Geometric factor analysis for dose distribution in the whole breast irradiation

doi:10.21203/rs.3.rs-4044413/v1

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Geometric factor analysis for dose distribution in the whole breast irradiation

https://doi.org/10.21203/rs.3.rs-4044413/v1

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Background

Protecting the heart and left lung is important for left-sided breast cancer radiotherapy. So，this study was to investigate the effect of geometric parameters on the dose of left lung and heart in whole breast radiotherapy.

Methods

A plan was designed for each patient using VMAT technology for thirty patients. A triangular ABC of the target was defined layer by layer. The geometric parameters were defined: Rat-H (the ratio of heart), Rat-L (the ratio of lung), the curvature and thickness of the target ρ and d. Explored the relationships between these parameters and the dose-volume of heart (V_5,h, V_10,h, V_20,h, MHD) and left lung (V_5,LL, V_10,LL, V_20,LL, V_30,LL, V_40,LL, MLD).

Results The V_5,h, V_10,hand MHD were all significantly associated with Rat-H (p<0.05). The V_5,LL, V_10,LL, V_20,LL, V_30,LL, V_40,LL and MLD were all significantly associated with Rat-L (p<0.05). And the V_20,LL, V_30,LL and V_40,LL were all significantly associated with d (p<0.05). Meanwhile，V_30,LL and V_40,LL were all significantly associated with ρ (p<0.05) . The correlations of the dose-volume of left lung and the four geometric parameters could be expressed by linear functions.

Conclusions

The geometric parameters Rat-H, Rat-L, d and ρ were closely related to the dose-volume of heart and left lung in whole breast radiotherapy.

geometric parameters

dose-volume

correlations

whole breast radiotherapy

left lung

heart

The application of B-ultrasound, mammography, PET and other diagnosis methods has increased the detection rate of early breast cancer. Breast-conserving surgery combined with radiotherapy has become a more preferred choice for patients with high quality of life and aesthetic effects [1–3]. Adjuvant whole breast radiotherapy (WBRT) with conventional fractionation or hypofractionation is presently considered the standard of care after breast-conserving surgery (BCS) for in situ and invasive breast cancer at an early stage [4–8]. In addition, some studies showed that a boost dose to the tumor bed might furtherly raise local control in a subset of patients [9, 10]. In addition, in order to reduce the radiation induced toxicity, partial breast radiotherapy (PBRT) is also an optional method for postoperative radiotherapy for early breast cancer, but the efficacy of PBRT has been controversial. From two recent retrospective reviews, the local control rates from PBRT were slightly lower than WBRT [11, 12]. Therefore, in many radiation oncology centers, WBRT is still selected as the postoperative treatment for early breast cancer.

WBRT plans are technically challenging because of the target being long and narrow and adjacent to the body surface. Tangential wedge field technique was origially selected. However, this technique results in significant dose heterogeneity [13]. In order to balance the curative effect of radiotherapy and long-term complications, sparing organs at risk (OAR) such as ipsilateral lung (IL), contralateral lung (CL), heart and contralateral breast (CB), we constantly improve the technique. The most common RT techniques available for whole breast irradiation in a linear accelerator setup are bi-tangential 3-dimensional conformal radiotherapy (3DCRT), field-in-field (FIF), intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) [13–18]. The conventional FIF technique provides inhomogeneous target dose, hot spots outside the target and high dose irradiation to OAR. In contrast, IMRT and VMAT techniques provide better dose conformity, homogeneity and can spare more OAR from high dose.

No matter which technology is selected for WBRT, the geometric relationship between OARs and the targets is an important impact on dose distribution. Although the current gold standard for calculating cardiac dose is the computed tomography (CT) treatment planning with manual contouring of cardiac structures, Taylor et al demonstrated that maximum heart distance (MHD', for distinguishing abbreviation of mean heart dose in the following, the MHD' referred to mean heart distance) provided a reliable parameter for estimating dose to cardiac tissue. The impact of radiation treatment on heart and lung dose-volume is largely dependent on the maximal heart distance (MHD') & central lung distance (CLD) [19–23]. MHD' and CLD have a role in predicting the heart and lung volume at different dose levels. Measured MHD' & CLD are considered as important tools for estimating cardiac dose in patients treated with tangential fields. There is also a correlation between MHD' and NTCP of cardiac mortality. Central lung distance (CLD) is considered as a significant indicator of ipsilateral irradiated lung. Reduction of CLD limits the dose to the lung and can significantly limit pulmonary toxicity.

However, in the actual work, we found that the doses of ipsilateral lung and heart were not only related to MHD' and CLD, but also related to some other geometric parameters. In this study, we selected several original geometric parameters, such as high-base ratio, etc., and discussed the relationship between these parameters and the dose of OARs.

1.1 Immobilization and CT scan

30 patients with early left breast cancer after breast-conserving surgery in our hospital were selected. Patients were imaged on a conventional supine breast board (R610-DCF, Klarity Medical & Equipment Co. Ltd. Guangzhou, China) with arms above the head to adequately expose the breast and lower limbs being naturally bent. Free-breathing CT scans were performed using a large-aperture CT system (SOMATOM Sensation Open 24, Siemens, Germany) without contrast, starting from the lower edge of C2 to the upper edge of L3 with a slice thickness of 3.0 mm. The CT scan images were transferred to the Treatment Planning System.

1.2 Target delineation and planning design

CTV and organs at risk (OARs) were contoured manually according to the Radiation Therapy Oncology Group (RTOG) breast cancer atlas [24]. The CTV was contoured by experienced doctors. The range of CTV was up to the clavicular heads(cranially), down to the farthest visible breast contour(caudally), to the perforating mammary vessels or to the edge of the sternum (medially), to the anterior edge of the latissimus dorsi (laterally), to the junction of the breast tissue and the pectoralis muscles (posteriorly), and up to 5 mm under the skin surface (anteriorly). The upper boundary of CTV is located at the lower edge of the clavicle head, the inner boundary does not exceed the lateral border of the sternum, the outer boundary is located at the anterior edge of the latissimus dorsi muscle, the lower boundary is located at the 5 mm below the breast fold, approximately at the level where the apex disappears, the anterior boundary is 5 mm below the skin border, and the posterior boundary does not exceed the superficial fascia of the pectoralis muscle. The CTV was delineated based on the glandular breast tissue visible on the CT images. Planning target volume (PTV) were generated by the addition of three-dimensional, 5 mm margins to the CTV up to 5 mm from the skin. OARs included left lung, right lung, heart, right breast, and spinal cord. Volumetric-modulated arc therapy (VMAT) plans were designed by the same medical physicist under the same optimization conditions. The doses to targets and OARs all met the clinical requirements.

1.3 Definition of geometric parameters

Geometric parameters in an example are shown in Fig. 1. A triangle ABC was obtained from the intersection of the tangent fields of each level of PTV and the internal, external and anterior margins of PTV, the length of the bottom side of the triangle (l) was the line between the two points A, B which was parallel to the inner tangent field and intersecting the internal and external limit of the PTV. The line at points Q, N was h₁ which was the maximum distance from the bottom edge to posterior margin of the PTV. With the bottom as a perpendicular line, the distance to the vertex of the triangle is the height of the triangle h₂ which was the line of P, C points. The ratio of h₂ to l (h₂/l) was defined as the curvature r of the PTV, namely r = h₂/l, and the arithmetic average of r in all CT layers was denoted by ρ. And t defined as the thickness of the PTV which was h2 minus h1, namely t = h2-h1, and the arithmetic average of t in all CT layers was denoted by d. The overlapping volume of the triangle ABC with the left lung and heart were defined as V_L and V_H, respectively. The ratio of the V_L and V_H to the left lung and heart volume were Rat-L (the ratio of lung) and Rat-H (the ratio of heart), respectively. The target triangle ABC was delineated layer by layer and the relevant parameter data were measured and collected.

1.4 Statistical analysis

The experimental data were analyzed by SPSS 25 statistical software. Pearson and Spearman correlation analysis were used to explore the correlation between geometrical parameters and dosimetric metrics. Differences were considered significant at p values < 0.05.

In the Table 1, it could easily be seen that the V_5,h, V_10,h and MHD were all significantly associated with Rat-H (p < 0.05). (Note: Here, the V_5,h, V_10,h referred to the heart V₅, V₁₀, the footmark "h" referred to the heart, MHD referred to the mean heart dose; For distinguishing them from the V₅, V₁₀ of the left lung, the foot of the left lung was labeled "LL", MLD referred to the mean left-lung dose.) In the Table 2, it had been observed that The V_5,LL, V_10,LL, V_20,LL, V_30,LL, V_40,LL and MLD were all significantly associated with Rat-L (p < 0.05). And the V_20,LL, V_30,LL and V_40,LL were all significantly associated with d (p < 0.05). Meanwhile, V_30,LL and V_40,LL were all significantly associated with ρ (p < 0.05). In addition, the relationships between the dosimetric metrics V_{x, LL}, MLD and the geometric parameters ρ, d, Rat-L could be described as simple linear regression formulations by least-square fitting method. (Note: the footmark "x" referred to various accumulative doses at 10, 20, 30, 40Gy) the results indicated that there is a noticeable correlativity between V_{x, LL}, MLD and ρ, d or Rat-L, and the percentage volume (%) of left lung approximated 45、38、27 and 14 times to the Rat-L for V_10,LL, V_20,LL, V_30,LL and V_40,LL respectively.

Table 1

Relationships between various dose-volume of heart and geometric parameters.
geometric parameters	dose-volume of heart	R(Rho)	P
ρ	V_5,h	-0.04	0.835
	V_10,h	-0.165	0.385
	V_20,h	-0.191	0.312
	MHD	-0.029	0.88
d	V_5,h	-0.059	0.756
	V_10,h	-0.165	0.384
	V_20,h	-0.145	0.445
	MHD	-0.017	0.929
Rat-L	V_5,h	-0.213	0.258
	V_10,h	-0.332	0.073
	V_20,h	-0.368	0.045
	MHD	-0.241	0.199
Rat-H	V_5,h	0.431	0.017
	V_10,h	0.399	0.029
	V_20,h	0.305	0.101
	MHD	0.428	0.018
Note: Here, the V_5,h, V_10,h referred to the heart V₅, V₁₀, the footmark "h" referred to the heart. Rat-L: the ratio of overlapping left lung and triangle volume to the whole lung volume, Rat-H: the ratio of overlapping heart and triangle volume to the whole heart volume.

Table 2

Relationships between various dose-volume of left lung and geometric parameters.
geometric parameters	dose-volume of left lung	R(Rho)	P
ρ	V_5,LL	0.064	0.739
	V_10,LL	-0.201	0.287
	V_20,LL	-0.307	0.099
	V_30,LL	-0.370	0.044
	V_40,LL	-0.459	0.011
	MLD	-0.167	0.377
d	V_5,LL	0.017	0.93
	V_10,LL	-0.291	0.118
	V_20,LL	-0.388	0.034
	V_30,LL	-0.438	0.015
	V_40,LL	-0.503	0.005
	MLD	-0.231	0.22
Rat-L	V_5,LL	0.540	0.002
	V_10,LL	0.468	0.009
	V_20,LL	0.566	0.001
	V_30,LL	0.506	0.004
	V_40,LL	0.435	0.016
	MLD	0.545	0.002
Rat-H	V_5,LL	-0.068	0.72
	V_10,LL	-0.12	0.527
	V_20,LL	-0.169	0.372
	V_30,LL	-0.179	0.344
	V_40,LL	-0.229	0.224
	MLD	-0.122	0.52
Note: Here, the V_5,LL, V_10,LL referred to the left lung V₅, V₁₀, the footmark "LL" referred to left lung.

In this work, the four geometric parameters were extracted in order to examine the relationship between the geometric parameters and cardiac or pulmonary various dose-volume. The four geometric parameters are d, ρ, Rat-L and Rat-H respectively.

Table 1 showed the relationships between the four geometric parameters and various dose-volume of heart. It was observed that the Rat-H was positive correlation with the dose-volume of heart. Remarkably, the V_5,h, V_10,h and MHD had obvious statistical significance with Rat-H (p < 0.05), which should be due to the larger the heart volume overlapped with triangle ABC, the more dose the heart received form X-ray generated by accelerator. Furthermore, it also could be observed that Rat-L had obvious statistical significance with the percentage volume of heart at 20Gy (p < 0.05) from the Table1. But the Rat-L was negative correlation with the V_20,h (R=-0.368). This result should be related to the planning design that the percentage volume of left lung at 20Gy (V_{20, LL}) was more concerned.

Hence, the 20Gy dose deposition had less pathway into the left lung resulting in higher heart dose contributed to the V_20,h. Besides, there were no significant statistic difference from the Rat-L, ρ and d metrics related to cardiac dosimetry parameters showed in Table 1.

In addition, Table 2 showed the relationships between the various left lung dose-volume metrics and the four geometric parameters. It was observed that the Rat-L was strongly positive correlation with the dose-volume of the left lung, and the Rat-L had significant statistical significance with the dose-volume of the left lung at various accumulative doses, including V_5,LL, V_10,LL, V_20,LL, V_30,LL, V_40,LL, and MLD. It could be due to the larger left lung volume overlapped with the triangle ABC, the more dose the left lung received, and the Rat-L had a greater impact on the left lung compared with the Rat-H to the heart. Notably, it could be found from Fig. 1 or Fig. 2 that the overlapping volume of left lung and triangle ABC was much larger than that of heart. Meanwhile, we noted that the curvature ρ and thickness d of target had significant influence on left lung dose compared to heart, the curvature ρ and thickness d had great negative correlations with V_30,LL and V_40,LL. It was also easily illustrated by the Fig. 2 sketch that showed the thinner chest (gold arrow) overlapped the more volume of lung or heart with the triangle. So the thickness d of breast area exhibited strongly negative correlation with V_20,LL, V_30,LL, and V_40,LL.

Based on the Table 2, it could easily be seen that the different left lung dose-volume metrics were correlated with ρ、d、Rat-L. There was a trend of positive correlation observed between different left lung dose-volume metrics and geometric parameters which is Rat-L(R = 0.435 ~ 0.566), whereas there were also some geometric parameters such as ρ、d have negative correlations among these dosimetric parameters (R=-0.503~-0.37). The correlation of geometric parameters of PTV and left lung dose-volume metrics can be expressed as the following simple empiric relation by linear regressions:

V_10,LL=14.99 + 45.237×Rat-L(R = 0.468), V_20,LL=6.369 + 38.049×Rat-L(R = 0.566), V_30,LL=3.171 + 27.031×Rat-L(R = 0.506), V_40,LL=1.277 + 13.911×Rat-L(R = 0.435), MLD = 5.89 + 15.73×Rat-L(R = 0.545); V_20,LL=15.077–1.417×d(R=-0.388), V_30,LL=9.931–1.203×d(R=-0.438), V_40,LL=5.503–0.876×d(R=-0.503); V_30,LL=13.5-18.905 × ρ(R=-0.370), V_40,LL=8.525–14.89 × ρ(R=-0.459).

Based on the above the formulations, for example, MLD could be approximately estimated as 15 times the Rat-L, whereas the percentage volume (%) of left lung approximated 45、38、27 and 14 times to the Rat-L for V_10,LL, V_20,LL, V_30,LL and V_40,LL respectively. As the examples of the formulation, Fig. 3 showed the V_{x, LL} as a function of Rat-L, Fig. 4 showed the MLD as a function of Rat-L. Figure 5 showed the V_{x, LL} as a function of d, Fig. 6 shows the V_{x, LL} as a function of ρ, respectively.

From the four figures, it was obviously that there was a trend of positive correlation between Rat-L and these different lung dose-volume metrics while d and ρ had negative correlations with these metrics. The impact of geometric parameters on the left lung dose-volume was largely dependent on the Rat-L, likewise, ρ, d influenced the left lung dose-volume. When the PTV was thicker, the degree of bending was greater, it significantly decreased the volume of lung receiving high dose ( ≧ 30 and ≧ 40 Gy), except that the Rat-L was more remarkable for these patients with reducing lung volume receiving different dose levels. These results potentially suggested that the Rat-L, Rat-H, ρ or d metrics really had certain reference significance for pulmonary or cardiac dose prediction [25–29] of postoperative left breast preservation patients.

Overall, our study has demonstrated that the four geometric parameters were related to the dose-volume of lung or heart, and it was a pioneering investigation for the Rat-L, Rat-H, ρ or d metrics applied in the postoperative left breast preservation patients. Furthermore, these parameters could be potentially extended to be a novel approach to implement the investigation of the dosimetry prediction in artificial intelligence for postoperative breast-conserving patients.

WBRT: whole breast radiotherapy

BCS: breast-conserving surgery

PBRT: partial breast radiotherapy

OAR: organs at risk

IL: ipsilateral lung

CL: contralateral lung

CB: contralateral breast

3DCRT: 3-dimensional conformal radiotherapy

FIF: field-in-field

IMRT: intensity modulated radiotherapy

VMAT: volumetric modulated arc therapy

CLD: Central lung distance

RTOG: Radiation Therapy Oncology Group

PTV: Planning target volume

Rat-L: the ratio of lung

Rat-H: the ratio of heart

Acknowledgements

Not applicable.

Authors’ contributions

F.H.C., X.P. and X.H.L. contributed equally to this work. F.H.C. and X.P. co-drafted the manuscript, R.W. collected and analyzed the data. X.P., R.W. and Q.Y.L. drew the ﬁgures and tables. H.B. designed the study and revised the work. R.W., Q.Y.L., S.M.T. and Y.W.K. helped the data acquisition and collection. H.B. and F.H.C. made the final approval of the version to be published. All authors read and approved the final manuscript.

Funding

This work was financially supported by Project of Science, Technology Department of Yunnan Province and Kunming Medical University (202101AY070001-164).

Availability of data and materials

All the data generated or analyzed during this study are included in this published article. The datasets used and/or analyzed during the current study are available from the corresponding author.

Ethics approval and consent to participate

This study was approved by the ethics committee of Tumor Hospital of Yunnan Province (approval no. KYLX2022123). We certify that the study was performed in accordance with the Declaration of Helsinki and later amendments. Every human participant volunteered for the study and written informed consent was obtained from individual or guardian participants.

Consent for publication

Agreed.

Competing interests

The authors declare no competing interests.

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No competing interests reported.

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Geometric factor analysis for dose distribution in the whole breast irradiation

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Abstract

Figures

1 Introduction

2 Materials and Methods

1.1 Immobilization and CT scan

1.2 Target delineation and planning design

1.3 Definition of geometric parameters

1.4 Statistical analysis

3 Results

4 Discussions

5 Conclusion

Abbreviations

Declarations

References

Additional Declarations

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