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A comparative study based on deformable image registration of the target volumes for external-beam partial breast irradiation defined using preoperative prone magnetic resonance imaging and postoperative prone computed tomography imaging

Radiation Oncology201914:38

https://doi.org/10.1186/s13014-019-1244-x

  • Received: 6 September 2018
  • Accepted: 25 February 2019
  • Published:

Abstract

Background

To explore the differences and correlations between the target volumes defined using preoperative prone diagnostic magnetic resonance imaging (MRI) and postoperative prone computed tomography (CT) simulation imaging based on deformable image registration (DIR) for external-beam partial breast irradiation (EB-PBI) after breast-conserving surgery (BCS).

Methods

Eighteen breast cancer patients suitable for EB-PBI were enrolled. Preoperative prone diagnostic MRI and postoperative prone CT scan sets for all the patients were acquired during free breathing. Target volumes and ipsilateral breast were all contoured by the same radiation oncologist. The gross tumor volume (GTV) delineated on the preoperative MRI images was denoted as the GTVpreMR and the tumor bed (TB) delineated on the postoperative prone CT images was denoted as the GTVpostCT. The MIM software system was used to deformably register the MRI and CT images.

Results

When based on the coincidence of the compared target centers, there were statistically significant increases in the conformity index (CI) and degree of inclusion (DI) values for GTVpostCT-GTVpreMR, GTVpostCT-CTVpreMR + 10, CTVpostCT + 10-GTVpreMR, and CTVpostCT + 10-CTVpreMR + 10 when compared with those based on the DIR of the thorax (Z = − 3.724, − 3.724, − 2.591, − 3.593, all P < 0.05; Z = -3.724, − 3.724, − 3.201, − 3.724, all P < 0.05, respectively).

Conclusions

Although based on DIR, there was relatively poor spatial overlap between the preoperative prone diagnostic MRI images and the postoperative prone CT simulation images for either the whole breast or the target volumes. Therefore, it is unreasonable to use preoperative prone diagnostic MRI images to guide postoperative target delineation for EB-PBI.

Keywords

  • Preoperative diagnostic magnetic resonance image
  • Postoperative prone computed tomography simulation image
  • Deformable image registration
  • Target volume comparison
  • External-beam partial breast irradiation

Background

Breast-conserving therapy (BCT), which involves a wide local excision followed by radiotherapy to the whole breast, has become the standard treatment for early-stage breast cancer [1]. However, for patients with a low risk of recurrence, accelerated partial breast irradiation (APBI) is now gaining acceptance as an alternative to whole breast irradiation (WBI) for early-stage cancer [26]. In addition, external-beam partial breast irradiation (EB-PBI) is an important approach to APBI. Polgar et al. [2] have reported that the efficacy of EB-PBI is equivalent to that of WBI. However, there are conflicting data regarding the acute and late toxicity of APBI. An Italian randomized trial has indicated [7] that the rates of Grades 1 and 2 acute skin toxicity in a APBI cohort were remarkably lower than those in a WBI group with decreases of 17 and 18.2%, respectively. However, in a prospective trial of 2135 patients from Canada [8], poor cosmesis at 3 years was significantly increased among those treated with APBI compared with WBI treatment, with 29% vs 17% as determined by trained nurses and 26% vs 18% as determined by the patients. Meanwhile, the rates of Grades 1 and 2 toxicity in the EB-PBI patients were also significantly higher than those in the WBI group.

Hence, based on these results, researchers are rethinking all aspects of postoperative EB-PBI. A potential factor that explains the increase in toxicity observed in the APBI group is the irradiation of a larger volume of breast tissue in those patients with poor cosmesis. Whether to ensure therapeutic efficacy or to reduce toxicity and side effects, an essential prerequisite for APBI is the accurate delineation of the target volume. However, defining the target in postoperative EB-PBI varies widely depending on the specimen volume, seroma size, clarity, surgical clips, simulation image, inter-observer variability [9] and other aspects. In addition, there is a volumetric difference for EB-PBI between the prone and supine positions [10]. Moreover, preoperative EB-PBI might be an effective approach to reducing the target volume compared to that in postoperative EB-PBI. It has been reported that both the gross tumor volume (GTV) and planning target volume (PTV) are significantly smaller in preoperative EB-PBI than in postoperative EB-PBI [11, 12].

Preoperative image-guided techniques have been considered effective tools for improving the detection of tumors [13], and due to its high spatial resolution, preoperative magnetic resonance imaging (MRI) has the advantages of detecting occult tumors and providing additional valuable information regarding the primary tumor [14, 15]. At present, there are few reports that focus on the feasibility of preoperative prone diagnostic MRI in guiding postoperative target delineation for prone EB-PBI. Therefore, the aim of this study was to provide a reference for how to use preoperative diagnostic MRI to guide the delineation of postoperative EB-PBI in the prone position.

Methods

Patient selection

Breast cancer patients who were suitable for EB-PBI after BCS were enrolled in this study. All the patients underwent preoperative diagnostic MRI in the prone position. Patients who had oncoplastic BCS were excluded from the trial, and equal or more than 5 surgical clips (2 mm in diameter) were used to mark the boundaries of the lumpectomy cavity. All of the enrolled patients had either no seroma or a seroma clarity score of 3 in the surgical cavity. None of the patients had chronic lung disease, and all exhibited normal arm movement after surgery. This research was performed in accordance with the relevant regulations, and all the patients in our research joined this study with informed consent and voluntarily underwent prone 3D CT simulation scanning. The study was approved by the institutional research ethics board of the Shandong Tumor Hospital Ethics Committee.

Image simulation and acquisition

Patients underwent preoperative prone diagnostic MRI that was performed with a Philips Achieva 3.0-T scanner (Amsterdam, Netherlands). The diagnostic MRI protocol began with preliminary imaging using fast-spin echo sagittal T2 with fat saturation, T2 weighted (T2w) turbo spin echo (TSE) with fat suppression [spectral adiabatic inversion recovery (SPAIR)]and axial T1 sequences. This was followed by dynamic high resolution simultaneous imaging of both breasts using the THRIVE sequence with 8 dynamic scans with fat saturation, performed after intravenous administration of a contrast agent (gadopentetate dimeglumine, 0.1 mmol/kg). Postprocessing consisted of 2 series of subtraction images. The total acquisition time of the preoperative diagnostic MRI protocols was 18 min. All the patients were placed in the prone position on the dedicated bilateral breast coil with no degree of incline. The coil contained two apertures open all sides to allow the bilateral breasts to hang freely away from the chest wall. The hands were naturally extended and placed on both sides of the head.

While undergoing postoperative CT simulation scanning with standard resolution, matrix 512 × 512, the patients were placed in the prone position on a dedicated treatment board (CIVCO Horizon™ Prone Breast Bracket- MTHPBB01) with no degree of incline using an arm support (with both arms above the head). The board contained an open aperture on one side to allow the ipsilateral breast to hang freely away from the chest wall. The MRI and CT images that were transferred to the MIM version 6.7.6 software (Cleveland, USA) were 3-mm thick.

Target volume delineation

All structures were delineated by the same radiation oncologist on both the preoperative diagnostic MRI and postoperative CT simulation images using the MIM system. MRI delineations were performed based on the preoperative T2WI images with voxel size 1 mm × 1.25 mm × 3 mm; the gross tumor was delineated based on hyperintense T2WI area (excluding the hypersignal gland around the primary tumor) and denoted as the GTVpreMR,. The clinical target volumes (CTVs) consisted of the GTVpreMR, plus 10-mm and 20-mm margins and were denoted as the CTVpreMR + 10 and CTVpreMR + 20, respectively. All of the CTVs were limited to 5 mm from the skin surface and the gland-pectoralis interface. The PTVs were expanded by 15-mm and 25-mm margins from the GTVpreMR, and were denoted as the PTVpreMR + 15 and PTVpreMR + 25, respectively. All of the PTVs were limited to 5 mm from the skin surface and lung-chest wall interface. While delineating the CTVBreast-MRI, the delineator considered referenced breast at time of MRI, including the apparent MRI glandular breast tissue and incorporating consensus definitions of anatomical range. After delineating, the MRI physician was asked to confirmed the target volumes defined using the preoperative diagnostic MRI (Fig. 1a).
Fig. 1
Fig. 1

The picture of target volumes based on preoperative prone diagnostic MRI or postoperative prone simulation CT (a preoperative diagnostic MRI; b postoperative simulation CT)

On the postoperative prone simulation CT images, the tumor bed was delineated based on the surgical clips alone and was defined as the GTVpostCT. The CTVpostCT + 10 was created by adding 10 mm to the GTVpostCT and was limited to 5 mm from the skin surface and the gland-pectoralis interface. The PTVpostCT + 15 was produced by equally extending the GTVpostCT by a 15-mm margin and was limited to 5 mm from the skin surface and the lung-chest wall interface. The ipsilateral breast was contoured over the obtained MRI and CT images. And the CTVBreast-CT was delineated by considering referenced breast at time of CT, including the apparent CT glandular breast tissue and incorporating consensus definitions of anatomical range (Fig. 1b).

Deformable image registration

This study applied the MIM system to perform the deformation registration. The VoxAlign Deformation Engine™ provided a registration algorithm for converting local registration into deformation registration in different modality images registrations. Meanwhile, the MIM system was a commercial software, so the algorithm details were not public. First, the main sequence and a subordinated sequence were selected for rigid registration. On this basis, the automatic deformation registration was implemented with set reference points, including the thorax and the center-coincidence of the compared targets. During the registration process of this study, the prone CT simulation was set to the main sequence, and the MRI T2WI image was used as the subordinated sequence. After the automatic deformation registration was completed, the Reg Reveal and Reg Refine tools were used to evaluate and revise the registration quality of the images to achieve the best visual effect (Fig. 2). The Reg Reveal tool was used for evaluating an image’s final deformable registration results in the primary area of concern and the Reg Refine tool would only be used in the event that, while evaluating the initial deformation with Reg Reveal, it was determined a poor alignment was identified that needs to fixed.
Fig. 2
Fig. 2

The picture of DIR based on the thorax and DIR based on the center-coincidence of the GTVpreMR - GTVpostCT (a based on the thorax; b based on the center-coincidence of the GTVpreMR -GTVpostCT)

Parameter evaluation

The target volumes defined using the preoperative diagnostic MRI and postoperative prone CT images were calculated separately. In addition, the correlations between the target volumes defined using the preoperative diagnostic MRI and the corresponding target volumes based on postoperative prone CT images were evaluated respectively.

The degree of inclusion (DI), the conformity index (CI) and Dice’s similarity coefficient (DSC) were calculated for the CTVBreast-MRI and CTVBreast-CT, the GTVpostCT and GTVpreMR, the GTVpostCT and CTVpreMR + 10, the CTVpostCT + 10 and GTVpreMR, and the CTVpostCT + 10 and CTVpreMR + 10. The DI was defined as follows:
$$ \mathrm{DI}\ \left(\mathrm{A},\mathrm{B}\right)=\frac{A\cap B}{A} $$
The definition of the DI of volume A included in volume B [DI (A in B)] was the percentage of the overlap between volume A and B in volume A [16]. The CI of volume A and B [CI (A, B)] was computed according to Struikmans et al. [17] The formula was as follows:
$$ \mathrm{CI}\ \left(\mathrm{A},\mathrm{B}\right)=\frac{A\cap B}{A\cup B} $$
which is defined as the ratio of the intersection of A with B to the union of A and B. DSC [18] is a commonly used metric in medical imaging and contouring studies and is defined as follows:
$$ \mathrm{DSC}=\frac{2\left(A\cap B\right)}{A+B}. $$
The three-dimensional coordinates of the targets were recorded for each patient. Next, the displacements between the targets in the left-right (LR), anterior-posterior (AP) and superior-inferior (SI) directions were obtained and were defined as Δx, Δy and Δz, respectively. The distance between of the centers of mass (COMs) of the targets was calculated using the following formula:
$$ \varDelta \mathrm{V}=\Big(\varDelta {\mathrm{x}}^2+\varDelta {\mathrm{y}}^2+\varDelta {z}^{2\Big)1/2} $$

Statistical analyses

Statistical analysis was performed using the SPSS 19.0 software (IBM Corporation, Armonk, NY, USA). The data that did not follow a normal distribution are described using medians and ranges. The Wilcoxon signed-rank test was used to compare the target volumes and relevant parameters. The Spearman rank correlation analysis was performed to establish the relevance of differences between the target volumes. The data were considered statistically significant at P < 0.05.

Results

Patient characteristics

The study population consisted of 30 patients with early-stage breast cancer who were suitable for EB-PBI after BCS from July 2016 to April 2017. Eighteen of the 30 patients who underwent preoperative diagnostic MRI enrolled in this study. The patients had a median age of 43 years (range, 39–69 years) and had cancer of the breast with a pathological stage of T1-T2N0M0. Seven of the 18 patients had left-sided breast cancer, and the remaining eleven had right-sided breast cancer. The patients underwent a lumpectomy, which was performed with a circumferential margin of at least 1.0 cm [19], with sentinel lymph node dissection (SLND) or axillary lymph node dissection (ALND), and tumor-negative margins were ensured during a single operation. The patient and tumor characteristics are presented in Table 1.
Table 1

Patient and tumor characteristics

Variables

Values

Age, years

 Median

43

 Range

39–69

Tumor size

 ≥ 10 mm < 20 mm

10

 ≥ 20 mm < 30 mm

8

Breast side

 Left

7

 Right

11

Localization of tumor bed

 UOQ

11

 LOQ

1

 Central portion of breast

0

 UIQ

2

 LIQ

4

Tumor characteristics

 Ductal carcinoma in situ

1

 Invasive ductal carcinoma

15

 Invasive lobular carcinoma

1

 Cribriform carcinoma

2

Abbreviations: UOQ upper outer quadrant, LOQ lower outer quadrant, UIQ upper inner quadrant, LIQ lower inner quadrant

Comparison of the target volumes and correlation analysis

The target volumes defined using preoperative prone MRI and postoperative prone CT are listed in Table 2. The median GTVpreMR, was 12.58 cm3 less than the median GTVpostCT (Z = -3.593, P = 0.000). After expanding the GTV with the described margins, the median values of the CTVpostCT + 10 and PTVpostCT + 15 were both significantly larger than those of the CTVpreMR + 10 and PTVpreMR + 15, respectively (Z = -3.593, − 2.983, both P < 0.05). Moreover, the median volume variability between the CTVpostCT + 10 and CTVpreMR + 20 and between the PTVpostCT + 15 and PTVpreMR + 25 was statistically significant (Z = -2.722, − 2.853, both P < 0.05). A statistically significant positive correlation was found between the GTVpreMR, and GTVpostCT, the CTVpreMR + 10 and GTVpostCT, and the CTVpreMR + 10 and CTVpostCT + 10 (r = 0.518, 0.474, 0.498; P = 0.028, 0.042, 0.047, respectively). However, there was no significant correlation between the PTVpreMR + 15 and PTVpostCT + 15 or the PTVpreMR + 25 and PTVpostCT + 15 (Table 3).
Table 2

Target volume defined using preoperative prone MRI and postoperative prone CT (cm3)

Target volume

Median

Range

GTVpreMR

4.64

1.34~19.06

CTVpreMR + 10

34.33

18.56~87.14

PTVpreMR + 15

71.05

41.48~150.57

CTVpreMR + 20

105.27

62.08~205.17

PTVpreMR + 25

162.00

92.27~260.95

GTVpostCT

17.22

9.04~42.46

CTVpostCT + 10

53.46

22.69~118.21

PTVpostCT + 15

118.01

79.29~227.08

Abbreviations: GTV gross tumor volume, CTV clinical target volume, PTV planning target volume, TB tumor bed

Table 3

Correlation between the target volumes defined using preoperative prone MRI and postoperative prone CT

Target volume

r-value

P-value

GTVpostCT- GTVpreMR

0.518

0.028

GTVpostCT- CTVpreMR + 10

0.483

0.042

GTVpostCT -CTVpreMR + 20

0.399

0.101

CTVpostCT + 10-CTVpreMR + 10

0.474

0.047

CTVpostCT + 10-CTV preMR + 20

0.498

0.053

PTVpostCT + 15- PTVpreMR + 15

0.401

0.099

PTV postCT + 15-PTV preMR + 25

0.377

0.123

Abbreviations: GTV gross tumor volume, CTV clinical target volume, PTV planning target volume, TB tumor bed

Comparison of the parameters of the target volumes defined using MRI and CT

When based on the DIR of the thorax, the median values of the CI, DI and DSC between the CTVBreast-MRI and CTVBreast-CT were 0.56, 0.82 and 0.71, respectively. The distance between the COM of the CTVBreast-MRI and CTVBreast-CT was 1.81 cm. When based on the DIR of the thorax, the median CIs for GTVpostCT-GTVpreMR, GTVpostCT- CTVpreMR + 10, CTVpostCT + 10-GTVpreMR, and CTVpostCT + 10-CTVpreMR + 10 were slightly lower than those based on the center-coincidence of the GTVpreMR and GTVpostCT; the median CI values for these volumes were 0.02, 0.07, 0.04 and 0.17; 0.19, 0.31, 0.05 and 0.38, respectively (Z = − 3.724, − 3.724, − 2.591, − 3.593, respectively; all P < 0.05). The DI and DSC median values for the GTVpostCT-GTVpreMR, the GTVpostCT-CTVpreMR + 10, the CTVpostCT + 10-GTVpreMR and the CTVpostCT + 10-CTVpreMR + 10 were generally low; however, there were statistically significant increases in these parameters based on the center-coincidence of the GTVpreMR and GTVpostCT when compared with those based on the DIR of the thorax (Z = − 3.724, − 3.724, − 3.201, − 3.724, all P < 0.05; Z = -3.724, − 3.724, − 2.591, − 3.636, all P < 0.05, respectively, Table 4).
Table 4

Parameter evaluation of the target volume defined using preoperative prone MRI and postoperative prone CT based on the DIR of the thorax or target center

Parameters

On DIR of the thorax

On DIR of the target center

Z-value

P-value

GTVpostCT -GTVpreMR

 CI

0.02 (0.00~0.18)

0.19 (0.06~0.48)

−3.724

0.000

 DI

0.08 (0.00~0.54)

0.85 (0.48~1.00)

−3.724

0.000

 DSC

0.03 (0.00~0.31)

0.32 (0.11~0.65)

−3.724

0.000

 ΔV

2.71 (0.55~7.21)

0.06 (0.02~1.91)

-3.724

0.000

GTVpostCT - CTVpreMR + 10

 CI

0.07 (0.00~0.23)

0.31 (0.17~0.48)

-3.724

0.000

 DI

0.27 (0.00~0.85)

0.86 (0.38~1.00)

-3.724

0.000

 DSC

0.13 (0.00~0.38)

0.47 (0.30~0.65)

-3.724

0.000

 ΔV

2.67 (1.00~6.42)

0.14 (0.04~1.96)

-3.724

0.000

CTVpostCT + 10- GTVpreMR

 CI

0.04 (0.00~0.16)

0.05 (0.01~0.20)

−2.591

0.010

 DI

0.66 (0.00~1.00)

1.00 (0.84~1.00)

−3.201

0.001

 DSC

0.07 (0.00~0.27)

0.09 (0.03~0.34)

−2.591

0.010

 ΔV

2.54 (0.55~6.57)

0.28 (0.04~1.70)

−3.724

0.000

CTVpostCT + 10- CTVpreMR + 10

 CI

0.17 (0.00~0.46)

0.38 (0.13~0.67)

−3.593

0.000

 DI

0.43 (0.00~0.90)

0.89 (0.65~0.99)

−3.724

0.000

 DSC

0.29 (0.00~0.63)

0.55 (0.24~0.80)

−3.636

0.000

 ΔV

2.67 (0.00~6.44)

0.21 (0.05~1.75)

−3.724

0.000

Abbreviations: CI the conformity index, DI the degree of inclusion, DSC Dice’s similarity coefficientm, ΔV: the distance between the COM of the targets

Discussion

APBI, as a possible alternative to WBI, offers less overall treatment time and the delivery of a reduced dose to uninvolved portions of the breast and adjacent organs at risk [20, 21]. Undoubtedly, the irradiation of normal breast tissue would be decreased by reducing the EB-PBI target volume, which provides conditions for reducing toxicity or other side effects and improving the cosmetic outcome [22]. During the EB-PBI target definition, first and foremost is the identification and contouring of the GTV. MRI is recognized as an excellent imaging tool in diagnosing a primary breast tumor and has shown the ability to identify mammographically occult carcinoma [14, 15]. In the preoperative APBI study of van der Leij et al. [11], a virtual plan was made for preoperative EB-PBI, which resulted in a reduction in the GTV compared to that with postoperative EB-PBI. Hence, we aimed to clarify whether the delineation of the target volumes for postoperative prone EB-PBI might benefit from preoperative prone diagnostic MRI and to provide a reference for how to use preoperative diagnostic MRI to guide the delineation of target volumes for postoperative EB-PBI in the prone position.

Based on our analysis, the results showed that the GTVpostCT was significantly larger than the GTVpreMR by 12.58 cm3. Van der Leij et al. [11] also confirmed that a statistically significant difference was evident between the preoperative GTV and the postoperative tumor bed (7.71 cc lower in the preoperative EB-PBI target volume). In addition, our study demonstrated that the CTVpreMR + 10 and PTVpreMR + 15 were significantly smaller than the CTVpostCT + 10 and PTVpostCT + 15, respectively. Compared to the CTVpostCT + 10 and PTVpostCT + 15, the CTVpreMR + 20 and PTVpreMR + 25 were significantly greater by 51.81 cm3 and 43.99 cm3, respectively. Hence, if the expanded margin was too large, the preoperative EB-PBI would lose the advantage of reducing the dose to the ipsilateral breast, and the main factor to consider for the margin extension is the subclinical range. Controversy exists regarding EB-PBI treatment in terms of the subclinical range. Faverly et al. [23] have shown that a 10-mm tumor-free margin gives the best positive predictive value for breast cancers of limited extent. At present, a lumpectomy is performed with an intended macroscopic margin of at least 1.0 cm [24], and this value also represented a subclinical range that had been covered by previous studies [25, 26]. Therefore, it is resonable to reconstruct the CTVMRI by adding a 1.0-cm margin around the GTVMRI. However, Schmitz et al. [13] indicated that typical treatment margins of 10 mm around the GTVMRI might include occult disease in 52% of patients for MRI-guided BCT. When expanded with a 20-mm margin around the GTVMRI, a subclinical lesion could also be found in one-fourth of the patients. This might have been a consideration for van der Leij et al. [27] in delineating the CTVMRI and PTVMRI by expanding around the GTVMRI with 20-mm and 25-mm margins, respectively. But, based on our result, the CTVpreMR + 20 and PTVpreMR + 25 were significantly greater, so the CTVMRI and PTVMRI by expanding around the GTVMRI with 20-mm and 25-mm margins should not be advised. In our study, in comparison with the CTVpostCT + 10 based on the postoperative TB, the CTVMRI was not expanded by 15 mm around the GTVpreMR; however, van der Leij et al.11 have shown that the difference was not statistically significant.

In theory, when there is equilateral excision around the primary tumor, there would be no significant difference between the CTVpreMR + 10 and CTVpostCT + 10, which are defined by expansion from the primary tumor based on preoperative MRI and by the postoperative TB, respectively. This seemingly contradictory difference can be explained by the asymmetric resection of the primary tumors [28]. If the anisotropic surgical margin caused by asymmetrical resection is taken into account, the volumes of the CTVpre and CTVpost are comparable [11]. Furthermore, Zhang AP et al. [28] and den Hartogh et al. [29] indicated that because the majority of surgeons subjectively perform BCS based on palpation of the boundaries, which results in the asymmetric resection of primary tumors, neither the resection specimen volume nor the TB correlate with the visible tumor volume based on preoperative MRI. However, in our study, the Spearman rank correlation demonstrated that a statistically significant positive correlation exists between the GTVpreMR and GTVpostCT and between the CTVpreMR + 10 and GTVpostCT. This finding might be explained by the fact that in addition to the determination of the resection range based on palpation, the preoperative imaging data, such as MRI scans, have recently played an increasingly significant role in BCS, and the anisotropy between the specimen edge and tumor edge has been reduced.

MRI is not only the basis for the implementation of preoperative EB-PBI but also helpful for selecting patients suitable for postoperative EB-PBI, guiding postoperative target delineation for EB-PBI [30, 31]. The preoperative diagnostic MRI image was obtained in the prone treatment position, which is the same position as that of prone EB-PBI after BCS. Theoretically, DIR between the preoperative diagnostic MRI and postoperative prone CT simulation images should be conducive to the determination of the targets for postoperative prone EB-PBI. However, our study concluded that when based on the DIR of the thorax, the CI, DI and DSC were all poor for both the GTVpreMR-GTVpostCT and CTVpreMR + 10-GTVpostCT comparisons. The distances between the COMs of the GTVpreMR-GTVpostCT and GTVpreMR + 10-GTVpostCT were 2.71 cm and 2.67 cm, respectively. Moreover, the breast spatial matching between preoperative diagnostic MRI and postoperative CT simulation was not ideal, showing that the CI, DI and DSC values for the CTVBreast-MRI-CTVBreast-CT did not reach 1, for perfect agreement between volumes.

The poor breast spatial matching might be mainly caused by the difference between the dedicated MRI bilateral breast coil and the dedicated treatment board for prone CT simulation. For preoperative diagnostic MRI, there are two apertures open on all sides to allow the bilateral breasts to hang freely away from the chest wall; however, the postoperative CT treatment board only contains an open aperture on one side, whereby only the ipsilateral breast can move away from the chest wall due to gravity in the prone position. Meanwhile, the contralateral breast is pulled away from the ipsilateral side by the baffle as much as possible, which might affect the natural overhang of the ipsilateral breast. Our results indicated that there was relatively poor spatial overlap between both the GTVpreMR and GTVpostCT and between the CTVpreMR + 10 and GTVpostCT. This result may be attributable to the poor breast spatial matching and could also be the result of the same spatial morphology among the GTVpreMR, CTVpreMR + 10 and GTVpostCT after DIR. Furthermore, from our analysis that was based on the DIR of the center-coincidence of the GTVpreMR and GTVpostCT, the CI, DI and DSC values for the GTVpreMR-GTVpostCT and the CTVpreMR + 10-GTVpostCT were significantly improved compared with those based on the DIR of the thorax; however, these values were still poor. Therefore, it is unreasonable to use preoperative prone diagnostic MRI images to guide the postoperative target delineation for EB-PBI.

Conclusions

Overall, in Chinese early-stage breast cancer patients enrolled to undergo prone EB-PBI, when defining the target based on the preoperative prone MRI images, the target volumes were significantly smaller when compared to those based on postoperative prone CT images. However, a statistically significant positive correlation was found between the MRI- and CT-based target volumes. Although based on DIR, there was relatively poor spatial overlap between the preoperative prone diagnostic MRI images and the postoperative prone CT simulation images for both the whole breast and the target volumes. Hence, it is unreasonable to use preoperative prone diagnostic MRI to guide postoperative target fusion delineation for EB-PBI. In fact, it is feasible to optimize the delineation of the postoperative EB-PBI target volumes by other means, such as clipping the surgical cavity by the surgical team in the presence of the radiation oncologist responsible for contouring for PBI and using respiratory gating with daily on board image verification before delivery of treatment can help in reducing the PTV margins. Further, studies on patterns of failure and adverse cosmetic outcome after EB-PBI can aid in refining the delineation techniques.

Abbreviations

ALND: 

Axillary lymph node dissection

AP: 

Anterior-posterior

APBI: 

Accelerated partial breast irradiation

BCS: 

Breast-conserving surgery

BCT: 

Breast-conserving therapy

CI: 

Conformity index

COMs: 

Centers of mass

CT: 

Computed tomography

CTV: 

Clinical target volume

DI: 

Degree of inclusion

DIR: 

Deformable image registration

DSC: 

Dice’s similarity coefficient

EB-PBI: 

External-beam partial breast irradiation

GTV: 

Gross tumor volume

LR: 

Left-right

MRI: 

Magnetic resonance imaging

PTV: 

Planning target volume

si: 

Superior-inferior

SLND: 

Sentinel lymph node dissection

TB: 

Tumor bed

WBI: 

Whole breast irradiation

Declarations

Acknowledgements

This manuscript was edited by American Journal Experts (AJE).

Funding

The National Key Research Program of China (No. 2016YFC0904700).

National Natural Science Foundation of China (No. 81703038).

Natural Science Foundation of Shandong Province (No. ZR2017PH006).

The Key Research Development Program of Shandong Province (No.2017GSF18102).

Availability of data and materials

The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.

Authors’ contributions

TY contributed to the study design, the patient enrollment, the data statistics and analysis and writing the manuscript. JBL and WW participated in the study design. MX and LX contributed to reviewing the delineation. QS, YJZ and XJL made important contributions in collecting the data and revising the content. All authors read and approved the final manuscript.

Ethics approval and consent to participate

Approval was obtained from the institutional research ethics board of the Shandong Tumor Hospital Ethics Committee.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

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Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

Authors’ Affiliations

(1)
School of Medicine and Life Sciences, University of Jinan-Shandong Academy of Medical Sciences, Jinan, Shandong province, China
(2)
Department of Radiation Oncology, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, 440 Jiyan Road, Jinan, 250117, China
(3)
Department of Medical Imaging, Shandong Cancer Hospital Affiliated to Shandong University, Shandong Academy of Medical Sciences, Jinan, Shandong province, China

References

  1. Clarke M, Collins R, Darby S, Davies C, Elphinstone P, Evans V, Godwin J, Gray R, Hicks C, James S, MacKinnon E, McGale P, McHugh T, Peto R, Taylor C, Wang Y, Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;366(9503):2087–106.View ArticleGoogle Scholar
  2. Polgár C, Fodor J, Major T, Sulyok Z, Kásler M. Breast-conserving therapy with partial or whole breast irraddiation: ten-year results of the Budapest randomized trial. Radiother Oncol. 2013;108(2):197–202. https://doi.org/10.1016/j.radonc.2013.05.008.View ArticlePubMedGoogle Scholar
  3. Polgár C, Ott OJ, Hildebrandt G, Kauer-Dorner D, Knauerhase H, Major T, Lyczek J, Guinot JL, Dunst J, Miguelez CG, Slampa P, Allgäuer M, Lössl K, Polat B, Kovács G, Fischedick AR, Fietkau R, Resch A, Kulik A, Arribas L, Niehoff P, Guedea F, Schlamann A, Pötter R, Gall C, Uter W, Strnad V, Groupe Européen de Curiethérapie of European Society for Radiotherapy and Oncology (GEC-ESTRO). Late side-effects and cosmetic results of accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation after breast-conserving surgery for low-risk invasive and in-situ carcinoma of the female breast: 5-year results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2017;18(2):259–68. https://doi.org/10.1016/S1470-2045(17)30011-6.View ArticlePubMedGoogle Scholar
  4. Polgár C, Van Limbergen E, Pötter R, Kovács G, Polo A, Lyczek J, Hildebrandt G, Niehoff P, Guinot JL, Guedea F, Johansson B, Ott OJ, Major T, Strnad V, GEC-ESTRO breast cancer working group. Patient selection for accelerated partial-breast irradiation (APBI) after breast-conserving surgery: Recommendations of the Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology (GEC-ESTRO) breast cancer working group based on clinical evidence (2009). Radiother Oncol. 2010;94:264–73. https://doi.org/10.1016/j.radonc.2010.01.014.View ArticlePubMedGoogle Scholar
  5. Smith BD, Arthur DW, Buchholz TA, Haffty BG, Hahn CA, Hardenbergh PH, Julian TB, Marks LB, Todor DA, Vicini FA, Whelan TJ, White J, Wo JY, Harris JR. Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology. J Am Coll Surg. 2009 Aug;209(2):269–77. https://doi.org/10.1016/j.jamcollsurg.2009.02.066.View ArticlePubMedGoogle Scholar
  6. Shah C, Vicini F, Shaitelman SF, Hepel J, Keisch M, Arthur D, Khan AJ, Kuske R, Patel R, Wazer DE. The American Brachytherapy Society consensus statement for accelerated partial breast irradiation. Brachytherapy. 2013;12:267–77. https://doi.org/10.1016/j.brachy.2017.09.004.View ArticlePubMedGoogle Scholar
  7. L L, Buonamici FB, Simontacchi G, Scotti V, Fambrini M, Compagnucci A, Paiar F, Scoccianti S, Pallotta S, Detti B, Agresti B, Talamonti C, Mangoni M, Bianchi S, Cataliotti L, Marrazzo L, Bucciolini M, Biti G. Accelerated partial breast irradiation with IMRT: New technical approach and interim analysis of acute toxicity in a phase III randomized clinical trial. Int J Radiat Oncol Biol Phys. 2010;77(2):509–15. https://doi.org/10.1016/j.ijrobp.2009.04.070.View ArticleGoogle Scholar
  8. Olivotto IA, Whelan TJ, Parpia S, Kim DH, Berrang T, Truong PT, Kong I, Cochrane B, Nichol A, Roy I, Germain I, Akra M, Reed M, Fyles A, Trotter T, Perera F, Beckham W, Levine MN, Julian JA. Interim cosmetic and toxicity results from RAPID : a randomized trial of accelerated partial breast irradiation using three-dimensional conformal external beam radiation therapy. J Clin Oncol. 2013;31(32):4038–45. https://doi.org/10.1200/JCO.2013.50.5511.View ArticlePubMedGoogle Scholar
  9. van Mourik AM, Elkhuizen PH, Minkema D, Duppen JC, Dutch Young Boost Study Group, van Vliet-Vroegindeweij C. Multiinstitutional study on target volume delineation variation in breast radiotherapy in the presence of guidelines /Variability among breast radiation oncologists in delineation of the postsurgical lumpectomy cavity. Radiother Oncol. 2010 Mar;94(3):286–91. https://doi.org/10.1016/j.radonc.2010.01.009.View ArticlePubMedGoogle Scholar
  10. Lakosi F, Gulyban A, Simoni SB, Nguyen PV, Cucchiaro S, Seidel L, Janvary L, Nicolas S, Vavassis P, Coucke P. The Influence of Treatment Position (Prone vs. Supine) on Clip Displacement, Seroma, Tumor Bed and Partial Breast Target Volumes: Comparative Study. Pathol Oncol Res. 2016;22:493–500. https://doi.org/10.1007/s12253-015-0028-3.View ArticlePubMedGoogle Scholar
  11. van der Leij F, Elkhuizen PH, Janssen TM, Poortmans P, van der Sangen M, Scholten AN, van Vliet-Vroegindeweij C, Boersma LJ. Target volume delineation in external beam partial breast irradiation: Less inter-observer variation with preoperative- compared to postoperative delineation. Radiother Oncol. 2014;110(3):467–70. https://doi.org/10.1016/j.radonc.2013.10.033.View ArticlePubMedGoogle Scholar
  12. Nichols EM, Dhople AA, Mohiuddin MM, Flannery TW, Yu CX, Regine WF. Comparative analysis of the post-lumpectomy target volume versus the use of pre-lumpectomy tumor volume for early-stage breast cancer: implications for the future. Int J Radiat Oncol Biol Phys. 2010;77(1):197–202. https://doi.org/10.1016/j.ijrobp.2009.04.063.View ArticlePubMedGoogle Scholar
  13. Schmitz AC, van den Bosch MA, Loo CE, Mali WP, Bartelink H, Gertenbach M, Holland R, Peterse JL, Rutgers EJ, Gilhuijs KG. Precise correlation between MRI and histopathology – Exploring treatment margins for MRI-guided localized breast cancer therapy. Radiother Oncol. 2010;97(2):225–32. https://doi.org/10.1016/j.radonc.2010.07.025.View ArticlePubMedGoogle Scholar
  14. Onesti JK, Mangus BE, Helmer SD, Osland JS. Breast cancer tumor size: correlation between magnetic resonance imaging and pathology measurements. Am J Surg. 2008;196(6):844–8; discussion 849-50. https://doi.org/10.1016/j.amjsurg.2008.07.028.View ArticlePubMedGoogle Scholar
  15. van der Velden AP S, Boetes C, Bult P, Wobbes T. Magnetic resonance imaging in size assessment of invasive breast carcinoma with an extensive intraductal component. BMC Med Imaging. 2009;7:9–5. https://doi.org/10.1186/1471-2342-9-5.View ArticleGoogle Scholar
  16. H H, Rhein B, Haering P, Kopp-Schneider A, Debus J, Herfarth K. 4D-CTbased target volume definition in stereotactic radiotherapy of lung tumours: comparison with a conventional technique using individual margins. Radiother Oncol. 2009;93(3):419–23. https://doi.org/10.1016/j.radonc.2009.08.040.View ArticleGoogle Scholar
  17. H S, Wárlám-Rodenhuis C, Stam T, Stapper G, Tersteeg RJ, Bol GH, Raaijmakers CP. Interobserver variability of clinical target volume delineation of glandular breast tissue and of boost volume in tangential breast irradiation. Radiother Oncol. 2005;76(3):293–9.View ArticleGoogle Scholar
  18. R C, Castillo E, Martinez J, Guerrero T. Ventilation from fourdimensional computed tomography: density versus Jacobian methods. Phys Med Biol. 2010;55(16):4661–85. https://doi.org/10.1088/0031-9155/55/16/004.View ArticleGoogle Scholar
  19. Rutgers EJ, EUSOMA Consensus Group. Quality control in the locoregional treatment of breast cancer. European Journal of Cancer. 2001;37(4):447–53.View ArticleGoogle Scholar
  20. BD S, Arthur DW, Buchholz TA, Haffty BG, Hahn CA, Hardenbergh PH, Julian TB, Marks LB, Todor DA, Vicini FA, Whelan TJ, White J, Wo JY, Harris JR. Accelerated partial breast irradiation consensus statement from the American Society for Radiation Oncology (ASTRO). J Am Coll Surg. 2009;209(2):269–77. https://doi.org/10.1016/j.jamcollsurg.2009.02.066.View ArticleGoogle Scholar
  21. Mózsa E, Mészáros N, Major T, Fröhlich G, Stelczer G, Sulyok Z, Fodor J, Polgár C. Accelerated partial breast irradiation with external beam three-dimensional conformal radiotherapy : five-year results of a prospective phase II clinical study. Strahlenther Onkol. 2014;190(5):444–50. https://doi.org/10.1007/s00066-014-0633-1.View ArticlePubMedGoogle Scholar
  22. Palta M, Yoo S, Adamson JD, Prosnitz LR, Horton JK. Preoperative single fraction partial breast radiotherapy for early-stage breast cancer. Int J Radiat Oncol Biol Phys. 2012;82(1):37–42. https://doi.org/10.1016/j.ijrobp.2010.09.041.View ArticlePubMedGoogle Scholar
  23. DR F, Hendriks JH, Holland R. Breast carcinomas of limited extent: frequency, radiologic-pathologic characteristics, and surgical margin requirements. Cancer. 2001;91(4):647–59.View ArticleGoogle Scholar
  24. Rutgers EJ. Quality control in the locoregional treatment of breast cancer. Eur J Cancer. 2001;37:447–53.View ArticleGoogle Scholar
  25. RM C, Wilkinson RH, Miceli PN, MacDonald WD. Breast cancer: Experiences with conservation therapy. Am J Clin Oncol (CCT). 1987;10:461–8.View ArticleGoogle Scholar
  26. Faverly DR, Burgers L, Bult P, Holland R. Three dimensional imaging of mammary ductal carcinoma in situ: Clinical implications. Semin Diagn Pathol. 1994;11(3):193–8.PubMedGoogle Scholar
  27. van der Leij F, Bosma SC, van de Vijver MJ, Wesseling J, Vreeswijk S, Rivera S, Bourgier C, Garbay JR, Foukakis T, Lekberg T, van den Bongard DH, van Vliet-Vroegindeweij C, Bartelink H, Rutgers EJ, Elkhuizen PH. First results of the preoperative accelerated partial breast irradiation (PAPBI) trial. Radiother Oncol. 2015;114(3):322–7. https://doi.org/10.1016/j.radonc.2015.02.002.View ArticlePubMedGoogle Scholar
  28. A Z, Li J, Wang W, Wang Y, Mu D, Chen Z, Shao Q, Li F. A comparison study between gross tumor volumes defined by preoperative magnetic resonance imaging, postoperative specimens, and tumor bed for radiotherapy after breast-conserving surgery. Medicine (Baltimore). 2017;96(2):e5839. https://doi.org/10.1097/MD.0000000000005839.View ArticleGoogle Scholar
  29. den Hartogh MD, van Asselen B, Monninkhof EM, van den Bosch MA, van Vulpen M, van Diest PJ, Gilhuijs KG, Witkamp AJ, van de Bunt L, Mali WP, van den Bongard HJ. Excised and irradiated volumes in relation to the tumor size in breast-conserving therapy. Breast Cancer Res Treat. 2011;129(3):857–65. https://doi.org/10.1007/s10549-011-1696-7.View ArticleGoogle Scholar
  30. Pengel KE, Loo CE, Teertstra HJ, Muller SH, Wesseling J, Peterse JL, Bartelink H, Rutgers EJ, Gilhuijs KG. The impact of preoperative MRI on breast-conserving surgery of invasive cancer: a comparative cohort study. Breast Cancer Res Treat. 2009;116(1):161–9. https://doi.org/10.1007/s10549-008-0182-3.View ArticlePubMedGoogle Scholar
  31. Tendulkar RD, Chellman-Jeffers M, Rybicki LA, Rim A, Kotwal A, Macklis R, Obi BB. Preoperative breast magnetic resonance imaging in early breast cancer: implications for partial breast irradiation. Cancer. 2009 Apr 15;115(8):1621–30. https://doi.org/10.1002/cncr.24172.View ArticlePubMedGoogle Scholar

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© The Author(s). 2019

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