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Abstract. – OBJECTIVE: To compare volu-metric modulated arc therapy (VMAT) and in-tensity-modulated radiation therapy (IMRT) for the treatment of Graves’ ophthalmopathy (GO) based on the dosimetric data.

PATIENTS AND METHODS: 19 patients diag-nosed with GO were recruited in this study. For each patient, a dual-partial-arc VMAT plans and a 7-fixed-field IMRT plans were replanned. Do-simetric parameters of the targets and organs at risk (OARs) originated from the two kinds of plans were compared and analyzed.

RESULTS: Homogeneity index (HI) was superi-or in IMRT plans compared with VMAT (p=0.0014) but there was no significant statistical difference in conformity index (CI) between them (p=0.0673). IMRT plans revealed advantage in the OARs pro-tection especially for the left and right lenses, optic nerves and eyeballs (p<0.05).

CONCLUSIONS: VMAT and IMRT are both fea-sible techniques in radiotherapy in GO from the perspective of dosimetric parameters. Homoge-neity and OAR protection were slightly superior in IMRT plans compared with VMAT plans.

Key Words:Intensity-modulated radiation therapy, Volumet-

ric modulated arc therapy, Graves’ ophthalmopa-thy, Dose.

IntroductionGraves’ ophthalmopathy (GO), also called thy-

roid eye disease or thyroid-associated ophthalmop-

athy (TAO), is an autoimmune orbital inflammato-ry pathology closely related to thyroid diseases1,2. Based on the severity and activity of GO, there are surgery, systemic therapy, radiotherapy and oth-er treatment methods to be chosen for relieving symptoms or curing the benign disease3. The man-agement of GO is usually based on the use of corti-costeroids or orbital irradiation4. Orbital irradiation can be applied to patients with moderate-to-severe GO5. Reports6-9 have demonstrated a 67% overall good-to-excellent response rate with orbital RT. Marquez et al10 studied 197 patients subjected to orbital irradiation. Staar et al4 proved that radiation therapy with or without corticosteroids may lead to an improvement of exophthalmos and eye muscle function in 50-60% of patients whereas the ame-lioration in soft tissue reactions may be up to 70%. The ophthalmic index was improved in 96% of the irradiated patients10. Matthiesen et al11 found that the pre-radiotherapy symptoms were improved in 84.2% of the 211 study participants with GO.

Orbital radiotherapy remains an important method in the treatment of GO12. In radiotherapy, lateral opposing fields (LOF), three-dimensional conformal radiotherapy (3D-CRT), and intensi-ty-modulated radiation therapy (IMRT) are all al-ternative techniques over the past years. With bet-ter target coverage, conformity and homogeneity compared with other ways, IMRT has been widely applied gradually13-15. Volumetric modulated arc

European Review for Medical and Pharmacological Sciences 2020; 24: 3898-3906

S.-C. WANG1, J. WU2, X.-Q. XIE3, X.-L. LIU1, Y. LUO1, F. WANG1, Z.-P. LI1, B.-L. QU4, J.-B. KANG5, D.-B. WU6, W.-M. LI7, R.-Y. WANG8

1Department of Radiation Oncology, Cancer Center, West China Hospital, West China Medical School, Sichuan University, Chengdu, P.R. China2Department of Outpatient West China Hospital, Chengdu, P.R. China3Department of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan, P.R. China4Department of Radiotherapy, Chinese PLA General Hospital, Beijing, P.R. China5Department of Radiotherapy, The Sixth Medical Center of PLA General Hospital, Beijing, P.R. China6Cancer Hospital, Ansteel Group Hospital, Anshan, Liao Ning, P.R. China7Precision Medicine Center West China Hospital, Sichuan University, Chengdu, P.R. China8Department of Medical Oncology, Affiliated Zhongshan Hospital of Dalian, University, Dalian China

Shi Chao Wang and Juan Wu contributed equally to this work

Corresponding Authors: Feng Wang, MD; e-mail: wangfeng5024@126.comBao Lin Qu, MD; e-mail: qubl6212@sina.com

Comparison of IMRT and VMAT radiotherapy planning for Graves’ ophthalmopathy basedon dosimetric parameters analysis

Comparison of IMRT and VMAT radiotherapy planning for Graves’ ophthalmopathy

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therapy (VMAT) has been used for the treatment of several diseases16-18. Studies on comparing IMRT and VMAT for the treatment of GO are lacking. In this study, we compared the plan quality of fixed-beams IMRT with that of dual-partial-arc VMAT to investigate whether VMAT could produce better target dose distribution and normal tissue protec-tion for treatment of GO compared with IMRT.

Patients and Methods

Nineteen patients (males: 6, females: 13) diag-nosed with GO retrospectively were selected and recruited in this study between March 2018 and May 2019 were treated with orbital radiotherapy.

This protocol of this study was approved by the Medical Ethics Committee of west China hos-pital of sichuan university. The written informed consent of all participants was obtained.

Each patient was immobilized with head and neck thermoplastic cast in the supine position.

With comfortable and repeatable immobiliza-tion, they underwent computed tomography (CT) scanning with slice thickness 3 mm for image ac-quisition and target contouring. The gross tumor volume (GTV) and clinical target volume (CTV), which were equal, included the retro-orbital fat-ty spaces together with the main bulk, origins and insertions of the extra-ocular muscles. The organs-at-risk (OARs), including right and left lenses, eyeballs, optic nerves, optic chiasm, were outlined in the CT images. A 2 mm concentric margin around GTV was created to generate the planning target volume (PTV). Target volume was contoured by oncologists in Eclipse Treatment Planning System (Varian Medical System, Ver-sion 13.5, Palo Alto, CA, USA). For all patients, the target dose was prescribed as 21.2 Gy deliv-ered in 10 fractions achieved to 95% coverage of the PTV. The beam angle for the dual-partial-arc VMAT plans was from 240° to 120° clockwisely and from 120° to 240° anticlockwisely. Gantry

Figure 1. Fields arrangement and dose distribu-tion of one typical patient. A, 7-fixed-beam IM-RT, B, dual-partial-arc VMAT.

A

B

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angle of 7-Fixed-beam IMRT plans was arranged as 0°, 30°, 70°, 120°, 240°, 290°, 330°. There were minor adjustments as clinical needed (Figure 1).

During optimization procedures, dose restric-tions and weightings of CTV, PTV, three rings of PTV (extending 0.5 cm from PTV in turn), lenses, and the rings of lenses (extending 0.5 cm from the lenses) were set to control the dose in target vol-ume and OARs. The right and left lenses, planning organs at risk volume (PRV) lens , right and left optic nerves, right and left temporal lobes, right and left eyeballs were contoured as OARs for each individual. Conformity index (CI), homogeneity index (HI) and dosimetric parameters, including the minimum dose (Dmin), mean dose (Dmean), maximum dose (Dmax), D5 (dose received by the maximal 5% of the target), D95 (dose received by the maximal 95% of the target) of PTV, the mean and maximum of lenses, the maximum of optic nerves eyes and temporal lobes were recorded in the study. We applied the formula CI = Vref

2/ VPTV ×

Vpre (VPTV: the volume of PTV; Vpre: the treatment volume encompassed by the prescribed isodose lines; Vref: the overlap volume of the PTV and pre-scribed isodose lines) and HI = D5/D95 (D5 and D95: the dose received by the maximal 5% and 95% of the PTV respectively)19.

Statistical AnalysisA statistical analysis of the DVHs of target vol-

umes and critical organs was performed. All data generated by the two planning were analyzed by Student t-test using Statistical Package for the So-cial Sciences program (version 24.0, SPSS, IBM Corp., Armonk, NY, USA). The p-value < 0.05 was defined as having statistical significance.

Results

The median PTV volume of all 19 orbits was 55.26 cc (range: 41.7-80.9 cc).

Figure 2. Dose-volume histograms of two plans resulted from one selective patient. A, Comparison of PTV, B, comparison of right and left lens.

B

A

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PTV CI HI Dmin Dmax Dme-an D5

I V I V I V I V I V I V

1 0.596 0.715 1.081 1.110 1758.6 1588.3 2400.0 2465.7 2218.6 2254.0 2290.3 2353.22 0.800 0.788 1.094 1.101 841.1 911.4 2509.4 2676.4 2238.8 2225.9 2318.9 2333.33 0.753 0.858 1.093 1.058 1846.3 1900.2 2439.3 2335.7 2235.6 2190.8 2317.1 2244.24 0.656 0.430 1.100 1.180 1553.6 1135.2 2369.9 2573.1 2246.2 2357.9 2330.5 2497.95 0.686 0.400 1.135 1.237 1632.3 992.5 2460.5 2720.4 2291.8 2439.5 2407.2 2623.96 0.750 0.360 1.103 1.420 1109.6 864.4 2398.3 3198.6 2243.7 2712.7 2338.9 3004.17 0.628 0.387 1.124 1.280 1526.6 1124.7 2464.1 2856.5 2265.6 2513.6 2383.4 2713.58 0.709 0.448 1.132 1.228 1466.6 1298.1 2466.8 2697.8 2293.2 2425.0 2399.6 2600.29 0.661 0.371 1.136 1.343 1430.7 928.6 2386.6 2429.5 2160.9 2076.8 2275.2 2279.210 0.538 0.746 1.058 1.123 975.1 912.2 2679.8 2515.7 2273.9 2373.8 2241.0 2381.311 0.639 0.732 1.082 1.095 1729.6 1625.6 2427.0 2490.7 2219.9 2239.1 2292.8 2320.712 0.758 0.410 1.099 1.287 1259.4 793.4 2323.5 2375.9 2189.0 2091.7 2270.4 2270.913 0.708 0.601 1.088 1.212 1716.3 1413.1 2380.0 2652.3 2226.4 2395.8 2307.2 2566.014 0.596 0.761 1.090 1.078 1441.2 1381.4 2392.7 2346.1 2227.3 2214.3 2310.2 2284.215 0.591 0.772 1.081 1.073 1703.6 1623.6 2341.0 2336.9 2212.3 2212.8 2292.8 2275.016 0.021 0.746 1.088 1.082 1676.4 1761.9 2420.1 2381.4 2225.1 2221.3 2305.5 2293.317 0.643 0.733 1.075 1.083 1858.2 793.1 2331.8 2385.3 2199.7 2200.8 2278.3 2296.718 0.603 0.624 1.092 1.192 1541.7 1309.7 2481.3 2680.5 2217.2 2362.9 2315.6 2527.319 0.599 0.626 1.080 1.137 1695.2 1520.1 2394.3 2625.7 2216.1 2276.6 2290.3 2409.0Average 0.628 0.606 1.096 1.175 1513.8 1256.7 2424.5 2565.5 2231.6 2304.5 2314.0 2435.5 (mean ± SD) ±0.163 ±0.172 ±0.021 ±0.103 ±286.1 ±349.2 ±80.2 ±218.0 ±33.2 ±152.9 ±43.4 ±197.6p-value 0.0673 0.0014 0.0008 0.011 0.027 0.007

Table I. Summary of evaluated data for the two kinds of plans on PTV.

CI: conformity index; HI: homogeneous index; PTV: planning target volume; I: intensity-modulated radiation therapy; V: Volumetric modulated arc therapy; D5= dose encompassing 5% of the volume; Dmin= irradiation dose of targets received by minimal dose; Dmax= irradiation dose of targets received by maximal dose; Dmean= irradiation dose of targets received by mean dose.

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Table I shows the evaluated data on the PTV between the two kinds of plans. Mean CI gen-erated by VMAT and IMRT were 1.83 and 1.53, respectively. There was no significant statistical difference in CI when comparing the two treat-ment techniques (p=0.0673, p>0.05).

Mean HI generated by them were 1.17 and 1.10, respectively. A superior HI was observed in IMRT compared with VMAT (p=0.0014). VMAT generated a lower Dmin (p=0.0009), a higher Dmax (p=0.0105) and Dmean (p=0.0276) than IMRT. No significant statistical difference in the dose received by the maximal 95%, though the dose received by the maximal 5% of the PTV was higher in VMAT.

OARs dose sparing distribution was shown in Table II. Similar to PTV, VMAT made high-er dose distribution in the left lens (Dmax: p=0.0246, Dmean: p=0.0114), and higher Dmax in the right lens (p=0.0463). The rings of both lens received a higher Dmax (left: p=0.0161 and right: 0.0034). It is same in the optic nerve (left: p=0.0050 and right: p=0.0225) and eyes (left: p=0.0045 and right: p=0.0031). No differ-ence was found in the temporal lopes between two techniques (p=0.1786 and p=0.0895).

Figure 3 illustrated the comparison of the MUs used in the two kinds of plan. The MUs showed that the total MU usage increased significantly as the number of beams used in IMRT plans com-pared with the VMAT plans used. The data on the IMRT plan were about twice than the data on VMAT.

Discussion

GO is one of the common complications of hyperthyroidism. With high incident rate in to-tal number of patients, it has a great impact on the quality of life of patients. In addition to the symptoms of hyperthyroidism, patients with GO are accompanied by ocular protrusion, conjunc-tival hyperemia, and corneal ulcer1,2,20. Smoking cessation, management of hyperthyroidism, glu-cocorticoids taking, orbital radiotherapy, and or-bital surgery are current effective treatment meth-ods3,10-13. Lateral opposing fields (LOF), 3D-CRT, and IMRT are all alternative radiotherapy tech-niques for the disease over the past years. IMRT has been playing an important role due to its bet-ter target coverage, conformity and homogeneity compared with other ways13-15. As a new imple-mentation of IMRT, VMAT showed its advantag-

es in radiotherapy of several diseases like breast cancer, prostate cancer, cervical esophageal car-cinoma21-24, such as better target coverage, better homogeneity and conformal index, and sharper dose gradient. However, it did not present the same advantages in all diseases. For instance, there were some differences in OAR protection in different studies. VMAT increased the low dose regions of the lung, heart in treatment for patients undergone breast-conserving operation22, while providing particularly low doses to the brain and optical system in total scalp irradiation21. As for GO, San-Miguel et al25 revealed that VMAT gen-erated superior CI and showed significant bene-fit in OAR sparing compared with 3D-CRT and LOF.

In this work, we found that both of the two kinds of plans can meet the clinical requirements and achieve equivalent conformality for targets. IMRT generated superior HI of PTV and has lower maximum dose and mean dose comparing with VMAT. It might be related to the type of ac-celerator. This study used Varian’s Edge linear accelerator with multi-leaf collimator (MLC) as thin as 2.5 mm, which weakened the advantages of VMAT in intensity modality to a certain ex-tent. We applied dual partial arc VMAT to reduce the normal tissue dose sparing. It is investigated that VMAT increased the dose in OARs includ-ing lenses, optic nerve and eyes. IMRT produced better OARs protection due to the more segments created by IMRT. However, the increased dose in normal tissue was clinically negligible and VMAT had similar conformal coverage of the PTV compared with IMRT. Besides, considering the decreased MUs of VMAT plans, VMAT is a more suitable choice for clinical centers that have great number of patients undergoing radiotherapy. This study has also some limitations. Treatment time (TT, beginning from the loading first beam and ending at the last beam-on finished) was not concluded in the results. The number of beams of IMRT plan may be considered 5 or 9.

We found that VMAT plans usually reduce MU usage compared to IMRT plans; Wollf et al26 and Yoo et al27 demonstrated the same con-clusion. One explanation may be that the control pints (CPs) of IMRT plans were much more than other techniques due to the sliding and window technique used, based on the Varian treatment planning system (TPS). Admittedly, higher MU has its drawbacks, such as the potential increase in total body dose because of scattering and leak-age from MLCs28.

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Lt Lens Rt Lens Lt Lens Rt Lens Lt temporal Rt temporal Lt optic Rt optic Lt eyeball Rt eyeball PRV PRV lope lope nerve nerve

Dmax Dmean Dmax Dmean Dmax Dmax Dmax Dmax Dmax Damx Dmax Dmax

I V I V I V I V I V I V I V I V I V I V I V I V

1 552.7 521.5 409.5 436.2 511.5 517.9 373.4 415.9 1042.0 1056.6 1059.4 1076.9 2301.2 2405.8 2260.4 2354.1 2303.1 2387.3 2317.2 2401.6 2278.6 2424.3 2305.9 2417.0 2 553.5 561.1 432.9 450.6 585.9 528.9 474.6 442.1 999.8 965.7 1065.0 923.9 2119.2 2165.3 2188.4 2251.7 2308.9 2219.8 2332.3 2359.8 2311.4 2457.5 2300.9 2476.7 3 604.8 556.4 485.4 474.5 576.4 515.9 481.4 394.7 936.3 903.6 1012.9 943.1 2240.6 2250.1 2133.0 2149.1 2311.4 2288.1 2303.4 2263.0 2310.6 2263.1 2341.8 2250.9 4 507.9 627.0 442.5 478.1 550.3 589.9 456.2 462.5 897.2 1054.4 907.7 1025.5 2324.1 2351.9 2281.5 2379.4 2345.1 2573.1 2353.3 2531.2 2298.2 2538.1 2288.3 2506.4 5 518.9 582.9 414.5 449.1 539.5 639.8 432.7 458.6 959.0 1119.7 936.9 1125.2 2352.7 2499.9 2386.5 2466.4 2431.5 2707.3 2423.1 2685.0 2294.1 2592.7 2300.0 2541.2 6 594.2 652.6 500.3 515.8 595.1 669.9 470.3 507.7 948.9 1341.1 968.3 1335.9 2222.8 2733.0 2319.7 2783.3 2387.8 3007.8 2368.6 3090.0 2288.5 2948.1 2315.6 3050.1 7 619.2 805.3 440.7 576.7 599.9 664.6 430.6 447.2 1416.3 2140.7 1668.7 2045.4 2320.5 2517.7 2240.7 2458.1 2378.1 2730.3 2384.8 2720.1 2410.9 2738.3 2350.1 2783.0 8 520.1 611.7 406.8 459.3 567.1 574.6 408.8 458.9 1238.9 1965.9 1428.0 1380.4 2261.5 2421.4 2283.2 2446.6 2380.6 2573.0 2390.5 2545.9 2372.0 2651.3 2308.7 2606.5 9 582.2 582.1 405.3 419.3 595.2 558.3 405.3 416.3 1590.6 1734.0 1476.8 1681.6 2135.9 2159.4 2128.0 2022.5 2258.9 2325.3 2270.9 2169.5 2289.1 2265.9 2243.2 2330.710 754.7 624.9 441.9 428.4 588.7 546.2 492.1 460.8 1532.8 1342.3 1001.4 941.5 2756.4 2307.3 2510.9 2319.9 2480.1 2401.6 2511.8 2375.2 2437.0 2360.0 2421.3 2384.611 600.5 601.0 456.3 467.3 619.1 623.8 456.6 468.7 1027.6 1035.0 1070.9 1101.2 2271.3 2314.4 2228.6 2285.3 2297.3 2360.4 2310.6 2348.6 2280.7 2332.0 2291.4 2300.312 568.7 637.0 426.8 426.2 561.7 561.8 442.6 375 1423.2 2011.0 1416.1 1821.2 2187.1 2106.2 2247.6 2213.2 2279.4 2223.0 2296.5 2263.4 2241.6 2306.2 2237.4 2292.413 594.4 638.9 425.7 436.9 586.0 606.4 448.1 446.4 1704.4 2093.8 1406.7 1756.4 2208.9 2424.2 2290.2 2461.5 2312.7 2548.2 2326.8 2554.4 2303.7 2628.3 2314.9 2589.414 503.0 556.0 373.7 481.4 504.4 537.7 368.1 432.9 1029.2 1014.0 1068.4 1098.6 2292.5 2290.4 2315.3 2283.4 2328.5 2307.1 2318.7 2319.0 2290.6 2320.2 2292.0 2326.415 553.7 580.7 456.5 475.5 523.8 616.8 418.0 499.1 1101.5 1003.7 992.8 1036.7 2304.3 2245.1 2276.5 2197.2 2314.1 2317.6 2300.4 2284.6 2317.1 2293.7 2281.1 2501.216 451.7 523.4 358.1 444.2 466.3 531.6 386.7 434.4 1183.8 990.8 1058.0 1093.9 2306.9 2281.3 2288.9 2268.2 2317.9 2310.3 2327.1 2309.3 2298.1 2282.0 2307.3 2301.217 501.0 490.5 431.8 409.5 507.2 531.6 390.5 402.7 1009.1 980.4 959.3 1050.5 2200.0 2271.2 2263.3 2290.5 2292.7 2356.3 2293.5 2342.6 2280.1 2323.1 2277.0 2316.618 359.4 723.9 267.9 579.5 440.4 770.0 286.9 600.4 984.1 1252.5 1029.7 1316.5 2392.5 2459.4 2386.4 2395.1 2390.4 2626.8 2369.6 2583.4 2265.0 2540.1 2275.0 2615.519 546.8 784.5 446.8 654.7 512.9 778.2 424.7 599.1 1174.4 1491.2 1171.0 1512.2 2305.5 2391.1 2304.8 2406.4 2299.7 2458.0 2326.0 2557.0 2310.2 2387.1 2279.5 2499.3Aver-age 552.0 613.8 422.3 477.0 549.0 598.1 423.6 459.1 1168.4 1341.9 1142.0 1277.2 2289.7 2347.1 2280.7 2338.5 2337.8 2459.0 2343.4 2458.1 2309.3 2455.4 2301.7 2478.4(mean ±SD) ±78.8 ±83.5 ±50.2 ±63.5 ±48.9 ±78.6 ±49.1 ±48.9 ±246.8 ±430.9 ±221.0 ±336.0 ±133.6 ±147.7 ±87.8 ±159.4 ±56.3 ±204.5 ±56.2 216.4 ±48.0 ±188.7 ±40.1 ±198.0p-value 0.025 0.011 0.046 0.095 0.016 0.003 0.178 0.090 0.005 0.023 0.005 0.003

Table II. Summary of evaluated data for the two kinds of plans on PTV.

Abbreviations: OARs: organs at risk; PRV: homogeneous index; PTV: planning target volume; I: intensity-modulated radiation therapy; V: Volumetric modulated arc therapy; D5= dose encompassing 5% of the volume; Dmin= irradiation dose of targets received by minimal dose; Dmax= irradiation dose of targets received by maximal dose; Dmean= irradiation dose of targets received by mean dose.

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In addition, orbital decompression has been used not only as a primary mode of therapy but also as treatment after failure of corticosteroid or orbital radiation therapy29-32. For active, inflam-matory phase, fibrotic state, some patients re-ceived orbital decompression.

Conclusions

VMAT and IMRT are both feasible RT tech-niques for GO based on the retrospective dosim-etric analysis. both of IMRT and VMAT are good treatments for Graves’ ophthalmopathy. Homoge-neity and OAR protection was slightly superior in IMRT plans compared with VMAT, while a sig-nificant reduction in MU was observed in the us-age of VMAT. We believe VMAT might become a popular treatment for GO in the future.

AcknowledgmentsThis project is funded by the Research and Data on the Evaluation Method of Stereotactic Radiotherapy Equipment (Subject No. 2017YFC0113701).

Research and Development of tumor real-time monitor-ing molecular diagnostic products based on liquid biopsy -- a major Science and Technology Project of Guangdong Province 2019B020232003

Dalian Municipal Science and Technology Innovation Projects (2018 j12sn063): a new method for the detection op-tical flow control chip peripheral blood tumor cells research Science and Technology Innovation Project of Dalian City (No: 2018 j12sn063).

Liaoning Provincial Key Research and Development Plan Project Name: construction project no. 2018225050 fat

stem cell storage and application platform no. 2018020143-301 Project Name of Natural Science Foundation of Liaoning Province: basic research on the regulation effect of Gegen-qinlian decoction based on 16S rRNA gene on intestinal flora of mice with radioactive enteritis project No. 20180550798; Contract No. 2018011225-301 Nature Foundation Guidance Program Ph.D Initiation Fund Project Name: the relation-ship between fluoxetine in inhibiting astrocytoma growth and TRPC1 research project No. 20180551182 Contract No. 2018011575-301.The protocol of this study was approved by the medical ethics committee of west China hospital of sichuan uni-versity. The written informed consent of all participants was obtained.

Conflict of InterestsThe authors declare that they have no conflict of interests.

References

1) Burch hB, Wartofsky L. Graves' ophthalmopathy: current concepts regarding pathogenesis and management. Endocr Rev 1993; 14: 747-793.

2) Bahn rs. Graves' ophthalmopathy. N Engl J Med 2010; 362: 726-738.

3) san MigueL i, arenas M, carMona r, rutLLan J, Medina-rivero f, Lara P. Review of the treatment of Graves' ophthalmopathy: the role of the new radiation techniques. Saudi J Ophthalmol 2018; 32: 139-145.

4) staar s, eich ht, seegenschMiedt Mh. Graves’ or-bitopathy. In: Seegenschmiedt MH, Makoski. HB, Trott KR, Brady LW, eds. Radiotherapy for

Figure 3. Paired data on MUs of 19 patients recruited in this study.

Comparison of IMRT and VMAT radiotherapy planning for Graves’ ophthalmopathy

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non-malignant disorders. Berlin: Springer; 2008: 469-486.

5) BartaLena L, BaLdeschi L, dickinson a, eckstein a, kend-aLL-tayLor P, Marcocci c, Mourits M, Perros P, BoBoridis k, Boschi a, currò n, dauMerie c, kahaLy gJ, krassas ge, Lane cM, Laz-arus Jh, Marinò M, nardi M, neoh c, orgiazzi J, Pearce s, Pinchera a, Pitz s, saLvi M, siveLLi P, stahL M, von arx g, Wiersinga WM, Euro-pean Group on Graves' Orbitopathy (EUGOGO). Consensus statement of the European Group on Graves’ orbitopathy (EUGOGO) on management of GO. Eur J Endocrinol 2008; 158: 273-285.

6) Petersen ia, kriss JP, McdougaLL, ir, donaLdson ss. Prognostic factors in the radiotherapy of Graves’ ophthalmopathy. Int J Radiat Oncol Biol Phys 1990; 19: 259-264.

7) hurBLi t, char dh, harris J, Weaver k, greensPan f, sheLine g. Radiation therapy for thyroid eye diseases. Am J Ophthalmol 1985; 99: 633-637.

8) Beckendorf v, MaaLouf t, george JL, Bey P, LecLere J, LuPorsi e. Place of radiotherapy in the treatment of Graves’ orbitopathy. Int J Radiat Oncol Biol Phys 1999; 43: 805-815.

9) Wiersinga WM, sMit t, schuster-uittenhoeve aL, van der gaag r, koornneef L. Therapeutic outcome of prednisone medication and of orbital irradiation in patients with Graves’ ophthalmopathy. Ophthal-mologica 1988; 197: 75-84.

10) Marquez sd, PharM BLL, McdougaLL ir, katkuri s, Levin Ps, MacManus M, donaLdson ss. Long-term results of irradiation for patients with progressive Graves ophthalmopathy. Int J Radiat Oncol Biol Phys 2001; 51: 766-774.

11) Matthiesen c, thoMPson Js, thoMPson d, farris B, WiLkes B, ahMad s, herMan t, Bogardus c Jr. The efficacy of radiation therapy in the treatment of Graves' orbitopathy. Int J Radiat Oncol Biol Phys 2012; 82: 117-123.

12) Ruchała M1, heRnik a, Zybek a. Orbital radiothera-py in the management of Graves' orbitopathy-cur-rent state of knowledge. Endokrynol Pol 2014; 65: 388-396.

13) Marcos JiMénez f, deL cerro PeñaLver e, díaz gaveLa a, couñago Lorenzo f, MoLina LóPez y, Pardo Pérez e. Comparative dosimetric analysis (IMRT vs 3DRTC) for Graves’ ophthalmopathy irradiation. Rep Pract Oncol Radiother 2013; 18: S293.

14) Li yJ, Luo y, he WM, Li P, Wang f. Clinical out-comes of graves' ophthalmopathy treated with in-tensity modulated radiation therapy. Radiat Oncol 2017; 12: 171.

15) Lee vh, ng sc, choi cW, Luk My, Leung tW, au gk, kWong dL. Comparative analysis of dosim-etric parameters of three different radiation tech-niques for patients with Graves' ophthalmopathy treated with retro-orbital irradiation. Radiat Oncol 2012; 7: 199.

16) treutWein M, hiPP M, koeLBL o, doBLer B. Volu-metric-modulated arc therapy and intensity-mod-ulated radiation therapy treatment planning for prostate cancer with flattened beam and flatten-

ing filter free linear accelerators. J Appl Clin Med Phys 2017; 18: 307-314.

17) yang h, feng c, cai Bn, yang J, Liu hx, Ma L. Comparison of three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and volumetric-modulated arc therapy in the treatment of cervical esophageal carcinoma. Dis Esophagus 2017; 30: 1-8.

18) iorio gc, franco P, gaLLio e, Martini s, arcadiPane f, Bartoncini s, rondi n, gigLioLi fr, aLa a, airoLdi M, donadio M, de sanctis c, casteLLano i, ricardi u. Volumetric modulated arc therapy (VMAT) to deliver nodal irradiation in breast cancer patients. Med Oncol 2017; 35: 1.

19) Wang sc, Wang x, he yB, zhao yq, Li t, ai P, xu f, Lu y. A dosimetric comparison of the fixed-beam IMRT plans using different leaf width of multileaf collimators for the intermediate risk prostate can-cer. Radiat Phys Chem 2016; 127: 210-221.

20) kotWaL a, stan M. Current and future treatments for Graves' disease and Graves' ophthalmopathy. Horm Metab Res 2018; 50: 871-886.

21) ostheiMer c, hüBsch P, Janich M, gerLach r, vorder-Mark d. Dosimetric comparison of intensity-modu-lated radiotherapy (IMRT) and volumetric modu-lated arc therapy (VMAT) in total scalp irradiation: a single institutional experience. Radiat Oncol J 2016; 34: 313-321.

22) sun ht, yang rJ, Jiang P, Jiang WJ, Li Jn, Meng n, Wang JJ. [Dosimetric analysis of volumetric modulated arc therapy and intensity modulated radiotherapy for patients undergone breast-con-serving operation]. Beijing Da Xue Xue Bao Yi Xue Ban 2018; 50: 188-192.

23) yang h, feng c, cai Bn, yang J, Liu hx, Ma L. Comparison of three-dimensional conformal radiation therapy, intensity-modulated radiation therapy, and volumetric-modulated arc therapy in the treatment of cervical esophageal carcinoma. Dis Esophagus 2017; 30: 1-8.

24) cakir a, akgun z, fayda M, agaogLu f. Comparison of three dimensional conformal radiation therapy, intensity modulated radiation therapy and volu-metric modulated arc therapy for low radiation exposure of normal tissue in patients with pros-tate cancer. Asian Pac J Cancer Prev 2015; 16: 3365-3370.

25) san-MigueL i, carMona r, Luque L, caBrera r, LLoret M, rutLLan f, Lara Pc. Volumetric Modulated Arc Therapy (VMAT) make a difference in retro-orbit-al irradiation treatment of patients with bilateral Graves’ ophthalmopathy. Comparative analysis of dosimetric parameters from different radiation techniques. Rep Pract Oncol Radiother 2016; 21: 435-440.

26) WoLff d, stieLer f, WeLzeL g, Lorenz f, aBo-Madyan y, Mai s, herskind c, PoLednik M, steiL v, Wenz f, Lohr f. Volumetric modulated arc therapy (VMAT) vs. serial tomotherapy, stepand-shoot IMRT and 3D-conformal RT for treatment of prostate can-cer. Radiother Oncol 2009; 93: 226-233.

S.-C. Wang, J. Wu, X.-Q. Xie, X.-L. Liu, Y. Luo, et al

3906

27) yoo s, Wu qJ, Lee Wr, yin ff. Radiotherapy treat-ment plans with RapidArc for prostate cancer involving seminal vesicles and lymph nodes. Int J Radiat Oncol Biol Phys 2010; 76: 935-942.

28) haLL eJ. Intensity-modulated radiation therapy, protons, and the risk of second cancers. Int J Radiat Oncol Biol Phys 2006; 65: 1-7.

29) Mourits MP, koornneef L, Wiersinga WM, PruMMeL Mf, Berghout a, van der gaag r. Orbital decom-pression for Graves' ophthalmopathy by inferome-dial, by inferomedial plus lateral, and by coronal approach. Ophthalmology 1990; 97: 636-641.

30) LaMBerg B-a, granne B, toMMiLa v, PeLkonen r, rinne J, LiesMaa M, väLiMäki M. Orbital decom-pression in endocrine exophthalmos of Graves' disease. Acta Endocrinol 1985; 109: 335-340.

31) Mccord cd Jr. Current trends in orbital decom-pression. Ophthalmology 1985; 92: 21-33.

32) BartaLena L, Marcocci c, Bogazzi f, Panicucci M, Bruno-Bossio g, cantini r, LePri a, tusini g, Pinchera a. Orbital decompression for severe Graves' ophthalmopathy: results of a three-wall operativetechnique. J Neurosurg Sci 1989; 33: 323-327.