Examination of the best head tilt angle to reduce the parotid gland dose maintaining a safe level of lens dose in whole‐brain radiotherapy using the four‐field box technique

Abstract The parotid gland is recognized as a major‐risk organ in whole‐brain irradiation; however, the beam delivery from the left and right sides cannot reduce the parotid gland dose. The four‐field box technique using a head‐tilting device has been reported to reduce the parotid gland dose by excluding it from the radiation field. This study aimed to determine the appropriate head tilt angle to reduce the parotid gland dose in the four‐field box technique. The bilateral, anterior, and posterior beams were set for each of ten patients. The orbitomeatal plane angle (OMPA) was introduced as an indicator that expresses the head tilt angle. Next, principal component analysis (PCA) was performed to understand the interrelationship between variables (dosimetric parameters of the lens and parotid gland and OMPA). In PCA, the angle between the OMPA vector and maximum lens dose or mean parotid gland dose vector was approximately opposite or close, indicating a negative or positive correlation [r = −0.627 (p < 0.05) or 0.475 (p < 0.05), respectively]. The OMPA that reduced the maximum lens dose to <10 Gy with a 95% confidence interval was approximately 14°. If the lens dose was not considered, the parotid gland dose could be reduced by decreasing the OMPA.

doses of >20 Gy or >25 Gy, respectively. 5 This result indicated that some patients exceeded dose tolerances of the parotid glands, based on the report by Deasy et al. that tolerances of one parotid gland and both glands that effectively prevent severe xerostomia were the mean doses of 20 and 25 Gy, respectively. 13 The standard prescription of PCI for LD-SCLC is 25 Gy in 10 fractions, 14 which is smaller than that for palliative cases (e.g., 30 Gy in 10 fractions). The risk of severe xerostomia may be relatively lower in patients who underwent PCI than in those who underwent palliative treatment; however, a lower mean dose to the parotid gland results in better function. 13 Several researchers have suggested techniques to reduce the dose entering the parotid gland. 8,11,12 Intensity-modulated radiotherapy is one of the useful techniques; however, it is time-consuming and costly. Regarding conventional techniques, Cho et al. reduced the parotid gland dose by cutting the radiation field at the patient's foot side 8 ; however, this technique is not suitable for patients with combined upper cervical spinal metastasis or leptomeningeal seeding.
Using another technique, Park et al. reduced the parotid gland dose with a noncoplanar beam 11 ; however, the technique is time-consuming because of the couch rotation in the treatment room. Instead of using these techniques, they proposed a new technique that spared the parotid gland from radiation fields in the four-field box irradiation using a head-tilting device. 12 This technique can be performed on patients with combined upper cervical spinal metastasis or leptomeningeal seeding and can be employed in many facilities because it is a simple four-field box irradiation without noncoplanar beams.
Therefore, this study aimed to determine the best head tilt angle to reduce the parotid gland dose in the four-field box technique. The optimal head tilt angle should be determined to reduce the parotid gland dose while maintaining a safe level of lens dose. The risk of cataract progression is known to be dependent on the radiation dose. In the study by Merriam et al., it was reported that the risk of cataract progression after an irradiation of 2.5-6.5 Gy and 6.51-11.5 Gy is 33% (latency: 8 yr) and 66% (latency: 4 yr), respectively. 15 Emami et al. estimated that the doses associated with the incidence of 5% and 10% of cataracts in 5 yr were 10-and 18-Gy, respectively. 16 Regarding the clinical goal of the lens dose in the treatment plan, Piroth et al. 17 and Yamazaki et al. 18 set 5 and 10 Gy at the maximum dose, respectively. These clinical goals were introduced as the dose constraint of the lens in accordance with a radiation oncologist's guide. 19 The four-field box technique would be more practical after determining the optimal head tilt angle to reduce the parotid gland dose and maintain a safe level of lens dose.

2.A | Patient selection and imaging
Ten patients who had previously undergone WB irradiation were selected and immobilized from the top of the head to the chin with a thermoplastic mask without using a head-tilting device, and 3-mm slice-thick computed tomography (CT) images (Aquilion LB, Cannon Medical Systems Co.) were acquired. In this study, instead of using a head-tilting device, an approach that simulated the head tilt by a treatment planning system was adapted. This study was approved by our institutional review board (No. 2020-1-021).

2.B | Contouring and treatment planning
The CT images were imported into a treatment planning system (RayStation, version 6.2.0, RaySearch Laboratories) for delineation of the target and high-risk organ volumes. The WB was delineated as a clinical target volume (CTV). A planning target volume (PTV) was created by adding 5-mm isotropic margins for the CTV. The parotid gland and lens were delineated as high-risk organs.
First, conventional bilateral beams were set up so that the beamline of the anterior side was parallel to the line connecting the left and right eye sockets. Additionally, a beam from the anterior direction was added with the couch angle of 90°. The beam from the anterior direction was set at a gantry angle where the lens was not included in the irradiation field and the beam from the posterior direction was set on the opposite side. The four-field box plan based on this procedure was defined as the "original plan." Next, two new plans were created by tilting AE5°of the beam angle from the anterior and posterior directions of the original plan. For example, if beam angles from the anterior and posterior directions in the original plan were 30°and 210°, respectively: one was 35°and 205°and the other was 25°and 215° (Fig. 1). The remaining beams were unchanged.
Regarding three plans for each patient, collimator angles of 90°a nd 0°were adapted for the bilateral and remaining beams, respectively. Although a leaf margin of ≥5 mm was basically added to the PTV, the multi-leaf collimator was closed up to the position where it did not interfere the PTV in order to reduce the lens dose. Figure 2 shows representative radiation fields of the fourfield box technique.
The beam weight from each direction was equal, and no physical or virtual wedges were used. The energy of all beams was 10 MV of TrueBeam (Varian Medical Systems, Inc.). The PCI was assumed; therefore, a dose prescription of 25 Gy in ten fractions was used.
The prescription to the reference point generally adopted in the WB irradiation greatly varies in dose distribution depending on the position. In this study, a volume prescription (prescription to 95% of the PTV: D 95% ) that facilitates easy planning comparison was adopted.

2.C | Calculation of the head tilt angle and dosimetric parameters
The head-tilting device was not used in the treatment planning CT, and the head tilt angle was set by measuring the gantry angle with the couch angle of 90°. For example, (a) the gantry angle of α°without the tilting device is equivalent to (b) the gantry angle of 0°with the tilting device of α°as shown in Fig. 3. The virtual orbitomeatal plane angle (OMPA virtual ) was introduced as an indicator that expresses the head tilt angle. It was defined by subtracting the actual OMPA in the direction perpendicular to the couch from the anterior gantry angle (A gantry ): The OMPA virtual value increases when the patient's jaw is pulled.
Since the OMPA can be measure from outside the patient body without using CT images, by tilting the head for the calculated OMPA virtual in the treatment planning CT phase, the above-described treatment plan can be designed without rotating the couch.
To determine the best OMPA virtual to reduce the parotid gland dose in a clinically usable treatment plan, the following parameters were calculated: the dose to 98% of the PTV (D 98% ), maximum dose, homogeneity index (HI) 20 and conformity index (CI) 20

2.F | Statistical analysis
The correlation between dosimetric parameters and OMPA virtual in the four-field box plan was analyzed using the Spearman's rank correlation.

3.A | The interrelationship between dosimetric parameters and OMPA virtual in the four-field box plan
In PCA, proportions of the PC1 and PC2 variance were 41% and 33%, respectively. The cumulative proportion was 74%. Figure 4 shows the biplot, where each data point corresponds to a treat-    3.C | Calculation of normal tissue complication probability for parotid gland toxicity

| CONCLUSION
This study examined the best head tilt angle to reduce the parotid gland dose in WB radiotherapy using a four-field box technique. Since the parotid gland dose is inversely related to the lens dose, the orbitomeatal plane angle required to reduce the maximum lens dose to ≤10 Gy and minimize the parotid gland dose was 14°. If the lens dose was not considered, the parotid gland dose could be reduced by decreasing the orbitomeatal plane angle.

ACKNOWLEDGMENTS
We are grateful to Mr.

APPEN DIX A
HI and CI values were calculated as follows: In Eq. (A1), D 2% , D 98% and D 50% indicated the doses of 2%, 98% and 50% of the target volume, respectively. In Eq. (A2), TV was the target volume, TV RI was the target volume covered by the reference isodose line, and V RI was the volume inside the reference isodose line. In this study, the reference isodose was 25 Gy.

APPENDIX B
Normal tissue complication probability (NTCP) was calculated using the following equation: and