Summary

METHODS
VMAT, IMRT, and HYBRID plans were generated for ten pediatric patients. In VMAT plans, triple arcs were utilized for cranial fields. Two full arcs were employed with avoidance sectors for each isocenter of spine fields. In IMRT plans, two opposing lateral fields in the brain and a single posterior field for each isocenter in the spinal region were used. This study obtained HYBRID plans by summing VMAT and IMRT plan. Plans were compared regarding homogeneity, conformity, and organs at risk doses.

RESULTS
The VMAT plan exhibited a significantly better conformity index than IMRT and HYBRID. The lowest V2 and V5 for body-PTV were obtained in IMRT plans. Compared with IMRT and HYBRID, V10 and V20 of lung, V25 of heart, and Dmean of left eye, thyroid, heart, esophagus, bowel, and liver were lower in VMAT plans.

CONCLUSION
The HYBRID was superior in terms of PTV dose coverage and homogeneity, and the best protection for many organs was provided in VMAT for CSI.

Introduction

Conventionally, the technique used for delivering CSI is three-dimensional conformal radiotherapy (3D-CRT). In this approach, two lateral opposed fields for the brain and one or more direct posterior fields for the spine, depending on the length of the spine, are utilized. To avoid high dose inhomogeneity that may occur at the field junctions in the plans created with 3D-CRT skin gap method is used, or the beam divergences of the fields are adjusted by rotating the couch and collimator.[2-4] In these methods, field matching is very sensitive to small setup uncertainties, which could result in very high or low dose regions in the field junctions.

The prone technique, as the setup positioning, is usually used in 3D-CRT. This position provides the visualization of the field junction regions on the patient's skin directly. However, most pediatric patients need anesthesia; the prone position limits the ability to see the airway and oral cavity. Numerous series have demonstrated that it is possible to deliver CSI while patients are in a supine position.[3,5,6]

Although the usage of one posterior field for the spine in 3D-CRT is advantageous for protecting the kidneys and lungs, the exit dose of this field passes directly through the organs anterior to the vertebrae, causing toxicities, including primary hypothyroidism and cardiovascular disease. Sophisticated approaches, such as volumetric modulated arc therapy (VMAT) and intensity modulated radiation therapy (IMRT), decrease exposure to organs at risk (OAR) and enhance dose conformity and homogeneity. These planning strategies show promise in the management of CSI. Most researchers have examined the VMAT-based CSI technique's various features following its initial description by Fogliata et al.[7] in 2011, and it is now widely used in clinical applications. According to these studies, compared to 3D-CRT, VMAT treatments increase the low doses received by the whole body while decreasing the mean doses to organs, including the heart, thyroid, and parotid glands.[8-10] Sarkar et al.[11] indicated that a reduced dose to the body is obtained when a partial arc is used for the spine rather than a full arc. Furthermore, junction shifts are not required since it uses an overlapped fluence pattern and feathering algorithm to handle dose matching at the junctions in VMAT.[12]

By combining the two planning concepts into a hybrid method that minimizes the drawbacks of each method while maximizing its benefits, improved dose distribution and better organ sparing may be achieved. Many studies show the advantages of hybrid planning in nasopharynx, breast, and lung radiotherapy.[13-15] A recent study emphasized that the doses received by critical organs, such as the heart, kidney, lung, and lens, were lower in novel hybrid plans prepared with C-arm linac for one pediatric CSI patient compared to 3D-CRT and VMAT.[16] Although VMAT-based craniospinal irradiation using the Halcyon system has been previously reported, comparative evaluations including IMRT and HYBRID techniques within the same patient cohort remain limited. This study aimed to investigate the dosimetric evaluation of IMRT, VMAT, and HYBRID plans created for CSI with Halcyon linac.

Methods

Simulation and Contouring
All patients were immobilized in the head-first supine position, which enables airway access for anesthesia, using a thermoplastic fixation head mask and a vacuum mattress. Computed tomography (CT) images of patients were acquired using Philips Big Bore CT (Philips Medical Systems, Highland Heights, OH, USA) with a 3 mm slice thickness. The whole brain clinical target volume (CTV_brain) was contoured such that the inferior border was at least 0.5 cm below the foramen magnum skull base and included the frontal lobe, cribriform plate region, and superior orbital fissure. PTV_brain was created by adding a 3 mm setup margin.[17] The whole spine CTV_spinal was contoured to include the entire thecal sac and extend to the subarachnoid space along the intervertebral foramina and nerve roots. A minimum of 1 cm margin was given to cover the recesses of all vertebral bodies on both sides. The lower border was evaluated with the spinal MRI. The lower border is 2 cm below the end of the subdural space and extends to the S2-S3 interval. PTV_spinal was created by adding a 5 mm setup margin.[17] The PTV margins were defined separately due to regional differences in setup uncertainties. A 3 mm PTV margin was used for the cranial region because of more rigid immobilization and higher setup accuracy. In contrast, a 5 mm PTV margin was applied for the spinal region due to the longer treatment field, increased geometric variability associated with patient positioning, and greater setup uncertainty. The final PTV was created by summing PTV_brain and PTV_spinal. The delineated various OARs, including the brainstem, optic chiasm, optic nerves, eyes, lenses, parotids, thyroid, larynx, heart, esophagus, bowel, liver, stomach, kidneys, and lungs. To assess the dose to non-target tissue, the structure named body-PTV was generated by excluding the PTV from the whole-body contour.

Treatment Planning
VMAT, IMRT, and HYBRID plans were generated for each patient with 6 MV FFF photon beams from Halcyon linac in the Eclipse v17.01 (Varian, Palo Alto, CA) treatment planning system (TPS) by the same medical physicist. Halcyon has stacked and staggered dual-layer multileaf collimators (MLC). This MLC configuration offers an advantage in terms of minimizing leaf transmission. The maximum speed of the leaves is 5 cm/s, which is two times faster than Millennium 120-leaf MLC. The dose rate was 800 MU/min. The photon optimizer was used for plan optimization, and final dose calculations were performed using the anisotropic analytical algorithm (AAA), which is the clinically validated and routinely used algorithm in our institution. The calculation grid size was selected as 2.5 mm. The total dose of 36 Gy in 20 fractions was prescribed for PTV.

In VMAT plans, triple coplanar arcs, each with a length of 358° arc, were utilized for cranial fields. The arcs were set at 181° to 179° (clockwise), 179° to 181° (counter-clockwise), and 181° to 179° (clockwise) with collimator angles of 30°, 330°, and 90°, respectively. Two full coplanar arcs were employed with avoidance sectors of 250°-110° in the clockwise direction, and 110°-250° in the counter-clockwise direction for each isocenter of the spine fields since the study emphasized that the 140° posterior arc length is sufficient for spine PTV.[18] Furthermore, using a partial arc instead of full arc for spine fields offers the advantage of reducing the low doses received by the body.[11] The collimator angles of the arcs were defined as 5° and 355° for spine fields. The number and positioning of isocenters were determined to create an overlapping length of approximately 10 cm between adjacent fields. In all plans, three isocenters were used because the PTV length ranged from 50.2 cm to 59.1 cm. The first isocenter was placed in the brain, and the second and third were in the superior and inferior spine, respectively. There was just a longitudinal axis difference between the isocenters due to their placement. A sample for the placement of isocenters and arc arrangement is shown in Figure 1. All arcs were optimized together at the same time. To improve dose homogeneity inside the field junction, a TPS-integrated automatic feathering (AF) algorithm was utilized during plan optimization. Furthermore, a manual normal tissue objective (NTO) was employed to manage dose fall-off outside the PTV borders, considering the following parameters: Distance from the target border 0.3 cm, start/end doses 105%/60%, and fall-off 1. To prevent hotspots from forming outside of the PTV, a shell structure with a 3 mm separation from the PTV was used. Priorities of shell and NTO, similar to those of OARs, were set at 150 while the PTV was 200. The optimization was done until the dose to the OARs was as low as possible without compromising the target coverage.

Fig 1: The arc arrangement (a) and placement of isocenters (b).

In IMRT plans, an attempt was made to obtain a dose distribution similar to the 3D-CRT technique by using two opposing lateral fields in the brain and a single posterior field for each isocenter in the spinal region, as in the 3DCRT technique. The collimator angle of all fields was set as 0°. The isocenters placement and optimization approach were the same as those of the VMAT plans. The IMRT plans were generated using inverse planning in the treatment planning system. The automatic (NTO) was utilized to manage dose fall-off outside the PTV borders. No shell structure was used. The hot spots were delineated as avoidance structures for subsequent optimizations to diminish them. Additionally, these spots were avoided by using fluence editing. The planner can adjust the fluence distribution of a field in beams eye view (BEV) using the fluence editor. Thanks to this editor, hot spots can be reduced.

In this study, HYBRID plans were generated by independently optimizing VMAT and IMRT plans within the treatment planning system. The total prescribed dose was equally divided between VMAT and IMRT. A dose of 18 Gy in 10 fractions was assigned to each technique, and their sum represented the HYBRID plan.

The plan acceptance criteria for all plans were that at least 95% of PTV received 95% of the prescription dose (D95% ≥ 95% of the prescribed dose), and the doses to OARs were met according to the QUANTEC table of dose limits.[19] The mean dose (Dmean) to the lungs, kidneys, heart, and lens should be below 7 Gy, 15 Gy, 26 Gy, and 7 Gy respectively; the heart volume receiving 25 Gy (V25) should not exceed 10%.

Dosimetric Evaluation
All data from 30 treatment plans were collected via dose volume histograms (DVHs) calculated using TPS. VMAT, IMRT, and HYBRID plans were evaluated regarding target coverage, dose homogeneity, conformity, and OAR doses. The following formulas were used to calculate the conformity index (CI) and homogeneity index (HI).[20,21] The ideal value of the CI is 1.

Fig 7: Conformity index (CI) and homogeneity index (HI) calculation formulas.

In the CI formula, TVRI means the volume covered by reference isodose, TV means the target volume, and VRI means the volume of reference isodose. In the HI formula, Dx% means the dose received by x% volumes of the PTV. A HI value of 0 means that the dose distribution is homogeneous.

Doses of 95% (D95%, target coverage), 98% (D98%, significant minimum), 2% (D2%, significant maximum), Dmean, and volume receiving 107% of the prescribed dose (V107%) of PTV were assessed. The percentage volume receiving at least 2, 5, 10, 15, 20, 25, 30, 34.2, and 36 Gy (V2, V5, V10, V15, V20, V25, V30, V34.2, and V36) of body-PTV was analyzed. A dose of 1 cc (D1cc) and the Dmean were examined for OARs. The percent lung volumes receiving 5, 10, and 20 Gy (V5, V10, and V20) were also compared. Additionally, the total monitor units (MU) for all three techniques were recorded and analyzed.

IBM SPSS software package version 20.0 was used to conduct statistical analysis of the collected data. The analyses were carried out using the non-parametric Wilcoxon signed-rank test due to the limited sample size. A level of P values below 0.05 were considered statistically significant.

Results

Table 1: Dosimetric parameters of PTV and doses for BODY-PTV

Fig 2: The dose distribution of (a) VMAT, (b) IMRT, and (c) HYBRID. The dose color wash legend displays a dose from 50% of the prescribed dose to the plan's maximum value.

Non-Target Tissue (Body-PTV)
The lowest V2 and V5 for body-PTV were obtained with IMRT (p1<0.01 for VMAT vs. IMRT, p3<0.01 for IMRT vs. HYBRID), followed by HYBRID and VMAT plans. There was no significant difference between IMRT and VMAT plans in body-PTV V10. This value was significantly higher in HYBRID plans than in IMRT and VMAT. The other dosimetric parameters calculated in the current study for body-PTV were significantly lower in VMAT plans compared to IMRT and HYBRID. The graphical representation of the doses received by the body-PTV is shown in Figure 3.

Fig 3: Doses received by body-PTV for each plan.

OARs
Table 2 and Figure 4 exhibit a comparison of the mean doses to the OARs for each plan. The mean dose constraints for the heart, lungs, and kidneys were achieved across all three techniques; however, the lens dose constraint was not met in any of the evaluated plans. The ALARA (As Low As Reasonably Achievable) principle was considered for the lens, and efforts were made to minimize the dose as much as possible despite anatomical and planning limitations. Figure 5 shows the lung V5, V10, and V20 for each plan. The Dmean of the lenses and kidneys and the V5 of the lung in IMRT plans were significantly lower than those in VMAT and HYBRID plans. HYBRID plans showed significantly better sparing than VMAT plans in terms of the Dmean of the lenses and kidneys and V5 of the lung. No significant dose difference in the Dmean of the right eye, parotids, larynx, stomach, and lung was observed among the three radiotherapy plans. In comparison with IMRT and HYBRID, the V10 and V20 of the lung, V25 of the heart, and the Dmean of the left eye, thyroid, heart, esophagus, bowel, and liver in the VMAT plans were significantly reduced. Additionally, there was a significant reduction of these OAR doses with HYBRID plans compared to the IMRT plan.

Table 2: Dmean for the OARs of each plan

Fig 4: Dmean of the OARs of each plan.

Fig 5: The lung V5, V10, and V20 for each plan.

Figure 6 demonstrates the D1cc of the OARs for each plan. The lowest D1cc of the right eye, the left optic nerve, parotid, thyroid, heart, lung, esophagus, liver, stomach, and left kidney were obtained with VMAT, followed by HYBRID and IMRT. The IMRT plans were superior regarding the D1cc of the lens and brainstem than HYBRID and VMAT. The D1cc of the left eye and right kidney were minimized in HYBRID plans compared to VMAT and IMRT. In the pairwise comparison for planning techniques, the differences were statistically significant. There were no significant dose differences among the three radiotherapy plans in terms of the D1cc of the right optic nerve, optic chiasma, larynx, and bowel.

Fig 6: D1cc for the OARs of each plan.

Monitor Units
The MU values are presented as median (range) as follows: 1031.7 (1003.1-1086.3) for ARC, 1429.6 (1336.9-1562.5) for IMRT, and 1242.4 (1173.4-1304.5) for HYBRID. IMRT plans exhibited the highest MU values, whereas VMAT plans had the lowest. The MU values of hybrid plans were significantly higher than those of VMAT plans but significantly lower than those of IMRT plans (all comparisons, p<0.01).

Discussion

In the present study, the homogeneity and target coverage improved with HYBRID plans compared to other strategies. The best conformality was obtained with VMAT plans. However, the greatest V107% value and the worst dose homogeneity for PTV were with VMAT plans. The use of a partial arc instead of a full arc in spine fields and employing stricter manual NTO values in optimization to reduce the low dose spillage may account for these results. Since the fields in IMRT were designed following the 3D-CRT approach, the worst CI values were acquired with IMRT plans. The conformity similar to VMAT plans could be achieved by increasing the number of fields in IMRT plans. The body-PTV volumes exposed to low doses, such as 2 and 5 Gy, were the highest in VMAT plans, and it has been observed that these values could be reduced with the HYBRID technique. On the other hand, the lowest volumes of body-PTV receiving doses of 10 Gy and above were obtained in VMAT plans. The best OAR protection was achieved with VMAT plans, except for lenses, kidneys, and lung V5.

Many studies indicated that the HYBRID planning technique improves dose homogeneity compared to VMAT and IMRT in different anatomic regions, such as nasopharyngeal carcinoma, cervical cancer, and left-sided breast cancer.[13,24-27] Our result was consistent with these studies.

Luo et al.[28] developed a novel hybrid technique for CSI and compared it with 3D-CRT regarding conformality and OAR doses for four patients. In their HYBRID technique, the same cranial fields as in the 3D-CRT approach were used, and only static spine fields were changed with the rapid arcs. They indicated that the Dmean of the heart and esophagus and lung V20 were decreased while the Dmean to lungs and kidneys and lungs V5 were increased in the hybrid technique. In our study, we described the HYBRID plan with a different approach, but the spine fields utilized in their HYBRID technique are similar to arcs used in our VMAT plans. Also, in our IMRT plans, we used the 3D-CRT field principle. As a result, the comparison findings of VMAT and IMRT plans in our research were compatible with this study.

Ziemann et al.[16] performed a comparative evaluation between 3D-CRT, IMRT, VMAT, HYBRID treatment planning (HybTP), and helical tomotherapy (HT) in a 6-year-old pediatric patient with medulloblastoma. All plans were generated using 6 MV photon beams from a CLINAC 2100 DHX (Varian Medical Systems, Palo Alto, CA) equipped with a Millennium 120 MLC, with a prescription dose of 35.2 Gy in 22 fractions. In their hybrid approach, 3D-CRT fields were used except for the cardiac region, which was planned with VMAT. They reported CI values of 0.96, 0.86, and 0.83 and HI values of 0.14, 0.15, and 0.13 for VMAT, HybTP, and 3D-CRT, respectively. In our study, the mean CI values were 0.892±0.013, 0.875±0.015, and 0.764±0.027, and HI values were 0.109±0.007, 0.078±0.004, and 0.094±0.004 for VMAT, HYBRID, and IMRT, respectively. The CI of our HYBRID plans was comparable to their HybTP results; however, a more homogeneous dose distribution was achieved in our HYBRID plans. These differences may be attributed to variations in hybrid planning design and implementation strategies between the two studies. Regarding organ-at-risk doses, Ziemann et al. reported higher lung doses for VMAT and IMRT compared with QUANTEC criteria, which they attributed to the absence of partial arcs in VMAT and the use of multiple spinal fields in IMRT. In contrast, the mean lung dose in our study was approximately 7 Gy across all techniques, meeting QUANTEC constraints with minimal variation. This difference may be related to variations in beam arrangement and optimization strategies between the two studies. For low-dose bath, Ziemann et al.[16] reported body V5 values of 40%, 73%, 43%, and 55% for 3D-CRT, VMAT, HybTP, and HT, respectively, without specifying whether PTV subtraction was performed. In our study, body-PTV V5 values were 41.3±3.8%, 26.9±2.4%, and 34.4±3.1% for VMAT, IMRT, and HYBRID, respectively. Overall, both studies demonstrate that techniques incorporating 3D-CRT fields result in lower low-dose exposure, followed by hybrid approaches. Differences in study design (single-patient versus cohort-based evaluation) and hybrid implementation strategy (field arrangement and optimization approach) may account for the observed discrepancies.

Jakacki et al.[29] demonstrated that cardiac toxicity after CSI applications for pediatric patients is developed due to the single posteriorly directed beam. In a review by Ratosa et al.[30] it is underlined that after mediastinal irradiation, there is a linear radiation dose-response relationship between the mean absorbed dose to the heart (heart-Dmean) and the risk of cardiac mortality. Ziemann et al.[16] found that the lowest Dmean of the heart was in HT. However, the other studies present that VMAT was superior in terms of the Dmean of the heart compared to HT.[7,8] The Dmean of heart was around 9 Gy in VMAT plans in the literature.[16,31] In our study, the best heart protection was achieved in VMAT plans, in which the Dmean of the heart was 9.9 Gy. Our results agree with these studies.

The QUANTEC table points out that with V25>10%, the probability of long-term cardiac death is more than 1%. The heart V25 was 43.9, 0, and 9.8 for 3D-CRT, VMAT, and HybTP, respectively, in the investigation by Ziemann et al.[16] We found similar results for IMRT (created with 3D-CRT fields) and VMAT. In contrast to their study, the mean of heart V25 was 0.68±0.69 for HYBRID plans in our analysis. Using 3D-CRT fields is not an appropriate approach for protecting the heart.

Mayo et al.[15] reported that the Hybrid planning technique, a combination of static and IMRT beams, demonstrated advantages for reducing lung V5 compared to 4/5 of 9 fields IMRT in cancers of the lung and esophagus. Another study by Zhao et al.[32] also found that compared with VMAT, a Hybrid IMRT/VMAT technique significantly reduced lung V5 for non-small cell lung cancer. In our study, HYBRID plans are superior regarding lung V5 compared to VMAT.

There are a limited number of dosimetric studies regarding the CSI with Halcyon. Matsumoto et al.[33] performed CSI-VMAT planning for a 20-year-old male patient with leukemia in Halcyon. They reported that Halcyon VMAT accomplished a homogeneous and highly conformal dose distribution while sparing normal tissues and reducing treatment time. Furthermore, it is stated that auto-feathering optimization was efficient in minimizing uncertainties due to mechanical inaccuracies and patient setup errors.

Sarkar et al.[18] carried out a comparative dosimetric analysis of VMAT-based CSI plans for 25 adults and pediatric patients using the Halcyon and TrueBeam linear accelerators (linac). The study concluded that Halcyon-based VMAT CSI plans were dosimetrically superior with regard to OAR doses and provided lower spillage doses than TrueBeam plans.

Stroubinis et al.[34] performed a dosimetric comparison between Halcyon and Truebeam Edge linacs for two adult CSI patients. They found no differences in terms of doses to OARs and PTV coverage between Halcyon and Truebeam Edge. In addition, the study emphasized that Halcyon has an advantage in terms of treatment time compared to Edge. Biswal et al.[35] compared CSI plans for Halcyon and C-arm Novalis Tx linacs for 15 adult and pediatric patients. They reported that Halcyon was superior in terms of low-dose spillage and treatment time. None or minimal differences in the dose distribution were observed between Halcyon and Novalis Tx linacs.

Conclusion

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