A comprehensive and clinical‐oriented evaluation criteria based on DVH information and gamma passing rates analysis for IMRT plan 3D verification

Abstract Purpose To accomplish the 3D dose verification to IMRT plan by incorporating DVH information and gamma passing rates (GPs) (DVH_GPs) so as to better correlate the patient‐specific quality assurance (QA) results with clinically relevant metrics. Materials and methods DVH_GPs analysis was performed to specific structures of 51 intensity‐modulated radiotherapy (IMRT) treatment plans (17 plans each for oropharyngeal neoplasm, esophageal neoplasm, and cervical neoplasm) with Delta4 3D dose verification system. Based on the DVH action levels of 5% and GPs action levels of 90% (3%/2 mm), the evaluation results of DVH_GPs analysis were categorized into four regions as follows: the true positive (TP) (%DE> 5%, GPs < 90%), the false positive (FP) (%DE ≤ 5%, GPs < 90%), the false negative (FN) (%DE> 5%, GPs ≥ 90%), and the true negative (TN) (%DE ≤ 5%, GPs ≥ 90%). Considering the actual situation, the final patient‐specific QA determination was made based on the DVH_GPs evaluation results. In order to exclude the impact of Delta4 phantom on the DVH_GPs evaluation results, 5 cm phantom shift verification was carried out to structures with abnormal results (femoral heads, lung, heart). Results In DVH_GPs evaluation, 58 cases with FN, 5 cases with FP, and 2 cases with TP were observed. After the phantom shift verification, the extremely abnormal FN of both lung (%DE = 21.52%±8.20%) and heart (%DE = 19.76%) in the oropharyngeal neoplasm plans and of the bilateral formal heads (%DE = 26.41%±13.45%) in cervical neoplasm plans disappeared dramatically. DVH_GPs analysis was performed to all evaluation results in combination with clinical treatment criteria. Finally, only one TP case from the oropharyngeal neoplasm plans and one FN case from the esophageal neoplasm plans did not meet the treatment requirements, so they needed to be replanned. Conclusion The proposed DVH_GPs evaluation method first make up the deficiency of conventional gamma analysis regarding intensity information and space information. Moreover, it improves the correlation between the patient‐specific QA results and clinically relevant metrics. Finally, it can distinguish the TP, TN, FP, and FN in the evaluation results. They are affected by many factors such as the action levels of DVH and GPs, the feature of the specific structure, the QA device, etc. Therefore, medical physicist should make final patient‐specific QA decision not only by taking into account the information of DVH and GPs, but also the practical situation.

rics (such as the estimated deviations in dose volume histograms) 15 .
However, Nelms et al. 2 , M. Stasid et al. 16 , and Anna Fredh et al. 17 found that the dose deviation during clinical practice cannot be properly predicted by the GPs of whole body. According to Heming Zhen et al. 18 , though the distilled GPs of whole body was able to be used to quantitatively evaluate the quantity of dose deviations within the ROI, it cannot provide the intensity information of dose deviation and corresponding spatial information. The acceptance criteria of current patient-specific QA should be decided based on whether the DVH difference of the current plan meets the clinical treatment objective. M. Stasid et al. 16 , G. Heilemann et al. 19 , and Jinling Yi et al. 20 found that the GPs of individual volume were more sensitive to dose deviation, so they adopted the GPs of individual volume instead of that of whole body. That can solve the problem of weak correlation between the GPs evaluation result and the clinically relevant metrics to some extent, while removing the limitations to intensity information and spatial information of dose deviation in whole body gamma analysis. Subsequently, M. Cozzolino et al. 21 proved again that GPs had weak correlation with clinical dose deviation. At the same time, he also recommended that more reference should be made to DVH information in the patient-specific QA in addition to focusing on the GPs of specific structures. Ruurd Visser et al. 22 and A. Sdrolia et al. 23  In fact, Nelms et al. 2 had proposed the initial concept of achieving the division of evaluation results based on GPs action levels and DVH action levels in his study as early as in 2011. His basis was the "false negative" and "false positive" in 2D verification results of IMRT plans. Also, Ruurd Visser et al. 22 completed the 3D dose verification by the GI evaluation incorporating DVH information. That achieved the division in responsibility of the medical physicist and radiation oncologist within the QA procedure. From these studies, the introduction of the corresponding DVH information on the basis of the individual volume gamma analysis undoubtedly improved the correlation between the gamma analysis results and clinically relevant metrics. However, Nelms et al. 2 only proposed the division between "false negative" and "false positive" in 2D verification results in their study. They did not clarify the action levels of DVH information and GPs. In the study of Rusd Visserd et al. 22 , GPs were separated from DVH information, and the action levels of the DVH information were too strict. Therefore, this study aims to accomplish 3D dose verification by incorporating the GPs and DVH information.
Then, it proposes appropriate action levels to analyze the non-negative results in verification of IMRT plan, so that the patient-specific QA can be completed by properly combining the clinical relevant metrics.

2.A | QA plans
In this study, IMRT treatment plans for 51 patients were selected for dose verification. First, the dose of the 51 IMRT plans was calculated on a 2.5-mm isotropic dose grid with anisotropic analytical algorithm (AAA) through Eclipse v. 13.5 (Varian Medical Systems, Palo Alto, CA, USA). After that, these plans were delivered by a 6-MV linear accelerator (Unique, Varian Medical Systems, Palo Alto, CA, USA). The accelerator was equipped with the millennium 120 multileaf collimators. In the dose verification, the structures in all plans were categorized into target volume and organs-at-risk (OAR).The details were as shown in Table I. 2.B | QA procedure As shown in Figure 1, the QA procedure contained two parts. In the first part, all plans' isocenter was matched with Delta4 phantom's center. The RT plan and RT dose of these plans were calculated by TPS based on Delta4 phantom. Then the measured dose of these plans on the linear accelerator was acquired by Delta4 system. Finally, these plans were analyzed and compared through the ScandiDos Delta4 software in combination with RT dose, RT plan, and RT structure imported by TPS system. In that way, the DVH information and GPs of specific structures were obtained. As for the second part, the process was basically same except for two distinctions. First, dose verification was only performed to 17 cervical neoplasm plans. Second, when calculating the Delta4 phantom dose, the Delta4 was moved 5 cm to the right by facing Gantry based on the isocenter of the first part, so that the entire left femoral head was completely situated inside of the Delta4 phantom.
The shifting of Delta4 phantom was the most important distinction in the two parts.

2.C | Data analysis
With the help of ScandiDos Delta4, according to the imported RT structure, we obtained specific structures' GPs and corresponding DVH information based on the criteria of 3%/2 mm (global normalization). Of course, they were the data within the prescription dose coverage region ranging from 10% to 500%. According to Table I, the dose errors (%DE) between the predicted dose and measured dose of specific structures' DVH index were calculated as follows: where, %DE is the relative error between the planned dose and set the DVH action levels of 2%-5%, but they concluded that the action levels were too strict for some specific structures such as the target volume and OAR near the target volume. Yi et al. 20 and Jin et al. 24 attempted to adopt the DVH-based action levels of 3% and 5%, respectively, in the 3D gamma analysis. The ESTRO report 25 recommended an action limit of 5% for IC verification in the IMRT QA. Combined with the above study results, and considering the action limits in dose measurement recommended by AAPM TG-119 report and TG-218 report, the DVH action levels in this study was finally set to be 5%. Second, the universal action limits of GPs in gamma analysis were recommended to set to 90% (3%/2 mm and global normalization) in AAPM TG-218 report 14 . Therefore, the action levels of GPs in this study were also set to 90%.
As described in Figure 2, the action levels of the vertical axis %

3.A.3 | Evaluation results of cervical neoplasm plans
According to DVH_GPs of cervical neoplasm as shown in Figure 3(e) and 3(f), TN results were observed in PTV, rectum, and bladder.
There were 33 cases with FN results in femoral heads.
The %DE Dmean of left and right femoral heads were as high as 16.60%±7.69%, 36.21%±10.48%, respectively, and that severely exceeded the required DVH dose tolerance. Therefore, the evaluation results of femoral heads of these plans were unacceptable for clinical treatment, and they also required further analysis.

3.B | QA results after shifting of Delta4 phantom
In DVH_GPs evaluation, the %DE Dmean of the lung and heart in the esophageal neoplasm plans and of the femoral heads in cervical neoplasm plans were severely deviated from the normal value. The relevant parameters of these specific structures shown in Table III  as an example, Delta4 phantom was shifted 5cm horizontally to the right by facing gantry, so that the left femoral head was completely covered inside the phantom (as shown in Figure 4). Then, these plans were reverified and the DVH_GPs evaluation was re-executed.
To confirm whether V used /V tot had an impact on %DE Dmean and GPs, V used /V tot , %DE and GPs before and after the shifting were collected. Then, the two-tailed paired-sample T tests were carried out to the two sets of data, and a significant difference was found when  26,27 . That is why gamma analysis' capability in detecting clinically significant deviations has been questioned widely.
As presented in Figure 3 and Table II

| CONCLUSIONS
By adopting the individual volume gamma analysis, the DVH_GPs evaluation method is able to make up the disadvantage of lacking the dose intensity information and position information of the conventional simplex GPs evaluation. The DVH information is directly related to clinical treatment; hence it enhances the correlation between the results of Patient QA and the clinically relevant metrics.
In our study, by setting 5% DVH action levels and 90% GPs action levels for DVH_GPs analysis, we were able to further reveal the TP,

ACKNOWLEDG MENTS
The study was partially supported by a grant from the Chongqing Municipal Human Resources and Social Security Bureau (cx2018147), Key project from Chongqing Yuzhong District Science and Technology Commission (20190101).

CONFLI CT OF INTERESTS
The authors declare no conflict of interest.