Research ArticleClinical Studies
Open Access

Treatment Planning Comparison of Gantry-based and Fixed Beams for the Treatment of Liver Tumors With Carbon Ion Therapy

YUYA MIYASAKA, SUNG HYUN LEE, HIKARU SOUDA, TAKASHI KANEKO, YASUHITO HAGIWARA, HONGBO CHAI, MIYU ISHIZAWA, HIRAKU SATO and TAKEO IWAI
In Vivo November 2024, 38 (6) 3002-3010; DOI: https://doi.org/10.21873/invivo.13783

Abstract

Background/Aim: This study aimed to compare the use of a rotating gantry in liver tumor carbon-ion radiotherapy using of a fixed-port for treatment planning. Materials and Methods: Thirty patients with liver tumors were analyzed. Three treatment plans were developed for each case: one with a rotating gantry with a 360° angle, one with fixed ports of 0° and 90° with a ±20° couch rolling setting, and one with fixed ports of 45° and 90° with a ±20° couch rolling setting. The dose–volume histogram parameters of the clinical target volume (CTV) and organs at risk (OARs) for each treatment plan were compared. Results: Significant differences in the volume of the liver-gross tumor volume (GTV) of normal liver irradiated with 5 Gy to 15 Gy were found between the gantry treatment plans and fixed-port treatment plans. There were no significant differences in the OARs, except for the CTV and liver GTV, between the gantry and fixed-port treatment plans. Conclusion: The study results support the potential of using a rotating gantry to reduce liver doses, especially in the low-to-medium dose range, while maintaining target and OAR doses except for the liver. A rotating gantry could be especially useful in cases in which the relationship between the tumor and OAR is complicated by location.

Key Words:

Carbon-ion radiotherapy (CIRT) for various tumor sites has demonstrated reasonable outcomes (1-6). The advantages of CIRT over X-ray and proton therapy include an optimal dose distribution due to the Bragg peak and small penumbra as well as high biological efficacy (7-9). The number of facilities using CIRT is much smaller than those using X-ray or proton therapy despite this effectiveness (10). This difference is caused by the cost of building facilities for CIRT equipment, which is much higher than that of X-ray or proton therapy equipment (11). Additionally, the enormous size of the synchrotron has made device development difficult, and developing rotating gantry in CIRT lagged far behind compared to the development of other modalities. Therefore, from the 1990s to the early 2010s, treatment in fixed-port treatment rooms was the norm (12-15). Recently, a compact rotating gantry for CIRT using superconducting technology was developed and is now commercially available for clinical use (16-18). The CIRT rotating gantry system allows setting beam angles that are difficult to set in a fixed-port treatment room. However, the mechanism of treatment planning improvement for many other tumor sites by beam angle setting using a rotating gantry remains unclear.

Clinical studies for tumors located within the liver treated with CIRT have shown promising results (19-25). Sparing as much of the normal liver as possible while delivering a sufficient dose to the tumor and reducing the dose to the surrounding gastrointestinal tract, kidney, and spinal cord is important for treating liver tumors.

Thus, this study aimed to evaluate the effect of the freedom to set the rotating gantry beam angle on treatment planning for CIRT of liver tumors.

Patients and Methods

Patient selection and image acquisition. The Institutional Review Board of our institution approved this single-center retrospective study. This study analyzed 30 consecutive patients with liver tumors who underwent CIRT from September 2022 to March 2023 (Table I). All included cases were treated with the CIRT rotating gantry. An Aquilion ONE (Canon Medical Systems, Otawara, Japan) was used as the computed tomography (CT) scanner for treatment planning. The patient was positioned supine or prone with arms raised, and a BlueBAG (Elekta AB, Stochholm, Sweden) and a Hipfix thermoplastic positioner (CIVCO Medical Solutions, Kalona, IA, USA) were used to immobilize the patient. Four-dimensional CT (4DCT) images corresponding to respiratory motion were acquired with the treatment couch rolling set to 0°. An AZ-733VI (ANZAI Medical, Tokyo, Japan) was used to obtain respiratory waveforms from abdominal wall displacement. The most expiratory CT image from the 10-phase 4DCT images was utilized for treatment planning. The CT of the most expiratory phase (50%) was used as the reference CT for treatment planning in clinical practice.

View this table:
Table I.

Patient characteristics.

Treatment planning. A radiation oncologist performed region of interest (ROI) contouring. The gross tumor volume (GTV) was delineated considering treatment planning CT images and magnetic resonance images, and the clinical target volume (CTV) was defined as the principle GTV with a 7-mm margin, plus an anatomical spread. The healthy liver region, excluding the GTV from the liver (liver-GTV) and the stomach, duodenum, colon, right kidney, and spinal cord, were depicted as organs at risk (OARs). RayStation 10A (RaySearch Laboratories, Stockholm, Sweden) was used as the treatment planning system. The treatment plan evaluated in this study was not the one used in clinical setting but was re-optimized according to our clinical protocols. The irradiation methods included raster scanning for transverse scanning and energy scanning for depth scanning (26). The prescription dose was 60 Gy in four fractions (19, 25), and the prescription method was the median dose prescription for CTV following our treatment protocol. All plans were established with two beams, and the optimization method was based on multifield sequential optimization. The beam was set up so that two beams were irradiated for each target when multiple tumors were located far apart. The pencil beam algorithm (27) was used for physical dose calculations for all plans, and a modified microdosimetric kinetic model was used for biological dose calculations (28, 29). This study did not set the planning target volume (PTV) and accounted for errors by applying robust optimization (30) to the CTV. Robust optimization parameters were set for CTV, and set up errors were compensated by 2 mm in all directions, but not for density uncertainty. This study did not consider respiratory movement measures because this study aimed to compare the treatment plans of the gantry and fixed-port plans, and the effects of respiratory migration would occur equally in both treatment methods. Three plans were developed for each patient: a rotating gantry plan (Gantry), a horizontal and vertical fixed irradiation port plan (Fix VH), and a horizontal and oblique 45° fixed irradiation port plan (Fix OH). All 360-degree angles were assumed to be available in the Gantry. The gantry angles were selected to specifically reduce the dose to the liver-GTV, and to keep the dose to other organs within clinically acceptable limits. For Fix VH and Fix OH, one horizontal beam and one vertical beam, and one horizontal beam and one 45° oblique port were assumed to be available, respectively. The beam angle for each port beam was determined to set the couch rolling within a range of ±20° as assumed in previous reports (31, 32). One medical physicist applied the same optimization parameters for all plans, but only the beam angle was changed. Table II shows the dose constraints set during the optimization process. A medical physicist with treatment planning experience, who performed the optimization considering the target and OAR doses, determined the feasible beam angle for each plan. Table I shows the gantry angles used in each plan and the number of beams. The number of beams was similar for each patient in each irradiation method.

View this table:
Table II.

Dose constraints for treatment planning optimization.

Evaluation. Dose–volume histogram (DVH) parameters in the three plans were compared. We evaluated the following DVH parameters: V98%, V95%, D2%, D98%, D50%, and homogeneity index (HI) for CTV; Dmean, V5Gy, V10Gy, V15Gy, V20Gy, V30Gy, V40Gy, and V50Gy for the liver-GTV; D1cc, and D6cc for the stomach, colon, and duodenum; V20Gy and Dmean for the right kidney; and D0.01cc for the spinal cord. Equation [1] was used to calculate HI.

IBM Statistical Package for the Social Sciences Statistics for Windows version 28 (IBM Corp., Armonk, NY, USA) was used for all statistical analyses for each DVH parameter to evaluate significant differences. The Friedman and Bonferroni test was used to calculate significant differences, with p-values of <0.05 indicating a significant difference.

Results

Table I shows the patient characteristics. The median GTV, CTV, and liver volumes were 121.8±279.8 cm3, 238.2±374.0 cm3, and 2188.7±383.2 cm3, respectively. Of the 30 cases, four patients had multiple tumors and each received multiple simultaneous irradiations. The treatment plan CT was obtained in the supine position in 23 cases and the prone position in seven cases.

Table III shows the DVH parameters for each plan. The target coverage parameter demonstrated CTV V95% of 95.5%±3.4%, 95.6%±3.5%, and 94.4%±5.2% for Gantry, Fix VH, and Fix OH, respectively, with no significant difference between them. No statistically significant differences were observed among the three plans for CTV and OARs, except for the liver-GTV. The representative values for liver-GTV were 12.2±6.5 Gy, 12.6±6.6 Gy, and 13.0±6.3 Gy for Dmean. The Gantry exhibited a decrease of 2.1%±3.8% and 3.4%±5.1% at V5Gy, 2.0%±3.5% and 3.0%±4.6% at V10Gy, and 1.5%±2.8% and 2.2%±3.6% at V15Gy, respectively, compared to Fix VH and Fix OH. A significant difference in the Dmean V5Gy, V10Gy, and V15Gy values of the liver-GTV was observed between the Gantry and the other two plans and in the V20Gy, V30Gy, and V40Gy values between the Gantry and Fix OH plans. Additionally, significant differences were observed in the V30Gy and V40Gy values between the Fix VH and Fix OH.

View this table:
Table III.

Average dose volume histogram (DVH) parameter values for all cases.

Figure 1 shows the mean DVH of all cases and the maximum and minimum DVH of all cases. The mean DVH for all ROIs did not significantly differ among the three plans. The lowest DVH curve for the CTV was lower for the Fix OH plan than for the other plans. The medium dose area for the liver-GTV was slightly lower in the Gantry than in the other two plans, particularly, with V30Gy of 18.0%±10.8%, 18.2%±10.9%, and 18.7%±10.7% for gantry, Fix VH, and Fix OH, respectively. A comparison of the maximum DVH values for the other OARs revealed higher values for the Gantry or Fix OH. The maximum DVH was higher in the Gantry than in the other plans, especially in the right kidney and spinal cord.

Figure 1.
Figure 1.

Dose volume histogram (DVH) of clinical target volume (CTV) and organ at risk (OAR) for each treatment plan. The solid and dotted lines indicate the mean DVH and the lowest or highest DVH among all cases, respectively.

Figure 2A and B show the dose distributions for patients 9 and 29, respectively. The gantry angle was adjusted to spare as much of the healthy liver as possible while shortening the beam path, resulting in a narrow low-dose area, because patient 9 had multiple targets. The V10Gy values of the liver-GTV in patient 9 were 38.9%, 43.3%, and 41.2% for the Gantry, Fix VH, and Fix OH, respectively. Patient 29 demonstrated only a single target, but the gantry angle adjustment resulted in a small spread of the medium-dose area within the liver. Figure 2B shows a rotating gantry that was used to set the angle at which the overlap of dose distributions could be reduced, thereby decreasing the spread of the intermediate-dose range. The V10Gy values of the liver-GTV in patient 29 were 14.6%, 17.3%, and 27.7% for the Gantry, Fix VH, and Fix OH plans, respectively.

Figure 2.
Figure 2.

Example of dose distribution and dose volume histogram (DVH) for each treatment plan. (A) and (B) are the dose distribution and DVH for patient 9 and patient 29, respectively.

Patient 27 had multiple tumors in the upper liver portion; thus, the beam angle was adjusted to ensure highly concentrated dose distribution to the tumors for an upper and lower slice (Figure 3). The target dose for the lower liver portion was less at the Fix OH beam angle because of the presence of the intestinal tract near the target. In the gantry and Fix V H plans, we were able to maintain target coverage while reducing the dose to the intestinal tract. The V95% values of the CTV were 92.4%, 92.3%, and 86.8% for the Gantry, Fix VH, and Fix OH, respectively. We used a rotating gantry to develop a tumor-limited dose distribution in the patients in whom various beam angles needed to be set depending on the intrahepatic localization of the tumor and its relationship to the OAR.

Figure 3.
Figure 3.

The upper and lower liver dose distributions for patient 27. The yellow arrow in Fix OH shows the decrease in dose in the target.

Discussion

This study used a rotating gantry to set the beam angle to assess the improvement in treatment planning in CIRT for patients with liver tumors. The results indicated that a rotating gantry significantly reduced the liver dose while maintaining the tumor dose and OAR dose compared with that of fixed-port irradiation. These results reveal that a rotating gantry may contribute to reduced toxicity in liver tumor CIRT.

Abe et al. and Shiba et al. performed a planning study comparing CIRT and X-ray therapy for liver tumors (33, 34). The values of liver-GTV DVH parameters in this study were between the values of liver DVH parameters shown in their study, respectively. One factor may be the target size. Abe et al. reported a 40.3 cm3 median GTV volume, whereas Shiba et al. demonstrated a 363.2 cm3 median PTV volume. Shiba et al. mentioned no GTV or CTV volume, and PTV was created by adding a 5-mm CTV margin to GTV, plus an internal margin and setup margin. In contrast, the median GTV volume and CTV volume of the patients analyzed in the current study were 121.8 cm3 and 238.2 cm3, respectively, which were generally between the sizes used in those previous studies. Therefore, the liver-GTV dose parameters were between those values, and the plans were considered comparable to those used in the two earlier studies. Additionally, both studies were based on fixed beamlines and passive irradiation. A reduction of >5 Gy in the Dmean of liver-GTV of the gantry plan in the present study was observed compared to that reported by Shiba et al. This may be due to the use of gantry and scanning irradiation.

Our study revealed that the use of a rotating gantry was particularly effective for reducing the low-dose liver-GTV. Additionally, the mean liver-GTV dose was significantly lower with the gantry, indicating a dose reduction effect. However, the mean value for each plan DVH parameter was not large; thus, our results did not indicate that treatment planning with a fixed-port was significantly inferior to the use of a rotating gantry. However, V5Gy was reduced by more than 3% in the gantry plan in 7 of 30 cases compared to Fix OH and in 9 of 30 cases compared to Fix VH. A significant difference in the relatively low-dose parameters of the V5Gy–V15Gy values for the liver-GTV was observed between the rotating gantry and fixed-port plans. The use of a rotating gantry is useful when low-to-moderate liver doses are desired.

Yan et al., Shielraw et al., and Kosaki et al. reported on the differences in treatment planning between fix and gantry ports in proton therapy (35-37). Similarly, this study revealed the limited parameters for which the gantry plan differed significantly from the fix port plan, and the small mean differences. The usefulness of the gantry for treatment planning was generally equivalent for both proton and CIRT. The study did not assess the robustness of the plan during the treatment period. Kosaki et al. mention the possibility of uncertainty reduction using gantry. Additionally, we did not evaluate non-coplanar irradiation, unlike Yan, and further research may characterize the gantry plan.

Koom et al. revealed that a rotating gantry system contributed to dose reduction in the surrounding organs for pancreatic cancer CIRT (38). Our study was similar to theirs in that we reduced the low-dose area of OAR despite differences in treatment sites.

Zhou et al. showed that the use of rotating gantry and appropriate gantry angle settings in the treatment of pancreatic cancer has the potential to minimize the deterioration of target coverage during the treatment period (39). Their study is based on passive irradiation, which differs from the scanning irradiation assumed in our study. It is not clear whether the results of their study are identical for scanning irradiation, but the characteristics of the carbon beam are similar and it would be possible to adapt the results. In such cases, the use of a rotating gantry would increase the likelihood of achieving both robustness in treatment planning and appropriate doses to the target and OARs.

Remash et al. revealed that irradiation can be performed without compromising the quality of the treatment plan, even without a CIRT rotation gantry, using the freedom of couch rotation and optimizing the beam incidence angle (40). Dose distribution considerations indicate that the difference between fixed and gantry ports is limited, but another advantage must be considered. Chinniah et al. mentioned that the use of the gantry in CIRT improves the quality of treatment planning, decreases patient burden by not couch rolling, and increases throughput due to decreased setup time (41). Patient and medical staff burden may exist, considering this background and benefits in both treatment planning.

Study limitations. First, all plans in this study were established according to the CT images obtained for a treatment couch with a rolling angle of 0°. The treatment couch is rolled when the beam angle is changed in fixed-port irradiation. The protocol for liver tumor treatment at our facility calls for the use of a rotating gantry, which eliminates the requirement for couch rolling. The position of the organs may change depending on the rolling angle of the couch that must be used in the actual fixed-port treatment. The use of CT images with couch rolling may provide a clearer advantage in treatment planning using a rotating gantry. Second, this study did not consider the uncertainty of the beam that passes through the couch. Kanai et al. quantified the amount of couch shift in positioning and reported that treatment planning beams that pass within a certain distance of the couch’s dense structure are uncertain during treatment (42). The planner should consider the uncertainty during irradiation and select a beam angle in actual treatment when selecting a beam to pass through the couch.

Conclusion

This study assessed the dosimetric impact on liver tumor cases comparing a rotating gantry versus fixed beamlines. In particular, the use of a rotating gantry reduces the low- to medium-dose area of the healthy liver. The use of a rotating gantry may be more useful in the case of multiple liver tumors or complex and variable positional relationships between the target and the OAR.

Acknowledgements

The Authors would like to thank the radiation oncologists, radiological technologists, and nurses involved in radiation therapy at Yamagata University Hospital. The Authors also thank the Accelerator Engineering Corporation for efficient accelerator operation and beam management at East Japan Heavy Ion Center. This work was supported by JSPS KAKENHI Grant Number JP 24K18533.

Footnotes

  • Authors’ Contributions

    Yuya Miyasaka: writing the manuscript, creating treatment plan and data analysis; Sung Hyun Lee: data analysis and review manuscript; Hikaru Souda: data analysis and review manuscript; Takashi Kaneko: contouring ROIs, clinical integration, clinical review and review manuscript; Yasuhito Hagiwara: contouring ROIs, clinical review and review manuscript; Hongbo Chai: review data and manuscript review; Miyu Ishizawa: review data and review manuscript; Hiraku Sato: clinical integration, clinical review and review manuscript; Takeo Iwai: management and coordination responsibility for the research activity planning and execution.

  • Conflicts of Interest

    The Authors declare that they have no conflicts of interest in relation to this study.

  • Received August 21, 2024.
  • Revision received September 10, 2024.
  • Accepted September 11, 2024.

This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY-NC-ND) 4.0 international license (https://creativecommons.org/licenses/by-nc-nd/4.0).

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Treatment Planning Comparison of Gantry-based and Fixed Beams for the Treatment of Liver Tumors With Carbon Ion Therapy
YUYA MIYASAKA, SUNG HYUN LEE, HIKARU SOUDA, TAKASHI KANEKO, YASUHITO HAGIWARA, HONGBO CHAI, MIYU ISHIZAWA, HIRAKU SATO, TAKEO IWAI
In Vivo Nov 2024, 38 (6) 3002-3010; DOI: 10.21873/invivo.13783
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