Dosimetric evaluation of three commercial radiotherapy planning systems for lung cancer and nasopharyngeal carcinoma cases

Purpose: To identify planning systems and techniques suitable for different sites tumors by analyzing dosimetric differences using three commercial radiotherapy planning systems: Tomotherapy, Monaco and Eclipse. Methods: We retrospectively analyzed 20 lung cancer and 8 nasopharyngeal carcinoma (NPC), and each patient plans were designed using the three systems. The dose distribution of the target and organs at risk (OARs) were compared, and monitor unit (MU) and treatment time were also evaluated. Results: For lung cancer, mean dose of PGTV, PTV1 and PTV2 in Monaco and Tomo plans were lower than Eclipse plan. PTV2 CI in Monaco and Eclipse plans were better than Tomo plans (p=0.002, p=0.022). Monaco and Tomo plans were better than Eclipse plan regarding to mean dose and V 15Gy of lungs; the lowest lungs V 20Gy and V 30Gy were provided by Tomo plan. The esophagus, heart and SpinalCord_03 dose were lowest in Monaco plan, and the maximum dose and V 45Gy of SpinalCord_03 were 592.1cGy and 1.37% lower than Eclipse plan, respectively. For NPC, mean dose of PGTV, PTV1 and PTV2 in Eclipse plan were superior to Tomo plan (p=0.008, p=0.000, p=0.003); PTV2 V 95% in Tomo plan was increased by 1.64% than Eclipse plan. There was no signicant difference between Monaco and Eclipse plans. Tomo plan showed better spinal cord and brainstem protection, with spinal cord max dose 249.38cGy lower than Eclipse plan and 555cGy lower than Monaco plan, respectively. Conclusion: Although the three plans reected their respective advantages in different aspects, in general, the Monaco plan (VMAT) was the best choice for lung cancer, and for the more advanced nasopharyngeal carcinoma, the Tomo plan (HT) was superior to the other two plans.


Introduction
Mortality due to cancer is gradually increasing. An analysis of death causes in 195 countries from 1980 to 2017 showed that cancers accounted for 23.3% of non-communicable disease-related deaths, with the largest number of deaths caused by tracheal carcinoma, bronchogenic carcinoma, and lung cancer (188 million people) [1] .Morbidity and mortality analysis of 36 cancers in 185 countries revealed that the highest cancer mortality rate was attributable to lung cancer, accounting for 18.4% of total cancer deaths [2] . The regional distribution of nasopharyngeal carcinoma (NPC) is very obvious. According to data from international research institutions, 70% of new nasopharyngeal cancer patients (127,000) in 2018 occurred in East and Southeast Asia [3] .
Radiation therapy is an effective treatment for lung cancer and NPC. Intensity-modulated radiation therapy (IMRT) is an important technique to improve target coverage and reduce the dose of organs at risk (OARs) [4] . Based on IMRT, new technologies have been developed: volumetric modulated arc therapy (VMAT) and helical tomotherapy (HT). Kannarunimitet al. identi ed that RapidArc, SmartArc and Tomo (HT) provided more effective treatment than IMRT in lung cancer [9] . RapidArc and SmartArc had the lowest mean dose and the lowest V 20Gy of lung, but there was no signi cant difference between RapidArc and SmartArc. Some studies found RapidArc plans had better lungs sparing, compared to HT and IMRT [10~12] .For head and neck cancers, many studies showed that the VMAT and HT afford better target dose uniformity and coverage than IMRT, however, HT had better OARs sparing than VMAT, such as brainstem and spinal cord [5~8,13~17] . In other studies, the difference between IMRT and VMAT in plan quality found that the difference was not signi cant. The obvious advantage of VMAT was that it reduced the treatment time. Because OARs were always in the beam path of VMAT during the rotation, IMRT was better than VMAT for the small organs closing to tumors, such as optical nerve or lens. [18~21] .The purpose of this study was to compare the dosimetric differences of treatment planning in Tomotherapy, Monaco, and Eclipse for lung cancer and NPC.  were treated with 4D CT after their breathing stabilized, the slice thickness was 5 mm. All NPC patients were scanned with a slice thickness of 3 mm.

Materials And
2.2.1. Lung cancer GTV: the primary tumors and positive lymph nodes. CTV: GTV expansion of 6 mm and involved lymph node areas, CTV1 contained a high-risk lymph node drainage area, and CTV2 contained a low-risk drainage area and supraclavicular drainage area). PTV: GTV/CTV expansion of 5 ~ 10 mm in all direction [22] . More details could be found in RTOG 0615 and studies of Grégoire and Lee [23~24] . The corresponding PTV was externally expanded by 3 mm in the three-dimensional direction of GTVnx, CTV1, and CTV2, and was automatically generated by the planning system.

Plan evaluation
All treatment plans dose was normalized: Target coverage of the Eclipse plan and Monaco plan was normalized to dose coverage of the corresponding target area of the Tomo plan. All the dosimetric parameters were obtained from the dose volume histogram (DVH), with resolution of 0.1 cm and the bin size of 1 cGy.
To assess the dose distribution, Homogeneity index (HI) and conformity index (CI) were used. The calculation formulas were as follows: (see Equations 1 and 2 in the Supplementary Files) D 2% is the minimum absorbed dose covering 2% of the target volume, and D 98% is the minimum absorbed dose covering 98% of the target volume. V Target95% is the target volume covered by 95% of prescription, V Target is target volume, and V body95% is volume covered by 95% prescription. The closer CI value to 1 means better conformity of the plans, and the lower HI value means better homogeneity of radiation distribution. Finally, this study also compares the cumulative monitoring unit (MU) and treatment time of different plans.

Statistical analysis
All the data was analyzed with SPSS 25.0 (SPSS Inc., Chicago, IL, USA). And the analysis of variance was performed on the data that accorded with the normal distribution and the homogeneity of the variance, and the least-signi cant difference test (LSD-t) was also performed. For data that did not meet the normality test, the Friedman rank-sum test was selected and Bonferroni correction was performed for the test results. The difference was considered statistically signi cant at p < 0.05. (In SPSS, if p > 0.05 in the Friedman test, then the three distributions are considered to be no different and no multiple comparative analysis is performed).  Overall, Monaco (VMAT) plan offered better protection for more OARs from lung cancer. Of the three plans, the Tomo plan provided optimal V 20Gy and V 30Gy protection for the lungs, except for V 10Gy .Tomo plan provided the most MU and the longest treatment time for lung cancer cases. The average was 7383 MU, and the treatment time was 6 ~ 12 min. Eclipse plan (RapidArc) had the least MU (620 MU) and treatment time (2 ~ 3 min). Monaco plan (VMAT) the average MU of these plans was 1150 MU, and there was a fair treatment time with the eclipse plan. In summary, the Tomo plan was superior to the IMRT in Eclipse and Monaco plans with respect to target coverage, target high-dose control, CI and HI of the NPC cases in our study. However, the Monaco plan was better than the Eclipse plan in D 1% control of the target (PGTV, PTV1, PTV2) and PGTV homogeneity. Details are shown in Table 4.

OARs
Brainstem and spinal cord dose of Tomo plan were signi cantly lower than those in the other two plans. In details, brainstem mean dose was 1117.39 cGy and 922.38 cGy lower than those in the Eclipse and The Pariod_R_Norm V 35Gy in the Eclipse plan was 14.68% lower than the Tomo plan (p = 0.018).
The body_5 mm V 10Gy for the Eclipse and Monaco plans were 10.5% and 8.2% lower than the Tomo plan, and body_5 mm V 20Gy in the Eclipse plan was 6.76% less than the Tomo plan (p = 0.022). The surplus parameters result was not statistically different among the three plans (all p > 0.05), as detailed in Other les Table 2.

Discussion
This study analyzed dosimetric differences in different disease types of three treatment planning systems, including the VMAT vs RapidArc, and IMRT of Monaco and Eclipse. In order to reduce the difference caused by objective factors, all the plans in our study were done by experienced physicist and approved by radiologists. And the technology is inclined to the clinical protocol of the center.
The results of this study indicated that the Tomo plan (HT) had good target high-dose control for lung cancer and NPC, which was proved by previous studies [5,[13][14][15][16]12] . In lung cancer case, the Tomo plan also reduced the normal lung dose in addition to affording the advantages of high-dose control in the target. Studies have shown that the Tomo plan offered an advantage over lungs V 20Gy [10] . Our study found that Tomo plan still showed advantages over the other two plans with respect to lungs V 30Gy .The results obtained by Jacob et al. [12] have showed that the VMAT plan can improve the protection of normal tissues. The results in our study showed:VMAT plans and RapidArc plans provided good target coverage and better CI while the Monaco plan had better HI than the other two plans. Moreover, Monaco plan was better than the Eclipse plan for protecting most organs. It may be resulted from anisotropic analytical algorithm (AAA)in Eclipse plans, and some studies have shown that AAA may overestimate the dose of low-density tissues (such as lungs) [11,25] , and the Monte Carlo was advantageous for these organizations [26] .
For NPC cases, the Tomo plan showed better dose distribution, target coverage, and protection of OARs for patients with T3, N2 and later stage cancer [5,13−16] .At the same time, the results in this study proved that the Tomo plan provided good protection for most OARs in NPC, especially for the brainstem, PRV-BS, spinal cord, and PRV-SC. But the PRV-ON_L/R maximum dose of the Tomo plan was higher, which was consistent with the results reported by Szu-Huai Lu et al. [26] .This study found that the Eclipse IMRT plan revealed a slight advantage in controlling doses to the Eye_L/R, PRV-O.C, PRV-O.N_L/R, and temporal lobe. Several studies have shown that the Tomo plan is advantageous for protection of the parotid gland [13,16,25] . However, in this study, there were basically no signi cant differences in the protection of the parotid gland in the three plans, which may be related to advanced and the larger target volume of the selected patients. As far as the three planning systems concerned, the Monaco plan (VMAT) provided the optimal plan for the lung cancer case, while Tomo (HT) provided the best plan for advanced NPC. What's more, plans of lung cancer showed VMAT in Monaco performed better than RapidArc of Eclipse, and no signi cant difference was found in IMRT plans of NPC. For the limited NPC cases (8 cases), the difference between VMAT and Rapidarc needed further study.
In China, many hospitals had two or more planning systems. When using automatic planning software in a multi-planning system center, it was necessary to consider the treatment bene ts brought by the combination of treatment planning system and technology. The establishment of an automatic planning model relies on the completion of the plans by experienced physicists. And the choice of radiotherapy techniques for tumors at different sites depends on the clinical practices at the center and related dosimetric studies [27~35] . In this study, we investigated the appropriate systems and technologies for the lung cancer and NPC, as a reference for the technical choice of automatic planning.

Conclusions
Dosimetric analysis of lung cancer and NPC in Tomo, Monaco, and Eclipse shows that the VMAT plan of the Monaco is the best therapeutic schedule for lung cancer. For advanced NPC, the HT plan is the best option.   DVHs of OARs for NPC

Supplementary Files
This is a list of supplementary les associated with this preprint. Click to download.