.; et al. Single arc volumetric modulated arc therapy of head and neck cancer. Radiother. Oncol. 95:142–8; 2010. 25. Guckenberger, M.; Richter, A.; Krieger, T.; et al. Is a single arc sufficient in volumetric-modulated arc therapy (VMAT) for complex-shaped target volumes? Radiother. Oncol. 93:259–65; 2009. 26. Verbakel, W.F.; Cuijpers, J.P.; Hoffmans, D.; et al. Volumetric intensitymodulated arc therapy vs. conventional IMRT in head-and-neck cancer: a comparative planning and dosimetric study. Int. J. Radiat. Oncol. Biol. Phys. 74:252–9; 2009. 27. Shaw, E.; Scott, C.; Souhami, L.; et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int. J. Radiat. Oncol. Biol. Phys. 47:291–8; 2000. 28. Huchet, A.; Caudry, M.; Belkacemi, Y.; et al. Volume-effect and radiotherapy part two: volume-effect and normal tissue. Cancer Radiother. 7:353–62; 2003. 29. Lefkopoulos, D.; Dejean, C.; El-Balma, H.; et al. Determination of dose-volumes parameters to characterise the conformity of stereotactic treatment plans. In: XIIIth Intern. Conf. on: Computers in Radiation Therapy, [XIIIth ICCR, Heidelberg, Germany]. 356–8; 2000. 30. Feuvret, L.; Noel, G.; Mazeron, J.J.; Bey, P. Conformity index: a review. Int. J. Radiat. Oncol. Biol. Phys. 64:333–42; 2006.
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Single-arc volumetric-modulated arc therapy (sVMAT) as adjuvant treatment for gastric cancer: Dosimetric comparisons with three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT) Xin Wang, M.D., Ph.D.,n,1 Guangjun Li, M.S.,† Yingjie Zhang, M.S.,† Sen Bai, Ph.D.,† Feng Xu, M.D.,n Yuquan Wei, M.D., Ph.D.,‡ and Youling Gong, M.D., Ph.D.‡ *Department of Abdominal Oncology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, P.R. China; †Radiation Physics Center, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, P.R. China; and ‡Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, P.R. China
A R T I C L E I N F O
A B S T R A C T
Article history: Received 6 June 2012 Accepted 26 April 2013
To compare the dosimetric differences between the single-arc volumetric-modulated arc therapy (sVMAT), 3-dimensional conformal radiotherapy (3D-CRT), and intensity-modulated radiotherapy (IMRT) techniques in treatment planning for gastric cancer as adjuvant radiotherapy. Twelve patients were retrospectively analyzed. In each patient's case, the parameters were compared based on the dosevolume histogram (DVH) of the sVMAT, 3D-CRT, and IMRT plans, respectively. Three techniques showed similar target dose coverage. The maximum and mean doses of the target were significantly higher in the sVMAT plans than that in 3D-CRT plans and in the 3D-CRT/IMRT plans, respectively, but these differences were clinically acceptable. The IMRT and sVMAT plans successfully achieved better target dose conformity, reduced the V20/30, and mean dose of the left kidney, as well as the V20/30 of the liver, compared with the 3D-CRT plans. And the sVMAT technique reduced the V20 of the liver much significantly. Although the maximum dose of the spinal cord were much higher in the IMRT and sVMAT plans, respectively (mean 36.4 vs 39.5 and 40.6 Gy), these data were still under the constraints. Not much difference was found in the analysis of the parameters of the right kidney, intestine, and heart. The IMRT and sVMAT plans achieved similar dose distribution to the target, but superior to the 3D-CRT plans, in adjuvant radiotherapy for gastric cancer. The sVMAT technique improved the dose sparings of the left kidney and liver, compared with the 3D-CRT technique, but showed few dosimetric advantages over the IMRT technique. Studies are warranted to evaluate the clinical benefits of the VMAT treatment for patients with gastric cancer after surgery in the future. & 2013 American Association of Medical Dosimetrists.
Keywords: Gastric cancer Volumetric-modulated arc therapy Three-dimensional conformal radiotherapy Intensity-modulated radiotherapy Dosimetric comparison
Introduction Gastric cancer occurs with high incidence rate in West China. Although there are many protocols in managing of this type of disease, surgery remains as the key strategy of the treatment for the locally advanced gastric cancer. After operation, the locoregional relapse rate was nearly 30% to 50%, and almost half of these relapses were the only sites of the failures observed in clinical
Reprint requests to: Youling Gong, Department of Thoracic Oncology and State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, P.R. China. Tel.: þ86 2885 423 581; fax: þ86 2885 424 619. E-mail: [email protected] 1 Dr. Xin Wang and Guangjun Li contributed equally to this work.
practice.1,2 As the results of the Gastric Surgical Adjuvant Trial Intergroup 0116 (INT 0116) were published, chemoradiotherapy was established as the standard adjuvant treatment for locoadvanced gastric cancer after surgery.3 In this landmark trial, adjuvant chemoradiotherapy improved the 3-year median survival to 36 months compared with 27 months in the surgery-alone group in T3/4 or N-positive patients with high-risk, resected gastric cancer. INT 0116 radiation therapy approach has involved 2-dimensional treatment planning, mostly with a standard anteroposteriorposteroanterior field arrangement. The consequences were obvious, giving rise to the side-effects that necessitated termination of the therapy in nearly 17% of patients.3 With the development of conformal radiotherapy, 3-dimensional conformal radiotherapy (3D-CRT) showed a superior dose distribution and normal tissue sparing, and became the routine application in radiotherapy treatment planning. As the
0958-3947/$ – see front matter Copyright Ó 2013 American Association of Medical Dosimetrists http://dx.doi.org/10.1016/j.meddos.2013.04.007
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Target delineation and dose prescription
Table 1 Basic and clinical characteristics of the studied patients (n ¼ 12) Age (y) Median Range Sex Male Female Disease stage II IIIA IIIB IV (M0) Tumor location Upper third Middle third Lower third Extent of node dissection D1 D2
57 43 to 70 7 5 2 3 5 2 4 4 4 2 10
implementation of the intensity-modulated radiotherapy (IMRT), the issue of whether the IMRT technique was better than the 3D-CRT technique as adjuvant treatment for gastric cancer has been discussed, and the conclusions have been considered as controversial.4–7 Volumetric-modulated arc therapy (VMAT), a rotational form of IMRT, has been introduced into clinical practice with other treatment methodologies recently, including lung cancers,8,9 prostate cancer,10 and anal cancer.11 Based on a number of studies, it has been pointed out that the VMAT technique might reduce the treatment time without compromising plan quality compared with IMRT in radiotherapy planning for different cancer types. In adjuvant treatment planning for gastric cancer, only one study focused on the dosimetric differences between IMRT and arc radiotherapy (tomotherapy), which indicated that tomotherapy was similar to the IMRT technique.4 Until now, no study has been published comparing the 3D-CRT, IMRT, and VMAT techniques in treatment planning for postoperative gastric cancer. In this article, we report our planning analysis for locally advanced gastric cancer after surgery, comparing the dosimetric parameters derived from 3D-CRT, IMRT, and VMAT plans.
Patients underwent computed tomography (CT)-based simulation in the supine position (Siemens, Somatom Plus4) with 3-mm CT slices. A custom immobilization device was used to minimize setup variability. All of the CT images of the patients were transferred to and registered in the treatment planning system (TPS). Targets and normal tissues definitions in this study were in accordance with the Radiation Therapy Oncology Group 50 and 62 reports.14,15 The clinical tumor volume typically included the original tumor volume, operative bed (as defined by the operative note, pathologic findings, surgical clips, and discussion with the surgeon), and the draining lymphatics at risk, as was described in the INT 0116 study.3 For the planning target volume (PTV), the 10-mm margin was added isotropically to the clinical tumor volume. The organs at risk (OARs) included spinal cord, heart, kidneys, liver, heart, and intestine. A single physician was assigned for the entire contouring task to avoid any inconstancy among various physicians. All generated plans for each patient consisted of 50.4 Gy to be delivered to PTV in 28 fractions. The objective of planning was to ensure 95% volume of PTV receiving the prescribed dose and avoiding the volume receiving 115% of the prescribed dose. All plans were generated for the Elekta Synergy accelerator (Elekta Oncology Systems, Crawley, UK) with 6-MV photons. The dose-volume constraints for the OARs were set as follows: 60% volume of the liver less than 30 Gy and mean liver dose less than 20 Gy; 30% volume of each kidney less than 22 Gy or two-thirds of 1 kidney less than 18 Gy; 95% volume of the intestine less than 45 Gy and maximum dose to the intestine less than 54 Gy; maximum dose to the spinal cord less than 45 Gy; and 30% volume of the heart less than 40 Gy. Treatment planning and optimizing (1)
(2)
Methods and Materials This study was conducted between June 2011 and January 2012. In total, 12 patients with confirmed locally advanced gastric cancer who had undergone surgery were randomly selected for analysis. These patients were treated following the protocol as we reported previously (radiotherapy with regimen of oxaliplatin, 5-fluorouracil, and leucovorin).12 The patient characteristics were listed in Table 1. All patients were staged according to the 2010 American Joint Committee on Cancer staging system.13 Permission to conduct the study was granted by the Research Ethics Board of the University Health Network.
(3)
3D-CRT: These plans were generated using the 4 coplanar beams with 3D conformal dose distribution for the targets in our TPS. Typically, the beams included an anteroposterior-posteroanterior parallel pair and 2 wedged lateral fields. The adjustments of the beam angles, wedge angles, weight coefficient, and other parameters were applied to avoid the OARs, especially the spinal cord and kidneys (Fig. 1A). IMRT: The IMRT plans were optimized with a Direct Machine Parameter Optimization algorithm in our TPS (Pinnacle3 9.0 version, Philips Medical System, Madison, WI), as described previously.16 For each plan, an average of 40 segments were used based on 7 coplanar beams (whose angles were 2041, 2561, 3081, 01, 521, 1041, and 1561, respectively) with the angles dependent on the tumor location (Fig. 1B). In the plan generation, the maximum iterations in the plan optimization were 40, and the maximum number of all segments in one plan was restricted to 100. There was no limitation to the minimum monitor units per segment. The OAR dose constraints and the priority weights were set in the plan optimization as the following: for the left kidney, the V30 o 10% (priority weight 30%) and the V20 o 23% (priority weight 30%); for the right kidney, the V30 o 5% (priority weight 30%) and the V20 o 18% (priority weight 30%); for the liver, the V30 o 15% (priority weight 15%) and the V20 o50% (priority weight 25%); for the intestine, the V40 o 17% (priority weight 30%) and the V50 o 8% (priority weight 10%); for the spinal cord, the maximum dose o 39 Gy (priority weight 15%); and for the heart, the V40 o 15% (priority weight 5%). Single-arc VMAT (sVMAT): The VMAT plans were optimized with the SmartArc planning algorithm in the Pinnacle system. The plan was constrained to use one single 3601 arc consisting of 90 control points. The arc was represented by 89 beams with each separated by 41 (Fig. 1C), which started and ended at 1801. The accelerator used an automatic dose rate selection, which ensured that the maximal possible dose rate was chosen for each individual segment of the arc. We applied the same OAR dose constraints and the priority weights as we set in the IMRT planning.
Fig. 1. Representative beam arrangements (A: 3D-CRT plan, B: IMRT plan, and C: VMAT plan). (Color version of figure is available online.)
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Fig. 2. Transverse sections of the representative plans of 1 patient with the irradiation isodose curves (A: 3D-CRT plan, B: IMRT plan, and C: VMAT plan). The green, blue, purple, and red lines represent the dose curves of the 80%, 90%, 95%, and 110% of the prescription dose (50.4 Gy), respectively. (Color version of figure is available online.)
Evaluation of the DVH-based parameters The homogeneous index for PTV was calculated as we applied previously.16 The homogeneous index was defined as the minimum dose in 5% of the PTV (D5)/ maximum dose in 95% of the PTV (D95). As the values of D5 and D95 approach each other, the steeper the target's curve in DVHs. The conformity index (CI) was defined as PTVRI/PTV*PTVRI/VRI, where the PTVRI indicated the PTV volume covered by the reference isodose, PTV indicated the PTV volume, and the VRI indicated the volume of the reference isodose.17 The CI ranges from 0 to 1, where 1 is the ideal value. The evaluated parameters were collected from the DVH of these generated plans and compared, including the maximum, mean, and minimum dose of the PTV, V20/30 (the percentage volumes that received 20 Gy and 30 Gy), and average dose (mean kidney dose [MKD] and mean liver dose) of each kidney and liver, V40/50 (the percentage volumes that received 40 Gy and 50 Gy) of the intestine and heart, Dmax and D5 (the maximum dose and the dose that 5% volume of the spinal cord received) of the spinal cord.
Statistical analysis The collected data were analyzed applying mean ⫾ standard deviation with SPSS software (version 13.0, Chicago, IL). Based on the Wilcoxon signed rank test, a p value less than 0.05 was considered to be statistically significant.
Results There were 36 generated plans evaluated with current treatment protocols with different planning methodologies. The transverse sections of the representative plans with irradiation dose curves for 1 patient are shown in Fig. 2. The comparisons of the parameters of the PTV are shown in Table 2. Although no significant difference was observed between the minimum dose of the PTV in this study, the mean dose of the PTV in the sVMAT plans was significantly higher than in the 3DCRT and IMRT plans (p o 0.05). In addition, the maximum dose of
the PTV using the sVMAT technique was much higher than that using the 3D-CRT technique (p ¼ 0.005). Based on evaluation of the PTV, the IMRT plans did not show an advantage compared with the 3D-CRT plans (p 4 0.05). Also, the IMRT and sVMAT plans achieved the superior CI (0.822 ⫾ 0.034 and 0.820 ⫾ 0.031) than the 3D-CRT plan (0.690 ⫾ 0.038, p o 0.001). The comparisons of the parameters of the OARs in the present study are also shown in Table 3. Compared with the 3D-CRT technique, the IMRT and sVMAT techniques improved the left kidney dose sparing in V20 (24.0 ⫾ 6.5 and 22.9 ⫾ 6.6), V30 (10.5 ⫾ 5.3 and 10.1 ⫾ 5.2), and MKD (14.6 ⫾ 2.3 and 14.8 ⫾ 2.4) (p o 0.01). Similarly, the V20 and V30 of the liver in the IMRT (54.4 ⫾ 7.1 and 23.7 ⫾ 4.2) and sVMAT plans (46.7 ⫾ 5.8 and 23.3 ⫾ 3.6) were significantly lower than in the 3D-CRT plans (p o 0.05). For the spinal cord, the 3D-CRT technique reduced the Dmax and D5 in the present study, compared with the IMRT and sVMAT techniques with statistical significance (p o 0.01). The IMRT and sVMAT plans did not show advantages in dose sparing of other evaluated OARs (V20, V30, and MKD to the right kidney; V40, and D50 to the intestine and heart). These differences between the 3D-CRT, IMRT, and sVMAT plans were not statistically significant (p 4 0.05). In this dosimetric study, the sVMAT technique only significantly improved the V20 (46.7 ⫾ 5.8) of the liver compared with the IMRT plans (54.4 ⫾ 7.1, p ¼ 0.008). Also, it failed to show a better target dose distribution and other normal tissue dose sparing than the IMRT technique (Fig. 3).
Discussion The dosimetric advantages of conformal radiotherapy have been stated, compared with the 2-dimensional techniques.
Table 2 Comparisons of the DVH-based parameters of the PTV in present study (n ¼ 12)
Dmin‡ (Gy) Dmean‡ (Gy) Dmax‡ (Gy) CI§ HI║
3D-CRT
IMRT
Mean ⫾ SD
Mean ⫾ SD
38.84 52.68 56.43 0.690 1.085
⫾ ⫾ ⫾ ⫾ ⫾
3.60 0.58 1.33 0.038 0.019
40.33 52.74 57.24 0.822 1.084
sVMAT
⫾ ⫾ ⫾ ⫾ ⫾
2.19 0.30 0.66 0.034 0.010
SD ¼ standard deviation; HI ¼ homogeneous index. n
Compared with the parameters of 3D-CRT plans. Compared with the parameters of IMRT plans. ‡ The minimum, maximum, and mean irradiation dose of the PTV, respectively. § Conformity index, calculated with the formula as described previously.17 ║ Homogeneous index, calculated with the formula: “HI ¼ D5/D95.” †
p Valuen
Mean ⫾ SD
0.234 0.753 0.072 o0.001 0.873
40.82 53.22 57.86 0.820 1.088
⫾ ⫾ ⫾ ⫾ ⫾
1.95 0.43 0.88 0.031 0.014
p Valuen
p Value†
0.108 0.017 0.005 o0.001 0.772
0.569 0.004 0.064 0.882 0.645
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Table 3 Comparisons of the DVH-based parameters of the OARsn in the present study (n ¼ 12)
Right kidney V20§ (%) V30§ (%) MKD║ (Gy) Left kidney V20 (%) V30 (%) MKD (Gy) Liver V20 (%) V30 (%) MLD║ (Gy) Spinal cord Dmax¶ (Gy) D5# (Gy) Intestine V40§ (%) V50§ (%) Heart V40§ (%) V50§ (%)
3D-CRT
IMRT
Mean ⫾ SD
Mean ⫾ SD
sVMAT p Value†
Mean ⫾ SD
p Value†
p Value‡
16.0 ⫾ 10.0 6.1 ⫾ 4.9 9.4 ⫾ 3.3
18.6 ⫾ 7.3 3.9 ⫾ 2.5 11.7 ⫾ 3.3
0.475 0.168 0.102
17.6 ⫾ 9.8 3.2 ⫾ 2.7 12.0 ⫾ 3.9
0.696 0.089 0.092
0.780 0.517 0.841
51.0 ⫾ 12.7 25.8 ⫾ 13.8 20.7 ⫾ 4.6
24.0 ⫾ 6.5 10.5 ⫾ 5.3 14.6 ⫾ 2.3
o0.001 0.002 o0.001
22.9 ⫾ 6.6 10.1 ⫾ 5.2 14.8 ⫾ 2.4
o0.001 0.001 o0.001
0.685 0.854 0.837
65.6 ⫾ 6.6 29.1 ⫾ 7.6 24.6 ⫾ 2.5
54.4 ⫾ 7.1 23.7 ⫾ 4.2 23.4 ⫾ 1.6
o0.001 0.042 0.175
46.7 ⫾ 5.8 23.3 ⫾ 3.6 22.9 ⫾ 1.3
o0.001 0.026 0.079
0.008 0.805 0.252
36.4 ⫾ 2.9 30.6 ⫾ 2.5
39.5 ⫾ 1.4 36.2 ⫾ 1.8
0.003 o0.001
40.6 ⫾ 1.5 37.3 ⫾ 2.2
o0.001 o0.001
0.077 0.194
41.9 ⫾ 11.4 29.5 ⫾ 10.4
39.0 ⫾ 13.1 22.3 ⫾ 11.1
0.569 0.115
38.5 ⫾ 12.8 21.4 ⫾ 10.7
0.499 0.073
0.926 0.842
11.42 ⫾ 8.91 5.80 ⫾ 5.42
10.79 ⫾ 7.99 4.34 ⫾ 4.02
0.857 0.462
11.82 ⫾ 8.29 5.13 ⫾ 4.32
0.914 0.741
0.760 0.647
MLD ¼ mean liver dose; SD ¼ standard deviation. n
Organs at risk. Compared with the parameters of 3D-CRT plans. ‡ Compared with the parameters of IMRT plans. § The volume of the lung that received the 20, 30, 40, and 50 Gy irradiation dose, respectively. ║ The mean irradiation dose that the kidneys and liver received, respectively. ¶ The maximum irradiation dose that the spinal cord received. # The irradiation dose that the 5% volume of the spinal cord received. †
However, since the implementation of the IMRT, no clear conclusion regarding its place in adjuvant treatment of gastric cancer has been reached.4–7 At present, as the VMAT technique has been applied in practice, the issue of whether it could compromise the plan quality compared with 3D-CRT and IMRT techniques has been discussed. For the first time, our study evaluated the dosimetric
differences between 3D-CRT, IMRT, and VMAT plans in the treatment of postoperation gastric cancer. Considering the OARs in the adjuvant radiation for the gastric cancer, the kidney is one of the most important organs in such dosimetric studies. But even in the same regimen of a prescription dose of 45 Gy in 25 fractions, different results were reported by
Fig. 3. Representative dose-volume histogram of the OARs. The thin, medium, and dashed lines indicate the 3D-CRT, IMRT, and VMAT plans, respectively. (Color version of figure is available online.)
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researchers in comparisons between 3D-CRT and IMRT techniques.5,7,18,19 Ringash et al.18 reported that IMRT improved all sparing of critical organs including the kidneys in their evaluation of 20 patients. Minn et al.19 from Stanford University also found that IMRT might provide sparing to the kidneys and possibly renal function. In line with these studies, our dosimetric data indicated that IMRT and VMAT successfully improved the V20/30 and mean dose of the left kidney but not the right one, compared with the 3D-CRT plans (all p o 0.01). However, in a 14-patient study, Alani et al. stated that IMRT technique conferred only a marginal benefit in the adjuvant radiation for gastric cancer, and only should be used in a small group of patients with risk factors for kidney disease.7 And Chung et al. reported that IMRT improved PTV dose coverage and liver doses but not kidney doses.5 In practice, 2 clinical investigations observed that serum creatinine level after chemoradiotherapy were significantly better in the IMRT group compared with the 3D-CRT group.19,20 Based on these studies reported recently, IMRT still has the potential for dose sparing of the kidney (especially the left kidney) in adjuvant radiation for gastric cancer in our mind. The liver is another key organ that should be paid more attention in such treatment for gastric cancer, as chemotherapy often has an effect on hepatic function. Results reported by Chung et al.,7 Ringash et al.,18 and Minn et al.19 indicated that IMRT might improve dose sparing of the liver. In the present study, the V20/30 of the liver was significantly better in IMRT and VMAT plans compared with the 3D-CRT plans (all p o 0.01). Unfortunately, no clinical evidence has been observed that the dosimetric advantages of the modern techniques could transfer to the survival benefits of the patients in practice yet. In the study by Dahele et al.,21 to compare the dosimetric differences between the IMRT and tomotherapy,4 they applied the same contouring protocol but different prescription doses (45 Gy/ 25 fractions) and OAR constraints as we did in the present study. In their planning, a jaw width of 2.5 cm, pitch of 0.3, modulation factor of 2 to 3, and normal dose-grid resolution ( 2 to 4 mm) were used. They reported that the conventional IMRT can achieve comparable PTV coverage and liver/kidney dose sparing to tomotherapy, but at the expense of PTV dose heterogeneity, which was in line with our results. By contrast, the irradiation doses of the spinal cord (Dmax and D5) in the 3D-CRT plans were significantly better than doses in the IMRT and VMAT plans (p o 0.01). However, the Dmax in the IMRT (39.5 ⫾ 1.4 Gy) and VMAT (40.6 ⫾ 1.5 Gy) plans were all less than 42 Gy, which were the constraints of the spinal cord in plan generation in the present study. The spinal cord is a “series-type” organ. And the irradiation tolerance of the spinal cord, the TD5/5, is possibly in the range of 50 Gy for single daily fractions of 1.8 to 2.0 Gy.22 However, the liver and kidney are the “parallel-type” organs, and the constraints of them should be the “dose-volume” restriction. Thus, in our plan generation, we gave more priority to the kidney and liver constraints and less priority to the spinal cord reduction (but still within the 42 Gy) in an attempt to improve the dose sparing of the liver/kidney as much as possible. Although the differences of the DVH-based parameters of the cord are significant among these 3 techniques, we considered that they had few values in the evaluation of the treatment plans and could be ignored in practice. If we put the different weight coefficients to the spinal cord, liver, and kidney in the plan optimization, the results might be entirely changed. In our study, we did not find significant differences in dose sparing of other OARs (right kidney, intestine, and heart) between the 3D-CRT, IMRT, and plans in adjuvant radiation for gastric cancers. Some of our results indicated that the IMRT and VMAT techniques might improve the dose sparing of specific OARs
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compared with the 3D-CRT technique in the present study. Although we did not observe the dosimetric advantages of the VMAT technique over IMRT, it only improved the V20 of the liver with a statistical significance of p o 0.01. Although the treatment time would be less than the time of the IMRT technique in plan delivering, VMAT did not show a superior target dose coverage and better dose sparing of the normal tissues in adjuvant treatment for gastric cancer as it did in other cancer types.4,23–25 So far, several studies had investigated the dosimetric differences between the single- and dual (or mor)-arc VMAT techniques. Guckenberger et al.25 reported that the dual- or triple-arc VMAT improved the target coverage and dose homogeneity compared with single-arc VMAT, although it increased delivery times, the MUs, and the spread of low doses. In addition, data from Verbakel et al.26 indicated that in head-and-neck cancer, the dual-arc VMAT plans provided at least similar sparing of OARs and better target dose homogeneity than single-arc VMAT or IMRT. From this point of view, multiarc VMAT technique might achieve better results than the single-arc VMAT did. In the present study, considering the simpleness of the PTV shape, we did not evaluate the dual- or triple-arc VMAT techniques as the adjuvant treatment for gastric cancer. Another issue should be pointed out. The CI is a complementary method that can evaluate a treatment plan or compare several treatment plans for the same patient. Since last decade, there were a few reports focused on this topic. Totally, 3 formulas had been applied in the evaluation of the target dose coverage.17,27–29 According to the review of the Feuvret et al.,30 the formula that was proposed by van't Riet et al. could compensate for the defects of the other 2 formulas. So, in our analysis, we chose this one as the evaluation tool for the target dose conformity. The limitation of this study should also be addressed. This work was purely a dosimetric planning study and it consequently would be affected by the original location of the tumor, the definition of the target, the target delineation by a radiation oncologist, the TPS installed in different centers, and other factors, such as the experience of the physicists. In addition, all such dosimetric differences need to be verified in clinical investigations.
Conclusions The IMRT and sVMAT plans achieved similar dose distribution to the target, but superior to the 3D-CRT plans, in adjuvant radiotherapy for gastric cancer. The sVMAT technique improved the dose sparings of the left kidney and liver, compared with the 3D-CRT technique, but showed few dosimetric advantages over the IMRT technique. Studies are warranted to evaluate the clinical benefits of the VMAT treatment for patients with gastric cancer after surgery in the future.
References 1. Gunderson, L.L.; Sosin, H. Adenocarcinoma of the stomach: areas of failure in a re-operation series (second or symptomatic look) clinicopathologic correlation and implications for adjuvant therapy. Int. J. Radiat. Oncol. Biol. Phys. 11:1–11; 1982. 2. Landry, J.; Tepper, J.E.; Wood, W.C.; et al. Patterns of failure following curative resection of gastric carcinoma. Int. J. Radiat. Oncol. Biol. Phys. 19:1357–62; 1990. 3. Macdonald, J.S.; Smalley, S.R.; Benedetti, J.; et al. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N. Engl. J. Med. 345:725–30; 2001. 4. Max, D.; Matthew, S.; Brenda, S.; et al. Adjuvant radiotherapy for gastric cancer: a dosimetric comparison of 3-dimensional conformal radiotherapy, tomotherapys and conventional intensity modulated radiotherapy treatment plans. Med. Dosim. 35:115–21; 2010. 5. Chung, H.T.; Lee, B.; Park, E.; et al. Can all centers plan intensity-modulated radiotherapy (IMRT) effectively? An external audit of dosimetric comparisons between three-dimensional conformal radiotherapy and IMRT for adjuvant
6
6.
7.
8.
9.
10. 11. 12.
13. 14. 15. 16.
17.
18.
X. Wang et al. / Medical Dosimetry ] (2013) ]]]–]]] chemoradiation for gastric cancer Int. J. Radiat. Oncol. Biol. Phys. 71:1167–74; 2008. Milano, M.T.; Garofalo, M.C.; Chmura, S.J.; et al. Intensity-modulated radiation therapy in the treatment of gastric cancer: early clinical outcome and dosimetric comparison with conventional techniques. Br. J. Radiol. 79:497–503; 2006. Alani, S.; Soyfer, V.; Strauss, N.; et al. Limited advantages of intensity-modulated radiotherapy over 3D conformal radiation therapy in the adjuvant management of gastric cancer. Int. J. Radiat. Oncol. Biol. Phys. 74:562–6; 2009. Scorsetti, M.; Navarria, P.; Mancosu, P.; et al. Large volume unresectable locally advanced non-small cell lung cancer: acute toxicity and initial outcome results with rapid arc. Radiat. Oncol. 5:94; 2010. McGrath, S.D.; Mathuszak, M.M.; Yan, D.; et al. Volumetric modulated arc therapy for delivery of hypofractionated stereotactic lung radiotherapy: a dosimetric and treatment efficiency analysis. Radiother. Oncol. 95:153–7; 2010. Pesce, G.A.; Clivio, A.; Cozzi, L.; et al. Early clinical experience of radiotherapy of prostate cancer with volumetric modulated arc therapy. Radiat. Oncol. 5:54; 2010. Stieler, F.; Wolff, D.; Lohr, F.; et al. A fast radiotherapy paradigm for anal cancer with volumetric modulated arc therapy (VMAT). Radiat. Oncol. 4:48; 2009. Wang, X.; Wang, Y.S.; Qiu, M.; et al. Postoperative chemoradiotherapy in gastric cancer: a phase I study of radiotherapy with dose escalation of oxaliplatin, 5-fluorouracil, and leucovorin (FOLFOX regimen). Med. Oncol. 28:S274–9; 2011. Edge, S.B.; Byrd, D.R.; Compton, C.C.; et al. AJCC cancer staging manual (6th ed). New York: Springer; 2010. International Commission on Radiation Units and Measurements. Prescribing, Recording, and Reporting Photon Beam Therapy. Bethesda, MD, ICRU, 1993. Wambersie, A.; Landberg, T. ICRU Report 62: Prescribing, Recording and Reporting Photon Beam Therapy (Supplement to ICRU Report 50); 1999. Gong, Y.L.; Wang, S.C.; Zhou, L.; et al. Dosimetric comparison using different multileaf collimeters in intensity-modulated radiotherapy for upper thoracic esophageal cancer. Radiat. Oncol. 5:65; 2010. van't Riet, A.; Mak, A.C.; Moerland, M.A.; et al. A conformation number to quantify the degree of conformality in brachytherapy and external beam irradiation: application to the prostate. Int. J. Radiat. Oncol. Biol. Phys. 37:731–6; 1997. Ringash, J.; Perkins, G.; Brierley, J.; et al. IMRT for adjuvant radiation in gastric cancer: a preferred plan? Int. J. Radiat. Oncol. Biol. Phys. 63:732–8; 2005.
19. Minn, A.Y.; Hsu, A.; La, T.; et al. Comparison of intensity-modulated radiotherapy and 3-dimensional conformal radiotherapy as adjuvant therapy for gastric cancer. Cancer 116:3943–52; 2010. 20. Boda-Heggemann, J.; Hofheinz, R.D.; Weiss, C.; et al. Combines adjuvant radiochemotherapy with IMRT/XELOX improves outcome with low renal toxicity in gastric cancer. Int. J. Radiat. Oncol. Biol. Phys. 75:1187–95; 2009. 21. Dahele, M.; Skinner, M.; Schultz, B.; Cardoso, M.; Bell, C.; Ung, Y.C. Adjuvant radiotherapy for gastric cancer: a dosimetric comparison of 3-dimensional conformal radiotherapy, tomotherapy® and conventional intensity modulated radiotherapy treatment plans. Med. Dosim. 35:115–21; 2010. 22. Marcus Jr R.B.; Million, R.R. The incidence of myelitis after irradiation of the cervical spinal cord. Int. J. Radiat. Oncol. Biol. Phys. 19:3–8; 1990. 23. Holt, A.; van Vroegindeweij, C.; Mans, A.; et al. Volumetric-modulated arc therapy for stereotactic dose radiotherapy of lung tumors: a comparison with intensity modulated radiotherapy techniques. Int. J. Radiat. Oncol. Biol. Phys. 81:1560–7; 2011. 24. Bertelsen, A.; Hansen, C.R.; Johansen, J.; et al. Single arc volumetric modulated arc therapy of head and neck cancer. Radiother. Oncol. 95:142–8; 2010. 25. Guckenberger, M.; Richter, A.; Krieger, T.; et al. Is a single arc sufficient in volumetric-modulated arc therapy (VMAT) for complex-shaped target volumes? Radiother. Oncol. 93:259–65; 2009. 26. Verbakel, W.F.; Cuijpers, J.P.; Hoffmans, D.; et al. Volumetric intensitymodulated arc therapy vs. conventional IMRT in head-and-neck cancer: a comparative planning and dosimetric study. Int. J. Radiat. Oncol. Biol. Phys. 74:252–9; 2009. 27. Shaw, E.; Scott, C.; Souhami, L.; et al. Single dose radiosurgical treatment of recurrent previously irradiated primary brain tumors and brain metastases: final report of RTOG protocol 90-05. Int. J. Radiat. Oncol. Biol. Phys. 47:291–8; 2000. 28. Huchet, A.; Caudry, M.; Belkacemi, Y.; et al. Volume-effect and radiotherapy part two: volume-effect and normal tissue. Cancer Radiother. 7:353–62; 2003. 29. Lefkopoulos, D.; Dejean, C.; El-Balma, H.; et al. Determination of dose-volumes parameters to characterise the conformity of stereotactic treatment plans. In: XIIIth Intern. Conf. on: Computers in Radiation Therapy, [XIIIth ICCR, Heidelberg, Germany]. 356–8; 2000. 30. Feuvret, L.; Noel, G.; Mazeron, J.J.; Bey, P. Conformity index: a review. Int. J. Radiat. Oncol. Biol. Phys. 64:333–42; 2006.