Reproducibility and stability of deep inspiration breath hold and free breath in breast radiotherapy based on real-time 3-dimensional optical surface imaging system

doi:10.21203/rs.3.rs-4962651/v1

Background

The aim of this study was to evaluate the inter-fraction reproducibility and intra-fraction stability of breast radiotherapy using deep-inspiration breath hold (DIBH) and free breathing (FB) based on an optical surface imaging system (OSIS).

Methods

Seventeen patients (510 breath-hold sessions) treated using a field-in-field (FiF) technique and twenty patients (600 breath-free sessions) treated with a volume-modulated arc therapy (VMAT) technique were included in this retrospective study. All the patients were positioned with the guidance of CBCT and OSIS, and also monitored with OSIS throughout the whole treatment session. Eight setup variations in three directions were extracted from the treatment reports of OSIS for all sessions and were subsequently manually introduced to treatment plans, resulting in a total of 296 perturbed plans. All perturbed plans were recalculated, and the dose volume histograms (DVH) for the target and organs at risk (OAR) were analyzed.

Results

The OSIS and CBCT for both DIBH and FB treatments showed a good agreement of less than 0.12 cm in each direction. The intra-fraction setup errors during DIBH were − 0.06 ± 0.07 cm, 0.12 ± 0.15 cm, and 0.12 ± 0.12 cm in the lateral, longitudinal, and vertical directions, respectively; for FB, the errors were − 0.02 ± 0.12 cm, 0.08 ± 0.18 cm, and 0.14 ± 0.20 cm, respectively. For the target, DIBH plans were more sensitive to positioning errors; the mean deviations in D₉₅ for CTV were 39.78 Gy-40.17 Gy for DIBH and 38.46 Gy-40.52 Gy for FB, respectively. For the OARs, the mean deviations—V₁₀, V₂₀, and D_mean to the heart; V₅, V₂₀, and D_mean to the ipsilateral lung; and D_mean to the breast—were lower for the FB plan compared with the DIBH plan.

Conclusion

SGRT can be an important tool for inter-fraction patient positioning and intra-fraction patient respiratory motion management in DIBH and FB breast cancer radiotherapy. The FB technology has greater possibility for the undercoverage of the target volume, while DIBH technology is more likely to result in increases in dose to organs at risk, especially the lung, heart, and breast. Furthermore, the tolerance of optical surface imaging systems could be reduced, indicating a potential method to reduce the dose delivery uncertainty caused by the patient’s respiratory motion.

Surface guided radiotherapy

Deep inspiration breath hold

Volumetric modulated arc therapy

Breast cancer

Breast cancer is one of the most common cancers in women worldwide. This is also reflected in China, where it accounted for 16.72% (306000) of all cancers in women in 2016 [1]. However, breast cancer has a high 5-year overall survival rate of 90% due to advances in prevention, early diagnosis, and multidisciplinary therapy. Radiotherapy (RT) is an integral part of the multidisciplinary management of breast cancer [2–5].

For left-sided breast cancer, deep inspiration breath hold (DIBH) techniques with field-in-field (FiF) strategy have become a standard method in radiotherapy modality [6–8]. FiF strategy refers to two open opposing tangential radiation fields with several segments (usually two to four) with a multileaf collimator (MLC) instead of wedges for improving target dose homogenization. Many studies have been published in recent years to demonstrate the advantages of DIBH radiotherapy in breast cancer treatments, showing a reduced irradiation dose for nearby organs at risk (OAR) and maintaining a better target dose coverage, due to an increased distance between the target and the heart [9–10]. Moreover, volumetric modulated arc therapy (VMAT) resulted in even better target coverage, sparing OARs for complex targets, such as concave-shaped breasts and breast cancer with supraclavicular lymph nodes metastasis [11, 12].

Patient positioning and respiratory movement are major concerns in dose delivery in FB and DIBH radiotherapy for breast cancer. This is because dose delivery deviation is mainly due to inaccuracy in patient positioning and patient respiratory movement throughout treatment, respectively. Regarding patient position, we can employ many additional imaging techniques, such as cone beam computed tomography (CBCT) and kilovoltage (kV) and megavoltage (MV) panel images to ensure accurate positioning. However, the disadvantages of such additional imaging are the associated extra radiation dose and the difficulty in monitoring patient respiratory motion for the whole treatment time. In recent years, optical surface imaging has provided the potential to monitor patient movement in real time during treatment and to help patients with pre-treatment positioning without the delivery of ionizing radiation [13,14]. Thus, surface-guided radiotherapy (SGRT) has been developed, which uses a 3-dimensional (3D) model of the skin surface for intrafraction patient positioning and monitoring for respiratory motion. The AlignRT system (Vision RT, London, UK) has been evaluated in this study.

To our knowledge, studies comparing FB and DIBH in breast radiotherapy using the SGRT technique are rare. Therefore, in this paper, we aimed to evaluate the following: (1) the inter-fraction clinical performance of pre-treatment positioning of the AlignRT system as compared with the XVI system; (2) the intra-fraction respiratory motion data acquired by SGRT in breast patients with FB and DIBH; (3) the dosimetric effect of intra-fraction respiratory motion acquired by SGRT in breast patients with FB and DIBH; (4) the stability of FB and DIBH in breast radiotherapy of intra-fractional motion.

Patient selection and contouring

Between February 2022 and October 2023, 17 patients with left-sided breast cancer treated with surface-guided DIBH and 20 patients with breast cancer treated by surface guided FB at the Department of Radiation Oncology, Sichuan Cancer Hospital, were recruited for the prospective study. This retrospective study was approved by the Ethics Committee of our hospital (Approval Number No. SCCHEC-02-2021-026). The mean age and median age were 57.6 ± 12.2 yrs and 55.2 yrs, respectively. Patient characteristics and radiotherapy parameters are summarized in Table 1.

Table 1 Patient characteristics and radiotherapy parameters of the study

Parameters	No. (%)
Age (yrs.)		Number of patients
mean ± SD	57.6 ± 12.2	DIBH	17 (45.9%)
median (range)	55.2 (50-68)	FB	20 (54.1%)
Tumors site		Nodal status
left	27 (73%)	pN0	26 (70.3%)
right	10 (27%)	pN1	9 (24.3%)
Tumor stage		pN2	1 (2.7%)
pT1	23 (62.2%)	pN3	1 (2.7%)
pT2	8 (21.6%)	Fractionation
pT3	5 (15.5%)	Hypo-fractionated (2.67 Gy/15 F)	17 (45.9%)
pT4	1 (2.7%)	Hypo-fractionated with simultaneously integrated boost (2.67 Gy and 3.2 Gy/15 F)	20 (54.1%)

The patients were immobilized with a WingStep (IT-V, Innsbruck, Austria) breast board in the supine position with their arms above their head. CT scans with a 3 mm slice thickness were acquired with a 16-slice Brilliance Big Bore CT (Philips Medical Systems, Cleveland, OH, USA). The CT scans were performed in free breathing (FB) and breath hold (BH) positions or with FB alone for their use in DIBH or FB treatment, respectively. After the CT scan, imaging datasets were imported to MIM Version 7.0.5 (MIM Software Inc.) for contouring. The CTVs and OARs (organ at risks) were delineated on each DIBH and FB scan by experienced radiation oncologists of the breast department. For the DIBH group, the clinical target volume (CTV_DIBH) encompassed the whole breast, excluding chest wall muscles, ribs, and pectoralis muscles, while for the FB group, CTV_FB encompassed the whole breast and supraclavicular fossa region, and gross tumor volume (GTV) included the tumor bed, visible surgical clips, and anatomical distortion. The planning target volume (PTV_FB and PTV_DIBH) was generated as an isotropic expansion of the CTV_FB and CTV_DIBH with a 3 mm margin in all directions, while PGTV was generated as an isotropic expansion of the GTV with a 5 mm margin in all directions. The OARs of this study were contoured on the CT image, which included the lung, heart, spinal cord, breast, liver, thyroid, esophagus, and trachea. Patients were treated either with hypo-fractionated therapy with simultaneously integrated boost (2.67 Gy for PTV_FB and 3.2 Gy for PGTV in 15 fraction) for FB or hypo-fractionated therapy for DIBH (2.67 Gy for PTV_DIBH in 15 fractions).

SGRT workflow

The AlignRT system (Vision RT, London, UK) employs a combination of light projectors, and the position of the patient is monitored with three cameras that generate a 3D map of the patient’s topography. Moreover, the system consists of software and a computer workstation, does not require the use of body film, and produces no irradiation during the imaging process. DIBH and FB patients were set up and monitored throughout treatment using AlignRT in real-time mode. In real-time mode, AlignRT displays three axis linear translations (vertical, lateral and longitudinal), the root mean square of the linear translations (RMS), and three axis rotations (yaw, pitch, and roll) (Fig. 1). The tolerance of linear translations and rotations is set to 3 mm and 3˚, respectively.

For both DIBH and FB treatments, the SGRT workflow consists of initial setup in the AlignRT system, and preparation before DIBH and FB treatment and daily treatment (Fig. 2). The workflow of DIBH is the same as that published by our group in other, previous studies [15,16]. First, for the DIBH and FB treatments, import the FB body contour into the Align RT workstation, delineate the surface-monitoring region for the initial setup position, and name it ‘FB Setup-DIBH’ or ‘FB Setup-FB’, respectively. Furthermore, for the DIBH treatment, we also need to import the DIBH body contour and plan into the Align RT workstation, delineate the surface monitoring region, and name it ‘DIBH Setup’. Second, the AlignRT and CBCT are used for daily patient setup and to assess the agreement of AlignRT with CBCT. Move the couch to align the laser lights and the three patient tattoo marks, and then adjust the couch to roughly position the treatment isocenter over the ipsilateral breast. Open the patient's FB Setup monitoring in the Align RT workstation. Based on the system prompt for errors, manually adjust the rotational direction by ≤ 3°, and then perform linear translation by ≤ 3 mm. For the DIBH treatment, switch to the DIBH Setup monitoring in the Align RT workstation. Instruct the patient to perform DIBH. Based on system prompts for errors, perform fine adjustments to the couch value. Third, acquire the CBCT images and record the deviations from the XVI workstation. Then, shift the couch based on CBCT registration and capture the present surface image as a reference image. Finally, turn on the gating switch in the Align RT workstation and activate the Elekta Response controller to monitor patient respiratory motion during beam delivery.

Fig. 3 shows the result of a typical breath-hold session with DIBH treatment and a free breath session with FB treatment, as tracked in the AlignRT system in a vertical direction and as printed from the system’s session reports, respectively. The shaded areas of Fig. 3 (A) indicate automatically gated beam hold when predetermined tolerance limits (± 3 mm) are exceeded.

Treatment planning

All clinical treatment plans were generated using Pinnacle TPS (version 9.10, Philips Radiation Oncology Systems, Fitchburg, WI, USA). Intensity modulation was performed using the direct machine parameter optimization (DMPO) algorithm. The collapsed cone (CC) algorithm was applied for final dose calculations, with a grid size of 3.0 mm. For the DIBH group, all plans used the tangential field-in-field (TFiF) technique, and treatments were performed with an Elekta Infinity linear accelerator (Elekta, Stockholm, Sweden) using 6 MV photons. Moreover, to be eligible for DIBH treatment, patients must be able to hold their breath for at least 25s and demonstrate a stable breath-hold position. The Infinity linear accelerator is equipped with a multileaf collimator, which has 40 leaf pairs of 0.5 cm thickness. The TFiF treatment plan consists of two opposing tangential fields with gantry angles between 300˚ and 315˚ for the medial beam and 120˚ and 135˚ for the lateral beam, with two or three sub-segments included. For the FB group, all plans had two arcs, with an angle ranging from 181˚ to 30˚ for the right-side breast cancer patients and from 330˚ to 179˚ for the left-side breast cancer patients, respectively. Eight setup variations were introduced for each reference DIBH and FB plan, shifting the isocenter from its reference position in the lateral, longitudinal, and vertical directions. The isocenter shifts in three directions with respect to the ±95% confidence interval of deviation distribution (mean±1.96*standard deviation) were acquired from the AlignRT system during beam-on time. A total of 296 perturbed plans (eight plans were generated per patient based on isocenter shifts values) were recalculated with these new isocenters and without changing any optimized parameters. Compared with the original plan, four groups of plans, DIBH_min, DIBH_max, FB_min and FB_max, were selected according to the maximum and minimum deviations of dosimetric parameters.

The dose constraints for the PTV were 1) D₉₅≥100% of the prescribed dose, and 2) D₂≤110% of the prescribed dose. For the OAR, both the DIBH and FB plans met the dose volume limits, as detailed in Table 2 [17]. For each DIBH and FB patient, two plans were created based on the AlignRT system: 1) a triple VAMT arc using FFF beams (FB_FFF) with collimator 0° and couch 0°, and 2) a triple VAMT arc using FF beams (FB_FF) with collimator 0° and couch 0°.

Table 2 Dose-volume constraints for OARs.

OARs	Dose volume parameters
Spinal cord	D_max<40 Gy
Ipsilateral lung	D_mean<15 Gy, V₂₀<30%, V₅<50%
Contralateral lung	V₅<20%
Heart (left-side breast cancer)	D_mean<15 Gy, V₅<50%
Heart (right-side breast cancer)	D_mean<15 Gy, V₅<50%
Liver	V₅<20%
Thyroid	D_mean<30 Gy

Evaluation of dosimetric data

The dosimetric quality of the treatments was measured using a dose-volume histogram (DVH). For CTV, the target coverage (D₉₅, D₉₈, D₉₉, D_mean, D₅₀,and D₂) and the conformity index (CI) were reported[18-20].

CI was defined as

CI=(TV_PV)²/(TV×PV) (1)

where PV is the volume covered by the prescription isodose. The CI values range between 0 and 1, and a CI close to 1 represents better conformity. Furthermore, dosimetric parameters were evaluated for the lung, heart, spinal cord, breast, liver, thyroid, esophagus, and trachea. The dose administered to the ipsilateral lung was evaluated using V₅, V₁₀, V₂₀, and the D_mean, and for the contralateral lung using V₅, V₁₀, and the D_mean; the D_max of the spinal cord was also recorded. For the heart, the V₅, V₁₀, V₂₀, and the D_mean were scored; D_max and D_mean for the esophagus; D_mean for the thyroid; D_mean for the trachea; and V₅ and D_mean for the liver. D_x represented the dose (in Gy) received by x% of the volume, V_y the volume (in percentage) receiving y Gy, D_max the maximum dose, and D_mean the mean dose.

Datasets were statistically analyzed using SPSS 19.0 software (IBM, New York, USA). The dosimetric parameters of the PTV and OARs were compared using the Wilcoxon Cox test. A p-value <0.05 indicates statistically significant differences.

Surface imaging system validation

In summary, we analyzed 255 treatment fractions and 510 breath-hold sessions during beam-on time, which included 12750 points with a one-second interval for DIBH treatment, and 300 treatment fractions and 600 breath-free sessions during beam-on time, which included 69000 points with a one-second interval for FB treatment. The mean treatment session times were 50 s and 230 s for DIBH and FB treatment, respectively. The setup errors (lateral, longitudinal, and vertical) across all patients and sessions during the CBCT session from the AlignRT system and XVI system for DIBH and FB treatments are shown in Table 3. For both treatments, the setup errors were below 0.22 cm. There were significant differences found in the vertical direction for FB and DIBH treatments (p<0.05), and no significant differences were found in other directions for FB and DIBH treatments (p>0.05). The setup deviations between AlignRT and XVI for DIBH treatment were 0.04 cm, 0.08 cm, and 0.02 cm in lat, lng, and vrt directions, respectively, and 0.06 cm, 0.08 cm, and 0.11 cm in lat, lng, and vrt directions for FB treatment, respectively.

Table 3 The difference of setup errors (mean ± standard) between the AlignRT system and XVI system for the DIBH and FB treatment during a CBCT session.

	DIBH (cm)			FB (cm)
Parameters	AlignRT	XVI	p	AlignRT	XVI	p
Lateral	-0.05±0.07	-0.01±0.02	>0.05	-0.05±0.16	0.11±0.17	>0.05
Longitudinal	0.11±0.07	0.03±0.02	>0.05	0.11±0.18	-0.19±0.12	>0.05
Vertical	0.22±0.10	0.20±0.14	<0.05	0.10±0.17	0.21±0.13	<0.05

Table 4 shows the result of inter-fraction respiratory motion at beam-on time in terms of mean, standard deviation and ±95%-confidence interval (CI) for DIBH and FB treatments, respectively. Overall, the mean changes for the maximum magnitude of the respiratory motion on the vertical axis were 0.12 ± 0.12 (±95%-confidence interval: [-0.12-0.36] cm) and 0.14 ± 0.20 (±95%-confidence interval: [-0.25-0.53] cm) cm for DIBH and FB treatment, respectively. Along the lateral and longitudinal axes, changes were quite similar: -0.06±0.07, 0.12±0.15, -0.02±0.06, and 0.08±0.08 mm for DIBH and FB treatments, respectively. Figure 4 shows histograms representing the differences between conventional patient positioning and the surface-based alignments for DIBH and FB treatment. More than 61.67% and 78.14% of the deviations were smaller than 2 mm in the lateral direction for DIBH and FB, respectively; more than 58.48% and 68.72% of the deviations were smaller than 2 mm in the longitudinal direction for DIBH and FB, respectively; and more than 63.76% and 75.35% of the deviations were smaller than 2 mm in the vertical direction for DIBH and FB, respectively.

Table 4 The inter-fraction respiratory motion data acquiring by SGRT for FB and DIBH treatment during a beam on time.

Treatment	Beam on time
	Lateral (cm)			Longitudinal (cm)			Vertical (cm)
	Mean ± SD	CI-95%	CI+95%	Mean ± SD	CI-95%	CI+95%	Mean ± SD	CI-95%	CI+95%
DIBH	-0.06±0.07	-0.20	0.07	0.12±0.15	-0.17	0.41	0.12±0.12	-0.12	0.36
FB	-0.02±0.12	-0.26	0.22	0.08±0.18	-0.27	0.43	0.14±0.20	-0.25	0.53

Target doses

The CTV dosimetric parameters (mean and standard) obtained for the DIBH and FB treatments are shown in Table 5 and Figure 5. The target coverage of the original plans was clinically acceptable for both techniques, with D₉₅ values of 40.1±1.36 Gy and 40.52±0.19 Gy for DIBH and VAMT treatments, respectively. For DIBH treatment, the dosimetric parameter differences in the DIBH_org plan compared with DIBH_min and DIBH_max plans were statistically significant (p<0.05). The mean absolute differences (DIBH_max-DIBH_min) ΔD₉₅, ΔD₉₈, ΔD₉₉, ΔD_mean, ΔD₂, ΔD_max, ΔD₅₀, and ΔCI were 0.39 Gy, 0.58 Gy, 1.0 Gy, 0.56 Gy, 1.33 Gy, 1.67 Gy, 0.77 Gy, and 0.12 Gy, respectively. For VAMT treatment, there was no significant difference in the D₉₈ and D₉₉ of the CTV between FB_org and FB_max plans (p>0.05), and the differences in other parameters were statistically significant (p<0.05). The mean absolute differences (FB_max-FB_min) ΔD₉₅, ΔD₉₈, ΔD₉₉, ΔD_mean, ΔD₂, ΔD_max, ΔD₅₀, and ΔCI were 2.3 Gy, 3.96 Gy, 4.41 Gy, 1.27 Gy, 2.12 Gy, 3.21 Gy, 1.11 Gy, and 0.07 Gy, respectively. The mean absolute differences in CTV between DIBH_min and DIBH_max and FB_min and FB_max are shown in Figure 6a. In Figure 6a, for the CTV, the absolute differences in the dosimetric parameters of DIBH treatment were lower than the FB treatment.

Table 5 Mean value and range of CTV dosimetric parameters absolute between the original and perturbed DIBH and FB treatments.

Volume

Parameters

DIBH

FB

DIBH_org

DIBH_min

DIBH_max

p value

FB_org

FB_min

FB_max

p value

p1

p2

p1

p2

CTV

D₉₅ (Gy)

40.10±1.36

39.78±0.86

40.17±0.79

<0.05

40.52±0.19

38.46±1.76

40.76±0.31

<0.05

D₉₈ (Gy)

39.10±1.06

38.59±1.36

39.17±1.09

<0.05

40.09±0.22

36.54±2.79

40.05±0.48

<0.05

0.795

D₉₉ (Gy)

38.37±1.26

37.50±2.03

38.50±1.28

<0.05

0.097

39.79±0.30

35.13±3.28

39.54±0.59

<0.05

0.173

D_mean (Gy)

42.42±0.14

42.26±0.19

42.82±0.31

<0.05

43.44±1.0

42.75±1.01

44.02±1.23

<0.05

D₂ (Gy)

43.69±0.15

43.98±0.40

45.31±0.72

<0.05

49.27±2.68

48.67±2.52

50.79±3.17

<0.05

D_max (Gy)

44.11±0.18

44.52±0.55

46.19±0.57

<0.05

50.54±2.77

49.90±2.66

53.11±3.67

<0.05

D₅₀ (Gy)

42.75±0.14

42.32±0.14

43.09±0.30

<0.05

42.43±0.86

41.95±0.95

43.06±1.07

<0.05

CI

0.67±0.07

0.49±0.09

0.61±0.06

<0.05

0.67±0.12

0.65±0.08

0.72±0.09

<0.05

OARs doses

OARs’ DVH dosimetric parameters (mean and range values), obtained for the original (DIBH_org and FB_org) and perturbed (DIBH_min, DIBH_max, FB_min and FB_max) DIBH and FB treatments, are shown in Table 6 and Figure 6. The mean absolute differences (DIBH_max-DIBH_min) ΔV₅, ΔV₁₀, ΔV₂₀ and ΔD_mean of the heart; ΔD_max of the spinal cord; ΔV₅, ΔV₁₀, ΔV₂₀ and ΔD_mean of the ipsilateral lung; ΔV₅, ΔV₁₀ and ΔD_mean of the contralateral lung; ΔD_mean of the breast; ΔD_meanof the thyroid; ΔD_mean of the trachea; and ΔD_max and ΔD_mean of the esophagus were 3.03 %, 8.64 %, 6.63%, 2.99 Gy, 0.1 Gy, 11.98%, 11.64%, 11.08 %, 4.23 Gy, 0.3 %, 0.13 %, 0.16 Gy, 2.02 Gy, 0.19 Gy, 0.23 Gy, 0.34 Gy, 0.18 Gy, 0.12 % and 0.13 Gy, respectively. The mean absolute differences (FB_max-FB_min) ΔV₅, ΔV₁₀, ΔV₂₀ and ΔD_mean of the heart; ΔD_max of the spinal cord; ΔV₅, ΔV₁₀, ΔV₂₀ and ΔD_mean of the ipsilateral lung; ΔV₅, ΔV₁₀ and ΔD_mean of the contralateral lung; ΔD_mean of the breast; ΔD_meanof the thyroid; ΔD_mean of the trachea; and ΔD_max and ΔD_mean of the esophagus were 11.65%, 5.39%, 1.52%, 1.48 Gy, 0.72 Gy, 10.69 %, 11.96%, 10.14 %, 3.45 Gy, 4.76% 1.39%, 0.4 Gy, 0.52 Gy, 0.52 Gy, 0.91 Gy, 1.71 Gy, 0.42 Gy, 5.38% and 0.94 Gy, respectively. The mean absolute differences in OARs between DIBH_min and DIBH_max and FB_minand FB_max are shown in Figure 7b. In Figure 6b, compared with DIBH treatment, the FB treatment provided a lower mean absolute difference V₁₀, V₂₀, and D_mean to the heart; V₅, V₂₀, and D_mean to the ipsilateral lung; and D_mean to the breast.

Table 6 Mean value and range of OARs dosimetric parameters absolute between the original and perturbed DIBH and FB treatments.

Volume

Parameters

DIBH

FB

DIBH_org

DIBH_min

DIBH_max

p value

FB_org

FB_min

FB_max

p value

p1

p2

p1

p2

Heart

V₅ (%)

4.86±2.92

1.83±1.77

4.86±2.92

<0.05

11.07±9.40

7.18±8.85

18.83±11.22

<0.05

V₁₀ (%)

2.75±1.94

0.71±1.05

9.35±5.93

<0.05

2.59±3.54

1.12±1.69

6.51±7.12

0.051

<0.05

V₂₀ (%)

1.56±1.29

0.30±0.63

6.93±4.95

<0.05

0.31±0.59

0.03±0.07

1.55±2.60

0.144

0.104

D_mean (Gy)

1.83±0.68

1.13±0.41

4.12±2.01

<0.05

2.63±0.91

2.17±0.07

3.65±1.55

<0.05

Spinal cord

D_max (Gy)

0.24±0.07

0.20±0.06

0.30±0.06

<0.05

2.82±1.84

2.57±1.70

3.29±2.03

<0.05

Ipsilateral lung

V₅ (%)

23.50±2.76

18.61±2.55

30.59±3.89

<0.05

33.46±5.66

28.72±5.16

39.41±6.37

<0.05

V₁₀ (%)

17.47±2.32

12.84±2.12

24.48±3.62

<0.05

19.40±5.77

14.14±4.64

26.10±7.02

<0.05

V₂₀ (%)

12.84±1.91

8.55±1.82

19.63±3.29

<0.05

6.97±4.28

3.0±2.62

13.14±6.68

<0.05

D_mean (Gy)

6.07±0.71

4.48±0.69

8.71±1.26

<0.05

6.08±1.53

4.80±1.08

8.25±2.26

<0.05

Contralateral lung

V₅ (%)

0.01±0.02

0±0

0.30±0.69

0.347

0.229

12.37±11.66

10.12±10.71

14.88±12.24

<0.05

V₁₀ (%)

0±0

0.13±0.31

0.145

0.260

1.82±2.66

1.19±1.90

2.58±3.40

0.085

<0.05

D_mean (Gy)

0.22±0.05

0.18±0.03

0.34±0.17

<0.05

2.28±0.96

2.11±0.93

2.51±1.01

<0.05

Breast

D_mean (Gy)

1.19±2.06

0.61±0.64

2.63±4.79

0.252

0.153

3.10±1.22

2.91±1.18

3.43±1.33

<0.05

Thyroid

D_mean (Gy)

0.29±0.13

0.22±0.11

0.41±0.20

<0.05

0.83±0.31

0.63±0.19

1.15±0.54

<0.05

Trachea

D_mean (Gy)

0.37±0.06

0.29±0.06

0.52±0.10

<0.05

2.22±1.51

1.79±1.26

2.70±1.79

<0.05

Esophagus

D_max (Gy)

0.54±0.09

0.44±0.05

0.78±0.20

<0.05

5.38±2.84

4.68±2.58

6.39±3.17

<0.05

D_mean (Gy)

0.44±0.09

0.26±0.05

0.44±0.09

<0.05

1.63±0.89

1.44±0.77

1.86±1.0

<0.05

Liver

V₅ (%)

0±0

0.12±0.23

0.231

0.160

7.30±5.33

5.17±3.95

10.55±7.30

<0.05

D_mean (Gy)

0.17±0.05

0.13±0.04

0.26±0.10

<0.05

1.65±0.90

1.30±0.68

2.24±1.29

<0.05

In recent years, radiotherapy techniques such as FB and DIBH have been used widely in the radiotherapy of breast cancer. The present study addresses the topic of FB and DIBH stability and reproducibility during surface-guided breast radiotherapy. Surface imaging can be used to monitor the chest wall position during DIBH and the FB. We report on intra-breath-hold and intra-free-breath stability and inter-fraction reproducibility during DIBH and FB radiotherapy in a breast cancer patient study (17 patients with 12750 points for DIBH and 20 patients with 69000 points for VMA) and using an Align RT system.

DIBH and FB techniques have different dosimetry advantages in the radiotherapy of breast cancer, respectively. However, in addition to dosimetry considerations, patient positioning and respiratory movement are major concerns for dose delivery in FB and DIBH radiotherapy for breast cancer. This requires patient positioning monitoring be maintained as accurately as possible during treatment to ensure that the dose is delivered as intended. Shah et al. analyzed 50 patients undergoing radiation therapy for whole breast; these patients were aligned daily using optical surface imaging, and shifts from skin marks were recorded, in comparison with MV port films [21]. Reitz et al. evaluated intra-breath-hold stability and inter-fraction breath-hold reproducibility in clinical practice [22].

Compared with general images from CBCT, SGRT (non-invasive and non-radiative) uses optical surface imaging to verify the position. Several studies have evaluated the setup accuracy of SGRT systems compared to CBCT [23–25]. In our study, CBCT was used to verify AlignRT system corrections, showing the stability gained when using SGRT for intra-fraction patient setup, where the setup error is similar to CBCT. Average setup differences between both AlignRT and CBCT were below 0.08 cm for DIBH treatment and below 0.11 cm for FB treatment, in three directions. This result is in agreement with previous studies [25, 26]. Alderliesten et al [25] also compared the AlignRT system to CBCT imaging setup errors for DIBH radiotherapy, and showed similar results. Batin et al. [26] demonstrated that positioning with AlignRT after laser alignment is more accurate than when only the laser is used. In Table 3, it can be observed that the setup errors from AlignRT were slightly larger than with the CBCT. This is because for the CBCT, the setup error was based on the target volume, but the AlignRT was based on the patient’s surface imaging. In addition, due to the different ROI position, AlignRT mainly looks at the ventral side of the breast, which can differ in shape during an optical imaging acquisition session. Thus, AlignRT has reliable patient positioning stability similar to CBCT and the potential to replace CBCT for positioning in breast cancer patients using FB and DIBH.

At present, analyses of dosimetry between DIBH and FB have been reported in many studies [27–29]. In addition to dosimetry comparisons, the impact of patient respiration on both techniques needs to be evaluated. Patient respiration can lead to an increase in dose delivery uncertainty, prompting the monitoring of treatment delivery to ensure that the target and OAR-delivered dose correspond to those planned. However, most prior studies did not report dosimetric deviation due to patient respiration during beam-on duration, but mainly focused on the three directions of motion of the patient [22, 23, 30]. Zhao et al. [15] compared the impact of positioning errors in FB and tangential field-in-field (TFiF) plans for breast treatments, but the positioning errors in the three directions were artificially set to 3, 5, and 10 mm, and not taken from the surface-guided system. In addition to the advantages provided with SGRT for setup positioning, the main advantage in the present study is the opportunity for real-time monitoring. In this study, firstly, patient respiratory data were acquired from AlignRT for DIBH and FB treatments; secondly, perturbations were introduced to the plans.

Intra-DIBH and intra-FB stability were both smallest in the vertical direction during beam-on time, as shown in Table 4. This may be due to patient respiration factors during beam-on time. The deviation values in the vertical direction averaged over all patients were 0.12 ± 0.12 cm for DIBH and 0.14 ± 0.20 cm for FB, respectively. The average value and standard deviation showed that the respiratory motion amplitude of FB technology is greater than DIBH. The reason for this situation is that patients use FB technology in a state of free breathing, and inhalation and exhalation have a positive and negative relationship in the AlignRT system, which leads to a greater average value. Our surface-based alignments specifically showed that across all patients, skin-mark alignments were poorer in the three directions (especially the deviation within the range from − 2 to 2 mm) for DIBH treatment in comparison with the FB treatment (Fig. 4). This result indicates that the stability of the FB treatment is better than the DIBH treatment of inter-fractional motion. This is because DIBH treatment has higher requirements for patients; patients must be able to hold their breath for at least 25 s and to replicate the breath retention setting five times in succession. One potential solution could involve increasing patient’s breath-holding training.

When perturbations were introduced to DIBH and FB plans, however, DIBH techniques guaranteed an accurate target coverage with deviations in the target DVH dosimetric, whereas FB plans seemed more sensitive to positioning errors, with mean deviations of 2.3 Gy and 3.96 Gy for D₉₅ and D₉₈, respectively. In Table 5 and Fig. 6(A), it is possible to observe that respiratory movement has a dosimetric impact on CTV that is larger for FB plans than for DIBH plans. Zhao et al. [15] also found such dosimetric effects. For breast cancer radiotherapy, dose sparing of the ipsilateral lung, contralateral breast, and heart are particularly important. For the OARs, DIBH plans appeared to be more sensitive to the positioning errors’ mean absolute difference (Plan_max-Plan_min) for V₁₀, V₂₀, and D_mean to the heart, V₅, V₂₀, and D_mean to the ipsilateral lung, and D_mean to the breast. In addition, the well-known second cancer risk for contralateral breast and lung forces us to monitor treatment delivery to ensure that the OAR-delivered dose corresponds to the planned one [32]. One possible solution is to increase the threshold in the optical surface imaging system, with beam delivery interruption if patients’ positions exceed their tolerance limits.

One limitation of this study is that the tolerance of linear translations and rotations are set to 3 mm and 3˚ in the AlignRT system. Xiao et al. [31] reported different values of variabilities (translation 1 mm and rotation 1˚), which resulted in small dosimetric consequences. Thus, a lower tolerance could assure DIBH and FB with good stability and low intra-fraction and inter-fraction variability, contributing to smaller deviations in dosimetric delivery. The three axis rotations from AlignRT were not discussed. Wiant et al. [32] showed that the mean rotations were all < 0.1˚ for thirty free-breathing breast patients. This indicates that rotation deviations might negligible in dosimetric delivery.

To conclude, due to the large amount of data analyzed, the optical real-time surface imaging system in the present study was demonstrated to be an important tool for inter-fraction patient positioning and intra-fraction patient respiratory motion management in DIBH and FB breast cancer radiotherapy. Regarding the reproducibility of DIBH and FB, the setup deviations between AlignRT and CBCT were both < 0.12 cm. As a measure of DIBH and FB stability, the mean deviations were both < 0.2 cm. The FB technology has greater possibility for the undercoverage of the target volume, while DIBH technology is more likely to result in increases in dose to organs at risk, especially the lung, heart, and breast. In addition, the tolerance of the optical surface imaging system could be reduced, and could then become a potential method for reducing the dose delivery uncertainty caused by patient respiratory motions.

Acknowledgements

None.

Conflict of interest statement

There is no conflict of interest to declare.

Author contributions

Design of the research: BT, JXW. Treatment plans: FW, FY. Statistical Analysis: OL, JL, KY, LPX. Manuscript preparation: FY, JXW. Manuscript writing: JXW. Manuscript final revision: BT, XLW. All authors contributed to the article and approved the submitted version.

Funding

This study was supported by Sichuan Natural Science Foundation Program (No. 2024NSFSC1878) and Sichuan Cancer Hospital Youth Project (No. YB2023025, No. YB2021032).

Availability of data and materials

The data are fully available without restriction in a public repository (Dryad). The reference treatment plans and corresponding perturbed plans were archived in the Informatic System of Sichuan Cancer Hospital.

Declarations

Ethics approval and consent to participate

This retrospective study was approved by the Ethics Committee of our hospital (Approval Number No. SCCHEC-02-2021-026).

Consent for publication

Not applicable.

Competing interests

None of the authors have any competing interests (financial and nonfinancial) in the manuscript.

Zheng RS, Zhang SW, Zeng HM, Wang SM, Sun K, Chen R, et al. Cancer incidence and mortality in China 2016. Journal of the national cancer center. 2022; 2(1): 1-9.
Offersen BV, Alsner J, Nielsen HM, et al. Hypofractionated Versus Standard Fractionated Radiotherapy in Patients with Early Breast Cancer or Ductal Carcinoma in Situ in a Randomized Phase III Trial: The DBCG HYPO Trial. Journal of Clinical Oncology. 2020; 38(31): 3615-3625.
Darby S, McGale P, Correa C, et al. Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: Meta-analysis of individual patient data for 10,801 women in 17 randomised trials. Lancet. 2011; 378: 1707-1716.
Brunt AM, Haviland JS, Wheatley DA, et al. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet. 2020; 395:1613-1626.
Trivedi SJ, Choudhary P, Lo Q, et al. Persistent reduction in global longitudinal strain in the longer term after radiation therapy in patients with breast cancer. Radiother Oncol. 2019; 132:148–54.
Hidekazu T, Shinya H, Hiroaki H. Determination of the optimal method for the field-in-field technique in breast tangential radiotherapy. J Radiat Res (Tokyo). 2014; 4 :769–73.
Krasin M, Mccall A, King S, Olson M, Emami B. Evaluation of a standard breast tangent technique: a dose-volume analysis of tangential irradiation using three-dimensional tools. Int J Radiat Oncol Biol Phys. 2000; 47(2):327–33.
Onal C, Sonmez A, Arslan G, Oymak E, Kotek A, Efe E, et al. Dosimetric comparison of the field-in-field technique and tangential wedged beams for breast irradiation. Jpn J Radiol. 2012; 30(3):218–26.
Duma M-N, Münch S, Oechsner M, Combs SE. Heart-sparing radiotherapy in patients with breast cancer: what are the techniques used in the clinical routine ?: A pattern of practice survey in the german-speaking countries. Med Dosim. 2017; 42(3):197–202.
Boda-Heggemann J, Knopf A-C, Simeonova-Chergou A, Wertz H, Stieler F, Jahnke A, et al. Deep inspiration breath hold-based radiation therapy: a clinical review. Int J Radiat Oncol Biol Phys. 2016; 94(3):478–92.
Donovan E, Bleakley N, Denholm E, Evans P, Gothard L, Hanson J, et al. Randomised trial of standard 2D radiotherapy (RT) versus intensity modulated radiotherapy (IMRT) in patients prescribed breast radiotherapy. Radiother Oncol. 2007; 82(3):254–64.
Ho AY, Mccormick B. A multicenter randomized trial of breast intensity-modulated radiation therapy to reduce acute radiation dermatitis. J Clin Oncol. 2009; 20(1):89–90.
Cho HL, Park ET, Kim JY, et al. Evaluation of radiotherapy setup accuracy for head and neck cancer using a 3‐D surface imaging system. J Instrumm. 2013; 8: T11002.
Cervino LI, Gupta S, Rose MA, Yashar C, Jiang SB. Using surface imaging and visual coaching to improve the reproducibility and stability of deep‐inspiration breath hold for left‐breast‐cancer radiotherapy. Phys Med Biol. 2009; 54:6853–6865.
Zhao YQ, Diao P, Zhang D, et al. Impact of positioning errors on the dosimetry of breath-hold-based volumetric arc modulated and tangential field-in-field left-sided breast treatments [J]. Front Oncol. 2020;10:554131.
Xin X, Li J, Zhao YQ, et al. Retrospective study on left-sided breast radiotherapy: dosimetric results and correlation with physical factors for free breathing and breath hold irradiation techniques [J]. Technol Cancer Res T. 2021; 20:1-8.
Taylor CW, Wang Z, Macaulay E, et al. Exposure of the heart in breast cancer radiation therapy: a systematic review of heart doses published during 2003 to 2013. Int J Radiat Oncol Biol Phys. 2015;93(4):845-853.
Audet C, Poffenbarger BA, Chang P, Jackson PS, Lundahl RE, Ryu SI, et al. Evaluation of volumetric modulated arc therapy for cranial radiosurgery using multiple noncoplanar arcs. Med Phys. 2011; 38(11):5863-5872.
Paddick I. A simple scoring ratio to index the conformity of radiosurgical treatment plans. J Neurosurg. 2000; 93(3):219-222.
Paddick I, Lippitz B. A simple dose gradient measurement tool to complement the conformity index. J Neurosurg. 2006; 123:194-201.
Shah AP, Dvorak T, Curry MS, et al. Clinical evaluation of interfractional variations for whole breast radiotherapy using 3-dimensional surface imaging. Pract Radiat Oncol. 2013; 3(1):16-25.
Reitz D, Walter F, Schönecker S, et al. Stability and reproducibility of 6013 deep inspiration breath-holds in left-sided breast cancer. Radiat Oncol. 2020; 15: 121.
Hamming VC, Visser C, Batin E, et al. Evaluation of a 3D surface imaging system for deep inspiration breath-hold patient positioning and intra-fraction monitoring. Radiat Oncol. 2019;14:125.
MacFarlane MJ, Jiang K, Mundis M, et al. Comparison of the dosimetric accuracy of proton breast treatment plans delivered with SGRT and CBCT setups. J Appl Clin Med Phys. 2021;00:1-6.
Alderliesten T, Sonke JJ, Betgen A, et al. Accuracy evaluation of a 3-dimensional surface imaging system for guidance in deep-inspiration breath-hold radiation therapy. Int J Radiat Oncol Biol Phys. 2013; 85:536–542.
Cravo Sá A, Fermento A, Neves D, et al. Radiotherapy setup displacements in breast cancer patients: 3D surface imaging experience. Rep Pract Oncol Radiother. 2018;23(1):61–67.
Loap P, Vu-Bezin J, Monceau V, et al. Dosimetric evaluation of the benefit of deep inspiration breath hold (DIBH) for locoregional irradiation of right breast cancer with volumetric modulated arctherapy (FB). Acta Oncologica. 2023; 62(2): 150–158.
Dumane VA, Saksornchai K, Zhou Y, et al. Reduction in low-dose to normal tissue with the addition of deep inspiration breath hold (DIBH) to volumetric modulated arc therapy (FB) in breast cancer patients with implant reconstruction receiving regional nodal irradiation. Radiat Oncol. 2018; 13:187.
Jin GH, Chen LX, Deng XW, et al. A comparative dosimetric study for treating left-sided breast cancer for small breast size using five different radiotherapy techniques: conventional tangential field, filed-in-filed, Tangential-IMRT, Multi-beam IMRT and FB. Radiat Oncol. 2013; 8: 89.
Reitz D, Carl H, Schönecker S, et al. Real-time intra-fraction motion management in breast cancer radiotherapy: analysis of 2028 treatment sessions. Radiat Oncol. 2018; 13: 128.
Xiao A, Crosby J, Malin M, et al. Single institution report of setup margins of voluntary deep-inspiration breath-hold (DIBH) whole breast radiotherapy implemented with real-time surface imaging. J Appl Clin Med Phys. 2018; 19:205–13.
Abo-Madyan Y, Aziz MH, Aly MMOM, et al. Second cancer risk after 3D-CRT, IMRT and FB for breast cancer. Radiother Oncol. 2014; 110(3): 471–6.

No competing interests reported.

Reproducibility and stability of deep inspiration breath hold and free breath in breast radiotherapy based on real-time 3-dimensional optical surface imaging system

Status:

Version 1

Abstract

Background

Methods

Results

Conclusion

Figures

Background

Methods

Results

Discussion

Conclusion

Declarations

References

Additional Declarations

Status:

Version 1