Dosimetric effect of different isocenter for nasopharyngeal carcinoma with volumetric modulated arc therapy

The purpose of this study was to analyze the dosimetric effect of different isocenters with volumetric modulated arc therapy for nasopharyngeal carcinoma (NPC).

S u m 1 4 1 0 5 2 0 0 2 0 the dosimetric advantage over intensity-modulated radiation therapy (IMRT), as well as its lower radiotherapy time (RT). [3][4][5][6][7][8] Because the current RT technology is mainly the isocentric irradiation technique, the position of the isocenter is very important. There are numerous literature reports regarding the dosimetric effects of errors of the isocenter on a variety of cancers with VMAT or IMRT. [9][10][11][12][13][14][15] To our knowledge, no data are available on the dosimetric impact of different isocenters for NPC patients regardless of VMAT or IMRT status. Therefore, the present study aimed to elucidate the dosimetric effects of different isocenters for NPC with VMAT.

Patients
A total of 20 non-metastatic NPC patients who had received VMAT treatment between April 2018 and July 2018 in Zhejiang Cancer Hospital were re-planned for our study. The study population included 15 men and five women, and the median age was 53 years (range 38-79 years). T1, T2, T3, and T4 had two, four, nine, and five patients, respectively, according to International Union Against Cancer 2010.
The data of the tumor stages are shown in Table 1. This study was approved by the institutional review board of Zhejiang Cancer Hospital, and all the patients provided voluntary informed consent to participate in the study.

Volume definition and dose prescription
As described previously, the gross tumor volume of the nasopharynx (GTV nx ) includes the primary tumor and metastatic retropharyngeal lymph nodes. 16 Metastatic cervical lymph nodes are defined as the gross tumor volume of the involved cervical lymph nodes (GTV nd ). The high-risk clinical target volume CTV 1 includes the GTV nx and GTV nd with a margin of 5-10 mm, entire nasopharynx, inferior two-thirds of the sphenoid sinus, anterior third of the clivus, pterygoid fossae, posterior third of the nasal cavity and maxillary sinuses, parapharyngeal space, retropharyngeal nodes, and drainage of the upper neck. The low-risk clinical target volume CTV 2 encompasses the CTV 1 with a margin of 3-5 mm, lower neck, and supraclavicular lymphatic drainage region. The planning target volume (PTV) is defined as the area 3-5 mm outside of CTV or GTV. The dose prescribed was as follows: 70 Gy to PGTV nx and PGTV nd , 60 Gy to PTV 1 , and 54 Gy to PTV 2 (The PGTV is defined as the area 3 mm outside of GTV. The PTV is defined as the area 3-5 mm outside of CTV. So PGTV nx is defined as the area 3 mm outside of GTV nx , PGTV nd is defined as the area 3 mm outside of GTV nd , PTV 1 is defined as the area 3-5 mm outside of CTV 1 , PTV 2 is defined as the area 3-5 mm outside of CTV 2 ). The total doses of PGTV nx , PGTV nd , PTV 1 , and PTV 2 were given in 33 fractions. All patients were irradiated with one fraction daily, 5 days per week. In the study, organs at risk (OARs) mainly included the brainstem, spinal cord, lenses, eyeballs, optic nerves, optic chiasm, temporal lobes, and parotid glands.

Choosing the isocenter position
We usually moved the isocenter to the geometric center of the target volume if the location position was not suitable for the plan. There were four target volumes for NPC patients. Of these, the highest dose targets were PGTV nx and PGTV nd , and the lowest dose target was PTV 2 . Thus, three isocenters were generated for each patient: the first using the geometric center of PGTV nx as the isocenter (AP), the second using the geometric center of PGTV nd as the isocenter (BP), and the third using the geometric center of PTV 2 as the isocenter (CP).
Therefore, each patient had three different VMAT plans with differ-

Planning design
A trilogy machine model was used in the study. We adopted RayArc of

Plan comparisons
The dosimetric comparison criteria of the plans are as follows:  AP-V, the first plan using the center of PGTV nx as the isocenter; BP-V, the second plan using the center of PGTV nd as the isocenter; CI-, conformity index of; CP-V, the third plan using the center of PTV 2 as the isocenter; HI-, homogeneity index of; The target PGTV nx , PGTV nd , PTV 1 , PTV 2 are defined in "2.2 Volume definition and dose prescription".

Statistical analysis
Results are described as the mean ± standard deviation. The twotailed Wilcoxon matched-pairs signed-rank sum test was carried out to analyze the difference between the three different isocenter plans in the CI and HI of the targets, D max , D mean , V 60Gy , and V 30Gy of the OARs; the NT absolute dose volumes of V 10Gy , V 20Gy , V 30Gy , V 40Gy , and V 50Gy ; and the MUs. A two-tailed P-value <0.05 is considered statistically significant. All analyses were carried out using the statistical software SPSS 19.0 (IBM Corporation, Armonk, NY, USA).

Target CI and HI
For a paired comparison, the CIs of PGTV nd and PTV 2 with BP-V and CP-V were found to be statistically significantly greater than that of AP-V. The HIs of PTV 2 with BP-V and CP-V were found to be statistically significantly smaller than that of AP-V. PGTV nx and PTV 1 were found to have no statistically significant differences with the three groups in the CI and HI (Table 3).  (Table 4).

NT dose volume and MUs
In the present study, we counted the absolute volume of NT with V 10Gy , V 20Gy , V 30Gy , V 40Gy , and V 50Gy . V 10Gy of AP-V was statistically significantly reduced by 3.7% with BP-V, and 3.0% with CP-V. V 20Gy of AP-V was statistically significantly reduced by 1.6% with BP-V, and 1.6% with CP-V. V 30Gy of AP-V was statistically significantly reduced by 1.4% with BP-V, and 1.9% with CP-V. However, V 50Gy of AP-V was statistically significantly increased by 1.4% with BP-V, and 1.9% with CP-V. V 10Gy , V 20Gy , V 30Gy , and V 50Gy were not statistically significantly different between BP-V and CP-V. V 40Gy was not statistically significant in the three groups. The MUs of AP-V were found to be statistically significantly reduced by 11.5% with BP-V, and 10.2% with CP-V (Table 5).

DISCUSSION
The treatment of NPC has included CRT, 3D-CRT, IMRT, and VMAT.
IMRT and VMAT are the main RT techniques for NPC patient treatment. For VMAT and IMRT, different settings in the plan design might cause dosimetry differences in the plans for a variety of cancers; these differences include the number of arcs, 6,20,21 the spacing units of the gantry for VMAT, 22 the angle of the collimator, 23 the calculation grid size, 24 and the photon energy. 25 The isocenter is very important, because RT usually uses an isocentric irradiation technique. The movement of the isocenter for the gamma knife is convenient, and more multi-isocenter irradiation technology is used. There are several studies regarding the dosimetric differences of different isocenters for the gamma knife. 26,27 In addition, TA B L E 4 Dosimetric comparison for organs at risk between the first plan using the center of PGTV nx as the isocenter, the second plan using the center of PGTV nd as the isocenter, and the third plan using the center of PTV 2 as the isocenter AP-V, the first plan using the center of PGTV nx as the isocenter; BP-V, the second plan using the center of PGTV nd as the isocenter; CP-V, the third plan using the center of PTV 2 as the isocenter; D max , maximum dose; D m , mean dose; L, left; R, right; V 60Gy (cc), absolute volume >60 Gy; V 30Gy (%), volume percentage >30 Gy. The target PGTV nx , PGTV nd , PTV 2 are defined in "2.2 Volume definition and dose prescription". AP-V, the first plan using the center of PGTV nx as the isocenter; BP-V, the second plan using the center of PGTV nd as the isocenter; CP-V, the third plan using the center of PTV 2 as the isocenter; MUs, monitor units; V 10Gy (cc), absolute volume >10 Gy; V 20Gy (cc), absolute volume >20 Gy; V 30Gy (cc), absolute volume >30 Gy; V 40Gy (cc), absolute volume >40 Gy; V 50Gy (cc), absolute volume >50 Gy.

P-value
there are reports of multi-isocenter technology of RT with a linear accelerator. 28,29 Linear accelerator RT currently uses the isocentric irradiation technique, which generally just has an isocenter for the treatment. In most hospitals globally, if multi-isocenter technology is used, the RT technician needs to enter the machine room to move the treatment bed. This is very inconvenient and increases the patient's irradiation time, which is not conducive to the stability of the patient's RT position.
Our comparative planning study first compared the dosimetric difference produced by different single isocenters for NPC with VMAT. In the present study, the AP-V showed its superiority in protecting the optic nerves, optic chiasm, and eyeballs compared with BP-V and CP-V. In the NT, AP-V also showed its superiority in V 10Gy , V 20Gy , and V 30Gy . The AP-V could also use fewer MUs to meet the clinical requirements. The first reason might be that the MLC of each control point would first open near the isocenter point when the treatment planning system received the VMAT plan.