Hybrid Tomo‐Helical and Tomo‐Direct radiotherapy for localized prostate cancer

Abstract Purpose The aim of the study is to present a new planning approach to provide better planning target volume (PTV) coverage and reduce bladder and rectum dose with hybrid Tomo‐Helical (TH)/Tomo‐Direct (TD) radiotherapy (RT) for localized prostate cancer (LPC). Methods Twenty‐five LPC patients were included in this retrospective study. TH plans, TD plans, and hybrid TH/TD plans were created. Lateral beams were used for the hybrid TD plan and the prescribed dose was 70 Gy in 28 fractions (hybrid plans were combined 45 Gy/ 18 fxs for TH and 25 Gy/10 fxs for TD). Doses of PTV (D2%, D98%, D50%, homogeneity index (HI), conformity index (CI), coverage) and organs at risk (OARs) (V50%, V35%, V25%, V5%, and V95%) were analyzed. The Wilcoxon signed‐rank test was used to analyze the difference in dosimetric parameters. p‐Value < 0.05 was considered statistically significant. Results TH plans showed better CI, and target coverage (p < 0.01) than TD and hybrid plans in all patient plan evaluations. However, TD plans D2%, D98%, and D50% doses were better than TH and hybrid plans. The HI values were similar between the three plans. Significant reductions in bladder and rectum V50%, V35%, and V25% doses (p < 0.001) were observed with hybrid plans compared to TH and TD. Penile bulb V95% and bowel V5% doses were better in the hybrid plans. Left and right femoral head V5% doses were higher in the hybrid plan compared to others (p < 0.001). Conclusion Concurrently hybrid TH/TD RT plan can be a good option to reduce the doses of the rectum and bladder in the RT of LPC.


INTRODUCTION
High-dose moderate hypofractionation RT is thought to reduce the effect of tumor cell repopulation 12 and improve treatment outcomes in the RT of LPC. [13][14][15][16][17] Tomotherapy (Accuray Inc.) is an RT device with IGRT capability by taking daily Megavoltage Computed Tomography scan before treatment. 18 Tomotherapy has different version treatment devices and one of them is TomoHDA. TomoHDA treatment system was produced after TomoTherapy-Hi-Art and TomoHD technologies. The first treatment with TomoHDA was performed at Center Oscar Lambret in Lille, France in 2013. Tomo-HDA system offers the user the chance to treat patients in two different modes. Tomo-Helical (TH) mode provides a continuous 360 • beam that may result in optimal dose distribution and dose conformity. 19 The Tomo-Direct (TD) mode is a non-rotational treatment option of the Tomotherapy platform and provides treatment at predetermined angles with a fixed gantry. 20,21 Tomo-HDA provides faster and better dose distribution with the new technology IDMS (integrated data management system) with Precision Planning System. 22 In this study, we aimed to develop a new planning approach by creating simultaneous hybrid TH/TD treatment plans for LPC patients undergoing high-dose RT with TomoHDA. We intended to reduce the doses of OARs such as bladder and rectum by increasing target dose homogeneity with the hybrid technique.

Patient selection and contouring
In this study, we used image data of 25 patients with a diagnosis of LPC. The patients who were treated for LPC using Elekta Synergy Platform linear accelerator and Tomotherapy HDA between June 2018 and September 2020, were retrospectively analyzed. The patients were instructed to drink 500-750 ml of water 45 min before the CT scan (as our clinical protocol). Patients were asked to empty their bladder before treatment and were provided to be treated with an empty rectum. Patients were placed in the head-first supine position and 2.5 mm slice thickness computed tomography (CT scan GE-Light Speed 64 Discovery RT 16 Slice; GE) was performed on the T-board in the supine arm up position. Magnetic resonance images were performed by a 3T whole-body system (Spectra; Siemens-Healthcare). Radiation oncologists contoured all targets and OARs of LPC patients. The whole prostate contoured as clinical target volume and planning target volume (PTV) generated by clinical target volume plus 5 mm posteriorly and 10 mm in other directions. Contouring of PTV and OARs were performed by using a CT scan with a 2.5 mm slice thickness and magnetic resonance images fusion. Rectum, bladder, bowel, femoral heads, and penile bulb were contoured as OARs. Rectum was contoured from ischial tuberosities to rectosigmoid flexure and femoral heads inferiorly to the bottom of ischial tuberosities. Urinary bladder contoured from its base to the dome and penile bulb contoured immediately inferior to the genitourinary diaphragm. 23

Treatment planning
TH, TD, and hybrid TH/TD plans were created in the Tomotherapy HDA IDMS Precision Planning System (version 2.0.1.1 [5]; Accuray Inc.) for each patient. All plans were normalized to cover 95% of the PTV, and 70 Gy delivered at Gy 2.5 Gy/fraction in 28 fractions. 24 Various parameters can be used in the tomotherapy planning station optimization panel.One of the optimization parameters is the importance and the other one is the penalty. Critical organs are listed in order of priority.
For the plans to be comparable, the same parameters (priority, importance, maximum dose penalties, and minimum dose penalties) were determined in both TH and TD plans (
The TH IMRT plans were generated with helical dynamic jaw mode The field width, pitch, and modulation factor values were 2.5 cm, 0.314, and 2.0, respectively. The prescribed dose was 70 Gy in 28 fractions.
The hybrid tomotherapy plans were a combination of TH and TD plans. HD planning dose provided approximately two-thirds of the total dose. TD planning dose provided approximately one-third of the total dose. 25 Gy delivered at 2.5 Gy/fraction in 10 fractions. Seven lateral beams were used with gantry angles of 77 • , 86 • , 101 • , 110 • , 250 • , 275 • , and 300 • . The prescribed dose was 45 Gy in 15 fractions and sum plans of TH/TD plans were determined.

Dosimetric evaluation
Plan evaluations were based on dose-volume histogram (DVH) analysis. To evaluate the dose distribution TA B L E 1 Planning priority, importance, maximum (max) dose penalty, minimum (min) dose penalty, max dose, dose-volume histogram (DVH) volume (%), and DVH dose (Gy) for planning target volume (PTV) and organs at risk (OARs)

Structures
Overlap priority Importance of the target, parameters were calculated for PTVs: the absolute dose received by the 2% (D2%), the absolute dose received by the 50% (D50%), the absolute dose received by 98% (D98%; ICRU 83). 25 Conformity index (CI) is the ratio of total tissue volume that receives the prescription isodose or more to the target volume that receives the prescription isodose. 26 where V RI is the volume covered by the prescribed dose and TV is the target volume. Homogeneity index (HI) is the ratio of the maximum dose to the prescription dose. 26 where D max is the maximum dose of the target volume and D p is the prescription dose of the target volume.

Statistical analyses
Statistical analyses were performed with SPSS 18.0 (Statistical Package for the Social Sciences; SPSS Inc.). The Wilcoxon signed-rank test was used to compare the dose parameters of the TD and TH plans. All p-values below 0.05 were considered statistically significant.

RESULTS
In this study, we investigated whether there was a statistically significant difference in dosimetric values between the TH-TD, TH-hybrid TH/TD, and TD-hybrid TH/TD plans. Tables 2-4  . The hybrid TH/TD plans provided statistically significant sparing for both the bladder and rectum at all V50(%), V35(%), and V25(%) values (p < 0.01). At the same rectum and bladder, the V15(%) value of the hybrid TH/TD plan is more advantageous than TH and TD plans. The right femoral head and left femoral head V5% doses were statistically significantly higher in the hybrid TH/TD plan compared to TH and TD (p < 0.001). We found no significant difference for the bowel V5% and penile bulb V95% among the three plans (p > 0.05). But bowel V5% and penile bulb V95% hybrid TH/TD plan value was the lowest value when compared with other plans. A comparison of axial and sagittal dose distribution of LPC patients for TH, TD, and hybrid TH/TD plan is shown in Figure 1.

DISCUSSION
The prostate is located below the bladder and in front of the rectum and gastrointestinal and genitourinary toxicity may occur in hypo-fractionated RT applications to prostate cancer. 27 In prostate RT, toxicity is related to TA B L E 2 Dose-volume histogram (DVH) parameters (mean ± standard deviation) for planning target volume (PTV) and organs at risk (OARs) with p-values for comparison of Tomo-Helical (TH) and Tomo-Direct (TD) the volume irradiated. 28 In this study, we obtained hypofractionated RT plans by using the planning options in two different modes of (TH and TD) separately and together with a certain combination in the HDR tomotherapy. We chose lateral gantry angles for TD to reduce the rectum and bladder dose while creating a hybrid combination. While determining the lateral angles, we tried to choose them according to the anatomy of the patients by using our clinical experience. While generating lateral gantry angles, we encountered an increase in femoral head doses.There are few data to explain femoral toxicity when higher doses are given to small volumes of the femoral heads. Generally,tolerance of entire femoral heads was limit to V50 Gy < 5%. 29 We tried different fraction combinations for the hybrid plans. We have seen that approximately two-thirds of the ratio of TH and one-third of the TD hybrid plan provides a significant reduction in the bladder and rectum doses.
In this way, we were able to limit V50 Gy < 5% without increasing the femoral head dose too much.
There are different types of cancer studies with clinical and dosimetrically outcomes reported in patients treated with hybrid RT. Balaji et al. showed the best treatment plan combination would be achieved with 70%-80% 3D-IMRT and 20%-30% arc in the hybrid breast RT. 30 Similarly, Venjakob et al. determined that the hybrid VMAT technique (combination with 80% 3D-CRT/20% VMAT) has positive advantages in RT of breast cancer. 31 TA B L E 3 Dose-volume histogram (DVH) parameters (mean ± standard deviation) for planning target volume (PTV) and organs at risk (OARs) with p-values for comparison of Tomo-Helical (TH) and hybrid plans  32 Silva et al. presented the clinical application of the hybrid Rapid Arc in patients with locally advanced lung cancer. Hybrid Rapid Arc plans were created with the combination of static (60%) and Rapid Arc (40%) beams and showed advantages for reducing the OARs dose. 33 We tried different fraction combinations for the hybrid plans in this study. We conclude that 45 Gy/18 fxs for TH and 25 Gy/10 fxs for TD is the best combination. The number of studies involving hybrid RT of prostate cancer is limited in the literature. The study of Amaloo et al.compared VMAT plans with hybrid plans in prostate patients. 34 They determined that hybrid plans yielded fewer rectum and bladder doses in almost all cases. Similarly, in our study, we found statistically significant lower doses in the rectal and bladder in hybrid plans. Penile bulb and bowel doses were lower in hybrid plans too. The study of Robar et al. stated that the Hybri-dArc method provides various advantages in different anatomical regions and increases PTV dose homogeneity for prostate treatment. 35 In a study examining prostate cancer hybrid IMRT and volumetric modulated arc treatment plans, the 25% IMRT technique increased target dose homogeneity and provided rectum protection. 36 In the current study, as we used beams containing lateral gantry angles used when trying to lower bladder and rectum doses, the hybrid TH/TD plan CI value was statically significantly higher than TH and TD (p < 0.001). Also, all planning methods (TD, TH, and hybrid) provided good coverage (%). There was a significant increase in femoral head V5% dose in hybrid plans compared to TH and TD plans (p < 0.001). Similarly, Amaloo et al. determined that there was an increase in TA B L E 4 Dose-volume histogram (DVH) parameters (mean ± standard deviation) for planning target volume (PTV) and organs at risk (OARs) with p-values for comparison of Tomo-Direct (TD) and hybrid plans  34 There are some studies in the literature comparing TH and TD plans of the tomotherapy system. Davidson et al. compared seven-angle static IMRT plans with TH plans for prostate patients and found conventional IMRT plans were similar to TH. 37 In the study of Murai et al., they compared five static gantry angled TD plans with TH plans and found the dose to the rectum in TD plans was significantly higher than TH plans. 20 In our study, the rectum doses were similar between TH and TD but bladder V50 and V35 doses were found to be statistically significantly lower in TH plans compared to TD (p < 0.001).
There are several limitations of our study. First of all, we used a small number of patient dosimetric data. The other limitation of this study was similar tomotherapy plans were obtained with fixed gantry angle, iterations, and optimization criteria. Considering that each patient has different PTV, OARs, and anatomical deviations, a specific treatment plan could not be obtained for each patient. Besides, creating and evaluating hybrid plans can cause extra workload for clinics (planning time, delivery quality assurance, etc.). In addition, more research is required on the clinical outcomes of LPC patients treated with hybrid TH/TD. In order to overcome these limitations, large-scale clinical studies can be carried out with a large number of patients and special plans can be made for each patient. Clinics can start the application with the determined standard data without extra workload.

CONCLUSION
In this study, we presented a new hybrid delivery method for LPC in HDA tomotherapy. The use of lateral beams Our study showed the advantages of reducing bladder and rectal doses of the hybrid TH/TD method compared to the TH and TD methods. This study may shed light on studies aimed at reducing critical organ dose in hypofractionated prostate RT, which is expected to become widespread in the future.

C O N F L I C T O F I N T E R E S T
The authors declare that they have no conflict of interest.

E T H I C A L A P P R OVA L
Our study was approved by the Akdeniz University Faculty of Medicine Ethics Committee of Clinical Trials (2020 -KAEK-813). The study was a retrospective review so subject informed consent was not obtained.