Dosimetric study of line scanning for prostate cancer in comparison with passive scattering and volumetric modulated arc therapy

doi:10.21203/rs.3.rs-3401750/v1

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Research Article

Dosimetric study of line scanning for prostate cancer in comparison with passive scattering and volumetric modulated arc therapy

https://doi.org/10.21203/rs.3.rs-3401750/v1

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Purpose

We performed a planning study to compare the dose distribution of the line scanning (LS) method with that of passive scattering (PS) method and volumetric modulated arc therapy (VMAT) for patients with localized prostate cancer.

Methods

Thirty patients treated in 2017–2019 were randomly selected. The dose constraints were the clinical target volume (CTV) D98 ≥ 73.0 Gy (RBE), rectal wall V65 < 17% and V40 < 35%, and bladder wall V65 < 25% and V40 < 50%. The CTV doses and rectal and bladder wall dose volumes were calculated and evaluated using the Freidman test. P < 0.05 was determined to be statistically significant.

Results

In all patients, the LS technique satisfied the dose restrictions for the CTV, rectal wall, and bladder wall. Ten (33.3%) and 21 (70.0%) patients using the PS method and five (16.7%) and one (3.3%) patients using the VMAT, respectively, failed to meet the requirements for the rectal and bladder walls. Wide ranges of the rectal and bladder wall volumes of V10–V70 were lower with LS than with PS and VMAT. LS was superior to VMAT in all dose-volume rectal and bladder wall indexes. PS outperformed the other two methods at Dmax.

Conclusion

Compared with PS and VMAT, the LS method enables further reduction of the rectal and bladder doses while maintaining the CTV dose. Our results suggest that proton therapy for patients with localized prostate cancer could lower gastrointestinal and genitourinary toxicities by changing from PS to LS.

Radiotherapy is one of the radical treatments for patients with localized prostate cancer.[1, 2] To achieve both high curability and low rates of toxicities, it is essential to concentrate the dose to the target volume and reduce the dose to surrounding organs at risk (OARs). High-dose irradiation using intensity-modulated radiation therapy (IMRT) is currently considered one of the standard radiotherapies for prostate cancer.[3]

Given the physical characteristics of the Bragg peak, proton therapy can, in principle, better reduce the dose to OARs than the X-ray-based technique.[4] Proton therapy has been used to treat localized prostate cancer for the past 20 years. Recently, several studies have reported proton therapy results for localized prostate cancer, all of which showed favorable biochemical control and low rates of late gastrointestinal (GI) and genitourinary (GU) toxicities.[5–9] It is significant to note, however, that these results were all obtained with the technique of passive scattering (PS).

The current proton therapy technology is gradually shifting from PS to pensile beam scanning (PBS) methods that were developed to achieve a more efficient dose delivery of protons.[10] The PBS are new proton irradiation methods that have rapidly been adopted worldwide. Proton therapy's fundamental concept was proposed in the 1940s.[11] The first clinical proton therapy system was introduced in the 1990s in a hospital.[12] The PS technique was used in the early facilities to provide proton treatment. The technical foundation for the PBS method, a novel proton irradiation technique, was developed in the 1980s.[13] The PBS method was used for the first time in Japan in the 2010s and is currently available throughout many continents, including Europe and the US.[14] As of 2023, 11 of 19 facilities in Japan have started to perform proton therapy using the scanning method.

In theory, the PBS method, including line scanning (LS), can provide more localized dose distribution than the PS method, which is expected to improve prostate cancer treatment outcomes. However, due to the indolent nature of prostate cancer, the long-term outcomes of the PBS method have not yet been established. In addition, comparative studies of treatment plans involving either the scanning method or the PS method are limited.

In this study, we conducted a comparative study of the treatment plans based on the hypothesis that the LS method for localized prostate cancer would reduce the dose to the rectum and bladder compared with the PS method and the volumetric modulated arc therapy (VMAT).

Patients

Thirty patients who received proton therapy between January 2017 and March 2019 were selected at random. This study followed the standards of the Helsinki Statement and the current ethical guidelines and was approved by the XXXX Institutional Review Board (R030221). All patients were informed about the study and provided written consent forms.

Computed tomography (CT) simulation and contouring

CT imaging was performed using a SOMATOM Perspective CT Scanner(SIEMENS、Munich、Germany), with each patient in the spine position with a full bladder. After CT and magnetic resonance images were superimposed, contouring of the clinical target volume (CTV) and OARs were performed. The CTV was defined as the entire prostate and part or all seminal vesicles depending on the risk classification. The 3 mm inner volumes of the entire bladder and the rectum within 10 mm in the SI direction of the CTV were defined as the bladder and rectal wall, respectively, and were used for evaluation in this study.

Dose constraints

The prescribed dose for the CTV was standardized to 76.0 Gy or Gy (RBE [relative biological effectiveness]) in 38 fractionations. The RBE for proton therapy was defined as 1.1 for Co-60. The dose constraint was the same for all three treatments and was stipulated as follows: 1) CTV: D50 ≥ 76.0 Gy (RBE), D98 ≥ 73.0Gy (RBE), 2) rectal wall: V65 < 17%, V40 < 35%, 3) bladder wall: V65 < 25%, V40 < 50%. Dx is defined as the dose received by x % of the organ volume. Vx is defined as the relative volume of the organ that received at least x Gy or Gy (RBE).

In cases where the CTV dose constraints could be obtained, the dose to the OARs was reduced. Our hospital started proton therapy using the wobbler method in 2016; we changed to the scanning method in 2017. The definitions of contouring and dose constraints used in this study were those applied in the actual treatment of patients.

Treatment equipment

The proton therapy system used (Sumitomo Heavy Industries, Ltd., Tokyo, Japan), which has an energy range of 70–230 MeV, was equipped with a universal nozzle that can switch between the PS and LS methods. Truebeam STx (Varian Medical Systems, Palo Alto, CA) was used for the VMAT treatment. All three treatment plans were generated using Version 13.7 of Eclipse (Varian Medical Systems, Palo Alto, CA).

LS method

The LS method is one of the scanning methods used in proton therapy.[15] The equivalent depth of water from the body surface to the target in the direction of the treatment beam is calculated, and then the deepest slice is swept with the optimal proton energy. Subsequently, the proton energy is changed, and the dose is delivered to a shallower slice of it. These steps are repeated for all of the target cross-sections to form a spread-out Bragg peak (SOBP).[16]

Along with spot scanning and raster scanning, the LS method is one of the PBS techniques.[17] These three methods differ in scan time, which may cause clinical problems in tumors with respiratory movement.[18] However, prostate cancer does not require consideration of the respiratory motion. We conducted this analysis with the assumption that the dose distribution of the LS technique might be representative of PBS.

The most crucial characteristic of proton beams is that they stop where they are supposed to, unlike penetrating X-rays. This characteristic, meanwhile, also adds to the uncertainty. Thus, range uncertainty must be considered in the treatment planning of proton therapy, particularly for the PBS method.[19] In this research, the LS method of treatment planning is based on robust optimization, which takes into account the movement of CTV and the range uncertainty of the proton beam. it produces a dose distribution that takes into account the internal and set-up margins, virtually the same as PTV.[20, 21]

The treatment plan used two beams with gantry angles of 90° and 270°, with the isocenter set in the center of the CTV. A pencil beam algorithm was used with a 2.5 × 2.5 × 2.5 mm dose grid for the proton dose calculation. Finally, for the obtained beam information, dose calculations were performed for a total of 12 different displacements of ± 5 mm (3 mm on the rectal side) relative to the isocenter and ± 3.5% uncertainty in the CT values and stopping-power-ratio conversion to evaluate the CTV dose.

PS method

The PS proton beam was irradiated from the cyclotron accelerator and then expanded to the required SOBP using beam-wobbling magnets, a lead scatterer, and ridge filters. Compensators were designed and applied to adjust the distal shape of the SOBPs according to the target locations and direction of the beams.

The PS beams were centered on the PTV with gantry angles = 90° and 270°. Setup errors of 5 mm were assigned to the CTV, similar to the definition of the PTV. A beam-specific PTV (bs-PTV) was created and planned using a CT value, an uncertainty of ± 3.5% in the stopping-power-ratio conversion, and smearing margins of 6 mm.[22, 23] The irradiation field was designed using multileaf collimators (MLCs) with a field margin of 10 to 12 mm according to the shape of the bs-PTV. Dose calculations were performed using the pencil beam algorithm with a 2.5 × 2.5 × 2.5 mm dose grid. In the latter eight fractions of PS therapy, the cone-down technique was used to reduce the dose to the rectum. The aggregated dose results from the initial and boost irradiation fields are reported using the PS method.

VMAT

VMAT (RapidArc, Eclipse Treatment Planning System version 13, Varian) is an advanced form of IMRT. VMAT uses one or more arcs that simultaneously vary the gantry rotation speed, dose rate, and leaf position of the MLC to deliver a highly conformal radiation dose to the target.[24]

Two coplanar arcs with a 10 MV X-ray were used in this study. The PTV was set to be 5 mm margin from CTV, with a margin of 3 mm to that of the posterior. This was based on the assumption that image guidance would be done using cone-beam CT, and a smaller margin was used than that used in several clinical trials. Dose optimization was performed using the photon optimizer 13.7 of the Eclipse treatment planning system. The dose calculation algorithm was AcurosXB with the calculation grid of 2.5 × 2.5 × 2.5 mm.

Treatment plan comparison and statistical analysis

Unlike PS and VMAT, LS does not have the concept of a PTV. LS, however, involves both setup errors and beam uncertainties in its planning and evaluation process. Hence, we consider them similar, although the three treatment planning methods do not use the same evaluation set. Accordingly, in this study, the CTV was used for dose analysis of the target volume. D98, D50, D02, Dmax, and the heterogeneity index (HI) were compared as indices of the CTV. HI is calculated as follows; (D02 - D98)/D50. For rectal and bladder walls, the evaluation indices were every 10 Gy for V10 to V60, and every 5 Gy for V65 to V75, Dmean, and Dmax, respectively. All parameters above were evaluated using the Friedman test followed by adjustment using the Bonferroni method, with P < 0.05 considered to be statistically significant. Statistical analysis was performed using SPSS version 22.0 (IBM, Armonk, NY, USA).

The clinical characteristics of 30 patients analyzed in this study are shown in Table 1. A comparison of the dose distribution between the three treatment modalities for a representative example case is shown in Fig. 1. Figure 2 shows the DVH curves for each patient and the median values in the CTV (a), rectal wall (b) and bladder wall (c), respectively, which are summarized in Table 2.

Table 1

Patient characteristics
Variable	Level	N	%
Number		30	100
T classification	T1	14	46.7
	T2	12	40.0
	T3	4	13.3
Gleason score	6	6	20.0
	7	12	40.0
	8–10	12	40.0
NCCN Risk group	Low	5	16.7
	Intermediate	10	33.3
	High	10	33.3
	Very High	5	16.7
ADT	Yes	15	50.0
	No	15	50.0
Variable		Median	Range
Age (year)		70.5	59–86
iPSA (ng/ml)		8.3	4.1–116.1
Positive core (%)		25	5.3–100
ADT period (month)		30	4–112
CTV volume (cm³)		32.2	17.8–117.5
Rectal wall volume (cm³)		21.4	16.1–31.0
Bladder wall volume (cm³)		38.8	24.8–62.6
Abbreviations: NCCN, National Comprehensive Cancer Network; ADT, androgen deprivation therapy; PSA, prostate-specific antigen; CTV, clinical target volume

Table 2

Comparison of the dosimetric parameters of CTV, rectal wall and bladder wall for the LS, PS and VMAT plans.
Structure	Dose metric	LS	PS	VMAT	P
CTV	D98 {Gy (RBE), median (range)}	74.9 (73.9–75.3)	75.0 (73.3–76.0)	74.2 (73.0–77.1)	a) 1.000 b) < 0.001 c) < 0.001
	D50 {Gy (RBE), median (range)}	76.0 (75.9–76.0)	76.0 (75.3–77.1)	75.9 (75.4–76.5)	0.393
	D02 {Gy (RBE), median (range)}	77.3 (76.6–78.5)	77.1 (76.4–79.3)	77.8 (76.5–78.7)	a) 1.000 b) 0.009 c) 0.014
	Dmax {Gy (RBE), median (range)}	79.3 (77.5–82.0)	77.7 (76.7–80.6)	79.5 (77.8–81.0)	a) < 0.001 b) 1.000 c) < 0.001
	Heterogenity index {median (range)}	0.029 (0.018–0.049)	0.028 (0.019–0.048)	0.072 (0.047–0.097)	a) 0.905 b) < 0.001 c) < 0.001
Rectal wall	V10 {%, median (range)}	37.1 (23.2–46.3)	52.0 (31.7–73.5)	70.1 (63.9–87.2)	a) < 0.001 b) < 0.001 c) 0.060
	V20 {%, median (range)}	29.5 (18.6–36.3)	41.5 (26.2–60.8)	49.3 (40.3–80.8)	a) < 0.001 b) < 0.001 c) 0.014
	V30 {%, median (range)}	24.4 (15.5–30.5)	35.5 (22.3–50.7)	35.3 (24.2–66.4)	a) < 0.001 b) < 0.001 c) 1.000
	V40 {%, median (range)}	20.4 (13.0–26.1)	29.2 (18.6–44.1)	26.2 (16.2–51.9)	a) < 0.001 b) < 0.001 c) 0.014
	V50 {%, median (range)}	16.9 (10.6–22.0)	24.3 (14.6–37.4)	20.2 (9.5–41.6)	a) < 0.001 b) < 0.001 c) 0.001
	V60 {%, median (range)}	13.1 (8.1–17.8)	18.4 (10.6–29.0)	15.1 (6.1–35.4)	a) < 0.001 b) < 0.001 c) < 0.001
	V65 {%, median (range)}	10.6 (6.5–15.5)	15.0 (8.0–25.4)	12.7 (4.9–32.2)	a) < 0.001 b) 0.085 c) 0.002
	V70 {%, median (range)}	7.9 (4.1–12.5)	10.1 (4.2–21.2)	10.1 (3.6–28.5)	a) 0.014 b) < 0.001 c) 0.590
	V75 {%, median (range)}	1.7 (0.2–7.7)	0.8 (0–12.2)	3.4 (0.5–16.0)	a) 0.006 b) 0.736 c) < 0.001
	Dmax {Gy (RBE), median (range)}	77.2 (75.5–79.2)	75.9 (74.3–78.0)	77.8 (76.8–79.5)	a) 0.002 b) 0.072 c) < 0.001
	Dmean {Gy (RBE), median (range)}	17.6 (11.2–22.2)	24.4 (15.5–34.1)	27.5 (21.9–44.1)	a) < 0.001 b) < 0.001 c) 0.014
Bladder wall	V10 {%, median (range)}	40.8 (24.5–57.0)	54.4 (35.3–73.4)	60.8 (41.6–84.9)	a) < 0.001 b) < 0.001 c) 0.060
	V20 {%, median (range)}	34.7 (20.5–47.2)	47.5 (31.9–64.7)	50.5 (35.1–66.5)	a) < 0.001 b) < 0.001 c) 0.590
	V30 {%, median (range)}	30.6 (17.7–42.5)	43.0 (29.2–58.2)	42.0 (27.0–52.4)	a) < 0.001 b) < 0.001 c) 0.117
	V40 {%, median (range)}	26.7 (15.3–36.7)	39.3 (26.7–52.3)	32.8 (20.7–41.3)	a) < 0.001 b) < 0.001 c) 0.001
	V50 {%, median (range)}	23.5 (13.1–32.4)	35.3 (23.9–46.8)	26.0 (16.5–35.3)	a) < 0.001 b) < 0.001 c) 0.001
	V60 {%, median (range)}	20.2 (10.8–28.2)	30.8 (20.9–40.8)	21.7 (13.5–30.1)	a) < 0.001 b) < 0.001 c) 0.001
	V65 {%, median (range)}	18.4 (9.5–24.8)	28.3 (18.9–38.0)	19.7 (12.2–27.4)	a) 0.001 b) < 0.001 c) 0.001
	V70 {%, median (range)}	15.9 (8.0–20.3)	24.0 (15.7–33.8)	17.4 (10.8–24.4)	a) 0.001 b) < 0.001 c) 0.001
	V75 {%, median (range)}	9.3 (0.1–14.0)	11.6 (2.1–26.4)	12.1 (4.7–16.6)	a) < 0.001 b) < 0.001 c) 1.000
	Dmax {Gy (RBE), median (range)}	78.1 (76.5–79.4)	76.8 (75.9–78.8)	79.0 (77.4–79.6)	a) 0.014 b) < 0.001 c) 0.004
	Dmean {Gy (RBE), median (range)}	21.8 (12.8–29.2)	31.0 (20.7–41.0)	30.0 (20.0–37.6)	a) < 0.001 b) < 0.001 c) 0.590
Abbreviations: CTV, clinical target volume; LS, line scanning; PS, passive scattering; VMAT, volumetric modulated arc therapy; Dx, dose received by x % of the organ volume; Dmax, maximum dose; Vx, the relative volume of the organ that received at least x Gy or Gy (RBE); Dmean, mean dose; RBE, relative biological effectiveness.
a) Comparison between LS and PS, b) comparison between LS and VMAT, c) comparison between PS and VMAT.

In all 30 patients that were investigated, the LS technique satisfied the dose restrictions for the CTV, rectal wall, and bladder wall. The PS technique failed to fulfill the criteria in 10 (33.3%) and 21 patients (70.0%) in the rectal wall (9 patients in V65 and V40, 1 in V65) and bladder wall (18 patients in V65 and V40, 3 in V65), while meeting the CTV criteria. Although all the patients satisfied the requirements for CTV using the VMAT method, while 5 patients (16.7%) in rectal wall (2 patients in V65 and V40, 3 in V65), and 1 patient (3.3%) in the bladder wall (V65) failed meet the dose constraints.

CTV

All three treatments showed similar dose coverage of the CTV, although the overall index values in the LS and PS were slightly more favorable than those in the VMAT. PS was better than LS only in terms of Dmax.

Rectal wall

Figure 3a is the box-and-whisker plots that summarize the results of the rectal wall. LS reduced rectal wall dose in the range of V10-V70 and Dmean with statistical significance over the other two methods. For V65, LS showed a dose decrease of 4.4% compared to PS and 2.1% to VMAT cases. For V40, the corresponding values were 8.8% and 5.8%, respectively.

PS was the best among the three methods in the high dose range (V75, Dmax). There was no dose-volume index for which VMAT was better than LS. Comparing PS and VMAT, PS reduced the dose in the low (V10-V20) and high dose regions (V75, Dmax), while VMAT reduced the dose in the medium-dose region (V30-V65).

Bladder wall

LS was the best for all indices except Dmax in the bladder wall (Fig. 3b). LS showed a median drop of 9.9% and 1.3% compared to PS and VMAT in V65 of the bladder wall. For V40, the corresponding values were 12.6% and 6.1%, respectively.

As observed in the rectal wall, LS outperformed VMAT in all indicators. Only at Dmax, PS showed a lower dose than LS and VMAT. VMAT yielded a lower irradiated volume in the medium- to high-dose range (V30 to V70) compared to PS.

This is the first study to simultaneously compare the LS, PS, and VMAT treatment plans for localized prostate cancer. The LS technique was successful in all of the patients examined, even though the rectum and bladder constraints in this study were stricter than those typically used in clinical trials.[25, 26] According to the study's findings, switching from PS proton therapy to LS for localized prostate cancer could further reduce side effects while keeping the treatment's effectiveness.

Rectal dose and GI toxicities

According to the findings of this study, rectal bleeding after the LS method is expected to be comparable to that after the PS method and better than that following the VMAT. Several studies have reported that late rectal bleeding results from an irradiated rectal volume with a high dose range (from > 60 Gy to Dmax).[27, 28] Colaco et al. analyzed 1285 patients treated with proton therapy and reported that V75 was a prognostic factor.[29] Their results showed that rectal wall V75 < 9.2% was associated with significantly less rectal bleeding of grade 2 or higher. In the 30 patients, we analyzed in this study, all patients fulfilled this V75 criterion in LS, with the highest case representing only 7.7%. The median index of LS was inferior to PS in V75 and Dmax in this study, although the difference was slight (0.9% and 1.3 GyE).

Along with reducing rectal bleeding, LS proton therapy also could improve other GI toxicities. The findings of several studies suggest a necessity for overall dose reduction, not only in the high-dose range but also in the low- to the medium-dose range to minimize late GI toxicities. A recent study revealed that other GI symptoms, such as fecal incontinence, bowel frequency, rectal pain, and rectal ulceration, are associated with low- to medium-dose ranges.[30] Among these symptoms, fecal incontinence has been reported to be highly influenced by V30-V40.[31, 32]

The use of perirectal hydrogel spacer (SpaceOAR; Augmenix, Waltham, MA) in conjunction with scanning proton therapy will lessen overall GI toxicity as well as rectal bleeding. SpaceOAR is a bioabsorbable hydrogel which is inserted between the rectum and prostate before radiation therapy to create a temporary anatomic separation.[33] This device reduced the incidence of rectal bleeding following IMRT for prostate cancer in a phase 3 trial.[34] Additionally, a recent study showed that using hydrogel spacers during proton therapy can reduce rectal bleeding.[35] Combining dose reduction in the medium to low dosage range by the scanning method with dose reduction in the high dose range by spacer placement could result in a safer dose escalation.

Bladder, ureteral dose and GU toxicities

Our results revealed a general dose reduction in the bladder wall using LS compared to the other two methods. However, it is currently not clear to what extent these results will improve clinical GU toxicities. To summarize the results of previous studies, late GU toxicities do not correlate as clearly with DVH parameters as late GI toxicities.[36, 37] Multiple factors might impede the explanation for the correlation between DVH parameters and late GU toxicities. Unlike late GI symptoms, GU symptoms require a longer time to develop over several years.[5, 6] Even without radiation therapy, aging increases the number of patients who experience GU symptoms.[38] In addition, a remaining major problem is that late GU toxicities are symptoms caused by both an irradiated bladder and urethra, and it is essentially difficult to identify which organ is the primary contributor.[37] Here, the impacts of irradiation on the bladder and urethra on GU toxicities are discussed individually.

It is expected that implementing the LS technique will lead to a reduction in GU toxicities through decreased bladder dose. Multiple studies have demonstrated an association between bladder dose and GU toxicities, along with various clinical variables.[39, 37] According to the available research, dose reduction is necessary for the entire bladder as well as the bladder triangle.[40, 41] The problem is that the bladder fluctuates during treatment and that the irradiated dose may differ from the planned dose.[42] However, based on the evidence presented, bladder dose reduction is likely to alleviate GU toxicities partially.

On the other hand, the effectiveness and technical feasibility of reducing the dose to the urethra, which is another source of GU toxicities, remain highly debated. Clinical trials using stereotactic body radiotherapy have revealed a relationship between urethral dose and early and late GU toxicities.[43, 44] However, compared to traditional whole prostate irradiation, a prospective clinical trial designed to reduce the urethral dose and improve GU side effects revealed worse biochemical control.[45] In addition, routine urethral dosage reduction also faces numerous technical difficulties.[46] Reducing the dose in the urethra, located approximately in the middle of the prostate, is more challenging than a partial dose reduction in the bladder. This idea is supported by evidence that a study using IMRT reported a substantial decrease in late GU toxicities.[47] In conclusion, we suggest that reducing the dose to the bladder rather than the urethra may be a more practical approach to alleviating GU toxicities.

Comparison of proton therapy and IMRT

The results of this study revealed that all dose-volume indices in VMAT were inferior to LS and partially better than PS. Currently, IMRT is one of the standard radiotherapies for patients with localized prostate cancer. VMAT is an advanced form of IMRT, and its main feature is the ability to shorten the time of treatment. Furthermore, some studies have demonstrated that VMAT improves the dose distribution compared to that of IMRT.[48] Proton therapy using PS has been reported to offer favorable disease control and low late GI and GU toxicity rates in several studies, although a direct comparison of the PS method with IMRT has not been reported at this time.[5–9]

Based on our findings, it is not inconsistent if IMRT and proton therapy using the PS technique did not significantly differ in terms of overall GI and GU toxicities in several studies. The planning comparisons between PS and IMRT have revealed that dose reduction for OARs with proton therapy is mainly observed in the low- to the medium-dose range.[49–51] In terms of toxicities, several trials comparing proton therapy versus IMRT have reported conflicting results.[52–54] Vapiwala et al. recently published results of a multicenter, retrospective study of IMRT versus proton therapy using mild hypofractionation in 1850 patients with low and intermediate risk.[55] The incidence of severe late GI and GU toxicities was low and did not differ between the two groups. However, the details of IMRT (static or rotational) and proton therapy techniques (PS or scanning) were not available.

Tran and colleagues conducted a comparative study evaluating intensity-modulated proton therapy, VMAT, and 4π radiotherapy in 10 patients diagnosed with prostate cancer.[56] The results of their investigation suggest that the potential of proton therapy to reduce the radiation dosage in the bladder and rectum is limited to the high-dosage range. Their findings are in contrast to those of the current study, which could have been influenced by factors such as the scanning beam's spot size and the gantry angle selected for the treatment.

Comparison of LS method and PS method

In the current study, significant dose reduction in the rectal and bladder walls was observed with LS compared to PS, which is expected to reduce clinical toxicities. However, contrary to our results, the PC001-09 study reported no difference in late GU toxicities at 12 months between the scanning and PS methods.[56, 57] In addition, regarding GI toxicities, the scanning method was slightly inferior to the PS in 12 months. It is difficult to directly interpret the inferiority of the scanning method is inferior based on the results of this study alone since the published results do not provide the patient background including comorbidities and pretreatment GU symptoms. The scanning method is a novel proton irradiation method, with few reports of efficacy and toxicity in prostate cancer. Future randomized control trials will need to confirm whether scanning with improved dose distribution reduces late GU and GI toxicities compared to IMRT and PS. In particular, long-term follow-up is necessary to evaluate late GU toxicities since the incidence of late GI toxicities reaches a plateau in the first 2–3 years after proton therapy, while the incidence of late GU toxicities tends to increase.[5, 6]

Limitation and strength

The most significant limitation of this study is that the target doses had to be compared in CTV because of the different conceptions of PTV in the three irradiation methods. However, the OAR doses for the three irradiation modalities were found to be significantly different even when the minimal needed CTV dose was met. Second, it is a planning study and did not compare the actual late toxicities. Considering the results of this study, we are currently preparing a prospective trial to compare the different clinical effectiveness of LS and PS in prostate cancer patients. Third, our study does not compare organs that affect sexual function and the costs of each treatment. However, the strength of our research is that it is the first study to compare the three treatments for prostate cancer in the same and a large number of patients.

The LS method can further reduce the dose to the rectal and bladder walls while maintaining the dose to the CTV compared to the PS method and VMAT, which may result in reduced late GI and GU toxicities.

Ethical Approval:

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. The study was approved by the Bioethics Committee of the Sapporo Teishinkai Hospital (R030221). All study participants received written information about the study and signed consent forms to participate and be published.

Competing interests: Not applicable

Authors' contributions:

All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Masaru Takagi, Yasuhiro Hasegawa and Kunihiko Tateoka. The first draft of the manuscript was written by Masaru Takagi and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Funding: Not applicable

Availability of data and materials: Research data are available at [https://data.mendeley.com/datasets/bbjj233tn7/draft?a=89aba735-0607-4077-8336-72c6d5b07ffa].

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Dosimetric study of line scanning for prostate cancer in comparison with passive scattering and volumetric modulated arc therapy

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Abstract

Purpose

Methods

Results

Conclusion

Figures

Introduction

Materials and methods

Patients

Computed tomography (CT) simulation and contouring

Dose constraints

Treatment equipment

LS method

PS method

VMAT

Treatment plan comparison and statistical analysis

Results

CTV

Rectal wall

Bladder wall

Discussion

Rectal dose and GI toxicities

Bladder, ureteral dose and GU toxicities

Comparison of proton therapy and IMRT

Comparison of LS method and PS method

Limitation and strength

Conclusion

Declarations

References

Additional Declarations

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