Journal of Radiation Research, Vol. 61, No. 3, 2020, pp. 487–493
doi: 10.1093/jrr/rraa013
Advance Access Publication: 25 March 2020

Comparison of rectal dose reduction by a hydrogel
spacer among 3D conformal radiotherapy,
volumetric-modulated arc therapy, helicaltomotherapy, CyberKnife and proton therapy
Masahide Saito1, *, Toshihiro Suzuki2 , Yuya Sugama3 , Kan Marino1 , Naoki Sano1 ,Takafumi Komiyama1 , Shinichi Aoki1 , Yoshiyasu Maehata1 , Kazuya Yoshizawa1 ,Kazunari Ashizawa1 , Hidekazu Suzuki1 , Koji Ueda1 , Yosuke Miyasaka1 ,Masayuki Araya3 , Hiroshi Takahashi2 and Hiroshi Onishi1
1 Department of Radiology, University of Yamanashi, Yamanashi, Japan
2 Kasugai CyberKnife Rehabilitation Hospital, Yamanashi, Japan
3 Aizawa Hospital Proton Therapy Center, Matsumoto, Japan*Corresponding author. Department of Radiology, University of Yamanashi, 1110 Shimokato, Chuo-city, Yamanashi, 409-3898, Japan.
Tel: +81-55-273-1111; Fax: +81-55-273-6744; Email: masahides@yamanashi.ac.jp(Received 9 December 2019; revised 27 January 2020; editorial decision 15 February 2020)

ABSTRACTThis study aimed to evaluate the rectal dose reduction with hydrogel spacer in 3D conformal radiotherapy (3DCRT),
volumetric modulated arc therapy (VMAT), helical tomotherapy (HT), CyberKnife (CK) and proton therapy.
Twenty patients who had hydrogel spacer for prostate radiotherapy were retrospectively enrolled. Computed tomography (CT) images with or without hydrogel spacer were used to evaluate rectal dose reduction. In total, 200 plans(20 patients × 2 CT images × 5 techniques) were created using the following criteria: 3DCRT, VMAT and HT[76 Gy/38 fractions (Fr), planning target volume (PTV) D50%], CK (36.25 Gy/5 Fr, PTV D95%) and proton
therapy (63 GyE/21 Fr, PTV D50%). Rectal dose reduction was evaluated using low-/middle-dose (D20%, D50%
and D80%) and high-dose (D2%) ranges. Rectal dose reduction of each dose index was compared for each technique.
Significant rectal dose reduction (P < 0.001) between the treatment plans on pre- and post-CT images wereachieved for all modalities for D50%, D20% and D2%. In particular, the dose reduction of high-dose (D2%) ranges
were −40.61 ± 11.19, −32.44 ± 5.51, −25.90 ± 9.89, −13.63 ± 8.27 and −8.06 ± 4.19%, for proton therapy, CK,
HT, VMAT and 3DCRT, respectively. The area under the rectum dose–volume histogram curves were 34.15 ± 3.67
and 34.36 ± 5.24% (P = 0.7841) for 3DCRT with hydrogel spacer and VMAT without hydrogel spacer, respectively.
Our results indicated that 3DCRT with hydrogel spacer would reduce the medical cost by replacing the conventional
VMAT without spacer for prostate cancer treatment, from the point of view of the rectal dose. For the high-dose
gradient region, proton therapy and SBRT with CK showed larger rectal dose reduction than other techniques.
Keywords: hydrogel spacer; prostate cancer; rectum dose; CyberKnife; proton therapy

INTRODUCTION
A high conformal external beam radiotherapy (EBRT) is conventionally used to treat patients with low or intermediate risk for prostatecancer and shows favorable treatment outcomes compared withsurgery [1]. Currently, many EBRT techniques are available, such as 3D
conformal radiotherapy (3DCRT), intensity-modulated radiotherapy(IMRT), volumetric modulated arc radiotherapy (VMAT), stereotactic body radiotherapy (SBRT) and proton therapy. Although dose

© The Author(s) 2020. Published by Oxford University Press on behalf of The Japanese Radiation Research Society and Japanese Society for Radiation Oncology.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which
permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

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M. Saito et al.

escalation with these techniques leads to a better treatment outcome[2, 3], toxicities on the rectum are still an important problem especiallywith 3DCRT [4]. As one of the solutions to reduce rectal dose, ahydrogel spacer (SpaceOARTM System, Augmenix Inc., Waltham, MA)
has been introduced and used for EBRT in prostate cancer patients. A
phase 3 trial for image-guided IMRT shows the benefit of a hydrogel
spacer in reducing rectal dose, toxicity and quality of life decline [5].
A number of studies reported the effectiveness of treatment planning using the hydrogel spacer [6–8]. Although the effect of rectal
dose reduction is well-known, the characteristics of different EBRT
techniques have not been evaluated in detail, and the difference inthe effects of irradiation methods is unclear. In particular, one of ourimportant hypotheses is that 3DCRT with hydrogel spacer might show
comparable dose distribution with VMAT without hydrogel spacer.
This hypothesis is important especially for some facilities where IMRT
is not possible. Therefore, this study aimed to evaluate rectal dose
reduction with hydrogel spacer in five types of EBRT techniques:
3DCRT, VMAT, helical tomotherapy (HT), CyberKnife (CK) andproton therapy.

Contouring and treatment planning protocol
Three medical physicists contoured all organs at risk (OARs) andtargets and created all plans. For OARs, the rectum [contoured ±5
CT slices from PTV (thickness of CT slice, 2 mm)], bladder andurethra were contoured. In a clinical setting, the clinical target volume(CTV) in our protocol was different between risk classifications: highrisk, prostate plus 2 cm of the seminal vesicle for cases lower thanT3b, or total seminal vesicle invasion with satisfactory margin for T3bcases; intermediate risk, CTV plus 1 cm of the base of the seminal
vesicles; and low risk, prostate. However, only four high-risk patientswere included in this study; therefore, all CTV was set as low risk
to reduce treatment plan variability due to target-shape complexity.
Additionally, the PTV margin setting and beam arrangement weredifferent among the five techniques, which is explained as following
section. The treatment plans were created for CT images of SO(−) andSO(+) for five irradiation techniques, respectively, i.e. 20 patients × 2
CT images × 5 irradiation techniques; thus, a total of 200 plans werecreated.

3DCRT

Procedure

Treatment planning was performed by Pinnacle TPS (Philips Radiation Oncology Systems, Madison, WI)) using Elekta Synergy
with Agility gantry head, which has 160 multi-leaf collimator leavesof 5 mm (Elekta AB, Stockholm, Sweden). Isocenter of the beams was
located at the center of PTV. All patients received a dose covering 50%
volume (D50%) prescription of 76 Gy for PTV in 38 Fr. The adaptive
convolve in Pinnacle was used as the dose calculation algorithm, andthe dose grid size was 2.5 mm for all dimensions. The PTV margin
from the CTV was defined as 8 mm in the anterior and superior; 5 mmin the left, right and inferior; and 4 mm in the posterior directions.
Five fixed beams (0, 75, 120, 240 and 285◦ ) were used with 10 MV
X-ray. For all beams, the collimator angle was 0◦ and a port margin was
created by 5-mm PTV expansion. The doses of the rectum and bladderwere reduced as much as possible.

All patients were treated with SBRT [36.25 Gy/5 fractions (Fr), planning target volume (PTV) D95%] in CK or hypofractionated treatment with IMRT (62 Gy/20 Fr, PTV D50%) in HT following hydrogel
implantation. The hydrogel implantation method has previously been
described [6, 9]. In our institute, the spacer was inserted by radiation
oncologists. In brief, the patient is positioned in the dorsal lithotomy
position with a transrectal ultrasound probe positioned in the rectum.
Then, a needle is subsequently advanced to the midpoint (base toapex) of the prostate gland, and the spacer is injected between therectum and prostate under transrectal ultrasound guidance and a stepper device. The spacer solidifies in seconds and it maintains a space
between the prostate and the rectum for ∼3 months. Finally, the spacer
is absorbed into the body over ∼6 months.
The study was performed with the following procedure. First, computed tomography (CT) images at pre-SpaceOAR injection [SO(−)]
were acquired for all patients. After the injection, CT images with theSpaceOAR [SO(+)] were acquired. Note that the condition of thepatient setup for each image acquisition was slightly different because
spacer placement took 30–60 min. After obtaining each CT image, five
types of treatment planning were performed by three clinical medical
physicists, and statistical analysis was performed.

For VMAT, treatment planning was performed by Pinnacle TPS using
the SmartArc optimization algorithm. Treatment machine, dose calculation algorithm, dose grid size and PTV margin setting were the sameas in the aforementioned 3DCRT conditions. Beam energy was 10 MV,
and one full arc (181 to 179◦ clockwise) with a collimator angle of 15◦
was used. All patients received a dose covering 50% volume (D50%)
prescription of 76 Gy for PTV in 38 Fr. The dose constraints of the rectum were D2% < 74.4 Gy, D10% < 66.5 Gy and D50% < 20.0 Gy. The
dose constraints of the bladder were D15% < 73 Gy, D25% < 70 Gy,
D35% < 67 Gy and D50% < 57 Gy.
For HT, treatment planning was performed by Tomotherapy Planning Station (Accuray, Sunnyvale, CA) and TomoHD (Accuray, Sunnyvale, CA) was used as the treatment machine. The plans for HT
were created with a dynamic jaw mode using a jaw size of 2.51 cm andpitch size of 0.287 cm in all cases. The convolutional/superposition
algorithm with the fine dose grid was used as the dose calculation
algorithm. The dose prescription and dose constraints were the sameas those in VMAT.

MATERIALS AND METHODS

Study design
This retrospective study was approved by the institutional review
board (IRB) of the University of Yamanashi. From July 2018 toMarch 2019, 20 patients who underwent prostate radiotherapy witha hydrogel spacer (SpaceOARTM System, Augmenix Inc., Waltham,MA) were enrolled. In this study, the eligibility criteria for hydrogel
spacer implantation were as follows: (i) case with SBRT, (ii) patientswith a high risk of hemorrhage such as those with diabetes mellitus or
receiving anticoagulants and (iii) patients with large prostatic volume
near the rectum.

VMAT and HT

Rectal dose reduction with a hydrogel spacer

•

489

CK

RESULTSThe SBRT plan was created for all patients using CyberKnife MultiPlan TPS (Accuray, Sunnyvale, CA) with a sequential optimization
algorithm. CyberKnife G4 (Accuray, Sunnyvale, CA) with Fixed andIris collimator was used as the treatment machine. All plans typicallyused 2–3 fixed collimators of different sizes and 150–300 noncoplanar and non-isocentric beams of 6 MV. The prescription dose wascalculated using the Monte Carlo algorithm with a 2% uncertainty
on a 1 × 1 × 1.25-mm resolution. The PTV margin from the CTV
was defined as 3 mm in the posterior direction and 5 mm in otherdirections. All patients received a dose covering 95% volume (D95%)
prescription of 36.25 Gy for PTV in 5 Fr. The dose constraints of
the rectum and bladder were D1cc < 35.0 Gy and D1cc < 39.0 Gy,
respectively.

This study included 20 patients who underwent prostate radiotherapy
with the hydrogel spacer. Considering baseline characteristics, the risk
classification was high in 4 cases, intermediate in 14 cases and low in
2 cases. The prostate specific antigen (PSA) was 9.81 ± 4.88 ng/mL,
the mean Gleason score was 7.15 ± 1.24 and the mean patient age was
72.6 ± 6.1 years. In this study, the average CTV for all patients was
30.1 ± 11.4 mL. Table 1 shows the PTV dose indices for all treatment
techniques. For most of the PTV dose indices, no significant difference
was noted between SO(−) and SO(+), while there was a significant
difference between some dose indices (P < 0.01; VMAT D98% andD95%, and CK D50% and D2%). However, we found that the dose
differences themselves were small and had no effect on the PTV dosecoverage in a clinical situation.
Figure 1 shows the results of the average DVH of the rectum in 20
patients for five modalities: (a) 3DCRT, (b) VMAT, (c) HT, (d) CK
and (e) proton. The red and blue solid lines show the results of SO(−)
and SO(+), respectively. The dose index of the rectum and bladder forthe treatment plans on SO(−) and SO(+) are shown in Tables 2 and3, respectively. For the rectum, significant differences (P < 0.001) in
D2%, D20% and D50% were observed for all irradiation techniques.
However, D80% did not show significant difference between the treatment plans on SO(−) and SO(+). For the bladder, no significant
difference was found between the techniques. From another point ofview, Figure 2 shows the comparison of DVHs of rectal dose between
3DCRT and VMAT. Table 4 shows the comparison of the rectal dose
between them, and the values of D2% and D20% of 3DCRT [SO(+)]
were significantly (P < 0.001) lower than that of VMAT [SO(−)]. Furthermore, the areas under the rectum DVH curves were 34.15 ± 3.67
and 34.36 ± 5.24% (P = 0.7841) for 3DCRT with hydrogel spacer and
VMAT without hydrogel spacer, respectively. For all modalities, typicaldose distributions of SO(−) and SO(+) are shown in Figure 3.
Figure 4 shows the rectal dose reduction rate using hydrogel
spacer in the five techniques. All rectum dose indices of all techniques
trended to reduce by using SO. Except for D80%, significant difference(ANOVA P-value < 0.0001) was noted between the five techniques.
In particular for D2%, according to the Tukey–Kramer test, the rectal
dose changed at −40.61 ± 11.19, −32.44 ± 5.51, −25.90 ± 9.89,−13.63 ± 8.27 and −8.06 ± 4.19%, for proton therapy, CK, HT,
VMAT, and 3DCRT, respectively.
Furthermore, the correlation between the effectiveness of usinghydrogel spacer and tumor size was evaluated for all treatment
techniques. Table 5 shows the Spearman’s rank correlation coefficient
between the rectal dose reduction rate and CTV volume. No
correlations were found between them for all irradiation techniques.

Proton therapy
Treatment plans for the line-scanning proton therapy were created by
Eclipse TPS (Varian Medical Systems, Palo Alto, CA). Proton therapy was performed by a cyclotron (Sumitomo Heavy Industries, Ltd.,Tokyo, Japan). Two opposite beams (90 and 270◦ ) with multiple layer
scanning capacity were used. All patients received a dose covering
50% volume (D50%) prescription of 63 GyE for PTV in 21 Fr. The
proton convolutional superposition was used as the dose calculation
algorithm, and the dose grid size was 2.0 mm for all dimensions. The
PTV margin was defined as the CTV plus internal margin (IM) plus
3-mm set-up margin (SM). The IM was 5 mm in the anterior direction
and 3 mm in other directions. The distal margin was 7 mm beyond thePTV, which was set as 3.5% of the maximum required range distance.
The dose constraints of the rectum were V60 Gy <10%, V50 Gy < 20%
and V30 Gy <30%. The dose constraints of the rectum were volume
covered by 60 Gy (V60 Gy) <10%, V50 Gy < 20% and V30 Gy <30%.

Evaluation and statistical analysis
First, we performed a global comparison using the areas of the rectum
dose–volume histogram (DVH) curve of each patient (area undercurve, AUC) as variable [10], and the mean AUCs among the techniques were compared using Wilcoxon’s test. Second, for all treatment
plans, the doses received by at least 80, 50, 20 and 2% (D80, D50,
D20 and D2% respectively) of the rectum and bladder were calculated,
and the dose indices were compared between SO(+) and SO(−) by
Wilcoxon’s test. The reduction rate of the rectal dose was calculatedusing the following equation:

Reduction rate (%) =Dpost − Dpre
Dpost


× 100

DISCUSSION,where Dpre was the rectum dose in SO(−) and Dpost corresponded tothat in SO(+). Then, we compared the reduction rates between the fivetechniques by analysis of variance (ANOVA) and Tukey–Kramer tests.
All image and dose analyses were performed in MIM Maestro software(Cleveland, OH). All statistical analysis was performed by JMP Pro
ver 14.0 (SAS Institute Inc., Cary, NC) with the level of significanceat P < 0.01.

Recently, both conventional treatment in 2 Gy/Fr and SBRT withhigh dose fraction have been used for localized prostate cancer treatment [11, 12]. The constraints of the rectum dose may be different
depending on fractioned doses and total doses; therefore, it should
comply with the dose constraints conforming to the fractionation,with or without SO. To the best of our knowledge, no studies havecompared various types of external radiotherapy techniques for rectal dose reduction using SpaceOARTM . Therefore, in this study, we490 •

M. Saito et al.

Table 1. Dose index of the PTV for the treatment plans on pre- and post-CT images and the results for the five irradiation
techniques
Absolute dose (mean ± SD, Gy or GyE)
D98%

3DCRT
VMAT
HT
CK
Proton

D95%

D50%

D2%

SO(−)

SO(+)

P-value

SO(−)

SO(+)

P-value

SO(−)

SO(+)

P-value

SO(−)

SO(+)

P-value

71.2 ± 0.8
71.6 ± 1.9
71.6 ± 1.8
35.5 ± 1.0
57.9 ± 2.9

71.2 ± 1.1
73.5 ± 1.6
72.5 ± 1.5
35.1 ± 0.4
58.6 ± 2.5

0.70120.00030.06370.379
0.043

72.5 ± 0.5
73.5 ± 1.2
73.8 ± 1.3
36.2 ± 0.2
59.8 ± 2.1

72.6 ± 0.6
74.2 ± 1.1
74.3 ± 0.8
36.2 ± 0.2
60.3 ± 1.6

0.41420.00090.12310.86180.031975.9 ± 0.3
76.1 ± 0.0
76.4 ± 0.1
39.8 ± 1.2
63.5 ± 0.3

76.0 ± 0.4
76.1 ± 0.1
76.4 ± 0.1
40.4 ± 0.8
63.6 ± 0.4

0.041
0.82040.36340.00530.905578.1 ± 0.8
77.5 ± 0.4
77.8 ± 1.0
45.1 ± 1.6
65.8 ± 0.4

78.6 ± 0.8
77.5 ± 0.4
77.9 ± 0.8
46.0 ± 1.3
65.5 ± 0.8

0.04840.2196
0.36830.00620.4467

Fig. 1. Average dose–volume histogram (DVH) of the rectum in 20 patients and the results of five modalities: (a) 3DCRT, (b)VMAT, (c) HT, (d) CK and (e) proton. Red and blue solid lines show the result of SO(−) and SO(+), respectively.
compared the efficacy of spacer placement between five irradiation
techniques, and some interesting results were obtained. First, the DVH
curves of 3DCRT with hydrogel spacer and VMAT without hydrogel

spacer were almost the same because of the AUC analysis (Fig. 2 andTable 4). Furthermore, for high- and middle-dose regions (D2% andD20%), the former showed significantly lower rectal dose than theRectal dose reduction with a hydrogel spacer•

491

Table 2. Dose index of the rectum for the treatment plans on pre- and post-CT images and the results for the five irradiation
techniques
Absolute dose (mean ± SD, Gy)
D80%

3DCRT
VMAT
HT
CK
Proton

D50%

D20%

D2%

SO(−)

SO(+)

P-value

SO(−)

SO(+)

P-value

SO(−)

SO(+)

P-value

SO(−)

SO(+)

P-value

8.64 ± 5.64
5.66 ± 2.21
6.67 ± 4.26
6.71 ± 1.73
0.12 ± 0.14

8.98 ± 6.85
4.98 ± 2.11
6.65 ± 4.69
5.38 ± 1.86
0.09 ± 0.08

0.67420.12310.47490.00050.269927.05 ± 5.19
17.27 ± 4.04
22.21 ± 3.81
13.87 ± 2.83
1.94 ± 1.32

22.29 ± 3.76
11.38 ± 3.75
17.48 ± 5.17
9.76 ± 2.13
0.91 ± 0.41

<0.0001<0.0001<0.0001<0.0001<0.000161.47 ± 6.92
49.78 ± 5.32
44.49 ± 5.45
25.50 ± 3.72
23.29 ± 7.15

40.08 ± 6.10
31.90 ± 6.91
30.15 ± 5.64
15.83 ± 2.34
7.15 ± 2.61

<0.0001<0.0001<0.0001<0.0001<0.0001

74.26 ± 0.89
72.39 ± 1.70
73.36 ± 7.83
36.10 ± 1.52
61.35 ± 3.10

68.14 ± 3.19
62.03 ± 7.04
53.68 ± 7.26
24.33 ± 1.81
35.77 ± 6.51

<0.0001<0.0001<0.0001<0.0001<0.0001

Table 3. Dose index of the bladder for the treatment plans on pre- and post-CT images and the results of five irradiation techniques
Absolute dose (mean ± SD, Gy)
D80%
SO(−)
3DCRT
VMAT
HT
CK
ProtonSO(+)

D50%
P-value16.02 ± 15.26 15.34 ± 14.70 0.7841
18.52 ± 11.55 17.65 ± 12.12 0.2943
15.30 ± 10.99 15.31 ± 11.32 0.6742
13.41 ± 4.74 12.00 ± 5.56 0.114
3.17 ± 4.57 2.68 ± 3.04 0.5459

SO(−)

SO(+)

D20%
P-value

36.80 ± 17.29 34.36 ± 21.74 0.4304
41.52 ± 14.22 39.29 ± 17.14 0.3488
38.54 ± 13.22 33.32 ± 16.05 0.0897
19.94 ± 5.80 19.21 ± 6.69 0.436
15.55 ± 13.87 16.48 ± 13.87 0.9854

SO(−)

SO(+)

D2%
P-value

66.01 ± 8.78 63.64 ± 13.44 0.6742
69.30 ± 5.52 68.19 ± 10.45 0.8695
65.79 ± 6.61 62.38 ± 11.84 0.2305
30.85 ± 4.18 29.83 ± 6.03 0.4749
43.97 ± 11.79 43.80 ± 14.67 0.9563

SO(−)

SO(+)

P-value

76.72 ± 1.35
76.53 ± 0.38
76.82 ± 0.27
39.87 ± 0.77
64.71 ± 0.42

77.17 ± 1.25
76.49 ± 0.59
76.95 ± 0.54
39.90 ± 0.89
64.72 ± 0.55

0.29430.81940.46920.953
0.6944

Table 4. Comparison of the rectal doses and AUC between
VMAT without hydrogel spacer [SO(−)] and 3DCRT withhydrogel spacer [SO(+)]
Absolute dose (mean ± SD, Gy)
VMAT, SO(−)
D2%
D20%
D50%
D80%
AUC

Fig. 2. Comparison of DVHs of the rectal dose between
3DCRT and VMAT. Dotted line shows VMAT [red: SO(−),
blue: SO(+)] and solid line shows 3DCRT [red, SO(−); blue,
SO(+)].
latter. This has not been mentioned in previous reports. Many facilities
are still implementing 3DCRT to prostate cancer, because no highprecision machine is available and clinical staff are limited. Our results
provide useful evidence with regard to such facilities, indicating thatthe former technique might be used instead of conventional VMAT as
treatment for prostate cancer in such facilities. However, it is noted that
VMAT has more benefit than 3DCRT for dose painting in PTV, suchas decreasing urethra dose or increasing dose in high-risk regions.
Second, our results showed that the rectal dose reduction in thehigh-dose region such as D2% depended on the irradiation technique.
In particular, proton therapy has Bragg peak that shows potential benefit compared with X-ray therapy; thus, it has high gradient dose distribution and larger rectal dose reduction than other techniques. Furthermore, some previous reports mentioned the safe use of the spacer

3DCRT, SO(+)

72.39 ± 1.70
68.14 ± 3.19
49.78 ± 5.32
40.08 ± 6.10
17.27 ± 4.04
22.29 ± 3.76
5.66 ± 2.21
8.98 ± 6.85
Area under curve (%)
34.15 ± 3.67
34.36 ± 5.24

P-value
0.00030.00030.00030.20350.7841during proton therapy [13, 14]. Taking into account their results, theuse of a hydrogel spacer for proton therapy is highly recommended. In
addition, CK showed large dose reduction because it is conventionallyused for SBRT, which shows higher dose gradient in the target boundary than conventional radiotherapy. However, although we investigated
the techniques in a clinical setting, some facility uses VMAT and HT
combined with SBRT, and they were not evaluated in this study.
Third, our results showed no correlations between the rectal dose
reduction rate and CTV for all irradiation techniques. The reason isthat the rectal dose reduction rate depends on the complexity of the
shape of the hydrogel spacer rather than the size of CTV. However,
only the prostate was defined as CTV in this study; therefore, therelationship of the rectal dose reduction rate with the prostate cancer
staging is beyond the scope of this investigation, and a further study isneeded.
The effectiveness of using hydrogel spacer could depend on the sizeof the PTV margin. In this study, the rectal dose reduction with SO
was evaluated by using the clinical margin setting for all technologies.

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M. Saito et al.
Table 5. Spearman’s rank correlation coefficient between the rectal dose reduction
rate and CTV volume
Spearman’s rank correlation coefficient

3DCRT
VMAT
HT
CK
Proton

D80%

D50%

D20%

D2%

0.02860.10080.00450.0090−0.2248−0.0827−0.04810.0301−0.0632−0.1669

0.1519−0.2030−0.1940−0.3182−0.2977

0.4256−0.14890.13080.46620.0496

Fig. 4. Rectal dose reduction rate using hydrogel spacer in fivetechniques in 20 patients (average and standard deviation).

Fig. 3. Typical dose distribution of SO(−) and SO(+) and theresults of five modalities: (a) 3DCRT, (b) VMAT, (c) HT, (d)CK and (e) proton. The contour of the orange color illustrates
the rectum.

However, the size of the PTV margin for prostate radiotherapy could
be different between institutions depending on the irradiation technology and presence of image-guided radiotherapy. Therefore, our results
could vary depending on the size of the PTV margin, especially theposterior directional expansion. In addition, the rectal dose reduction
rate was thought to be defined by the relationship between the PTV
margin size and the shape of the hydrogel spacer. Furthermore, by comparing conventional treatment and SBRT, the latter is likely to benefit
from hydrogel spacer because of the steep dose gradient. Further study

is required to evaluate the effect of different margin sizes for the same
irradiation technique.
This work has some limitations. First, the pre- and post-CT images
differed slightly from each other because of the bladder volume change
at the time of implementation and the displacement of the rectum
due to the placement of the hydrogel spacer. Second, some cases were
not suitable for bladder dose constraints because the bladder volume
was smaller than the one in the clinical situation, while the dose was
reduced as much as possible by planners. Third, dose prescription anddose constraints varied among irradiation techniques. Additionally,
the beam arrangement of each technique was constant, which might
affect the results. However, this condition is often used clinically in ourfacilities; thus, it is important to show the benefit of the hydrogel spacer
in such conditions.

CONCLUSION
The results of this study demonstrated that all external radiotherapy
modalities with hydrogel spacer could reduce the rectal dose. The
3DCRT with hydrogel spacer would reduce medical costs by replacing
conventional VMAT without spacer for prostate cancer treatment fromthe point of view of the rectal dose. For high-dose gradient regions,

Rectal dose reduction with a hydrogel spacer
proton therapy and SBRT with CK show larger rectal dose reduction
than other techniques.

CONFLICT OF INTEREST
None declared.
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