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 Table of Contents  
Year : 2020  |  Volume : 16  |  Issue : 6  |  Page : 1336-1343

Method to prevent the target volume from escaping out of the field in breast irradiation: Forming a “fall-off margin”

Department of Radiation Oncology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkey

Date of Submission02-Oct-2019
Date of Decision10-Apr-2020
Date of Acceptance06-May-2020
Date of Web Publication09-Oct-2020

Correspondence Address:
Sema Yilmaz Rakici
Department of Radiation Oncology, Faculty of Medicine, Recep Tayyip Erdogan University, .slampasa Mah, Sehitlik Sok, 53100 Rize
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jcrt.JCRT_823_19

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 > Abstract 

Objectives: We aimed to obtain data that would enable the selection of the appropriate radiotherapy technique for whole breast irradiation (WBI) based on patients' physical characteristics and to evaluate the benefit of the new fall-off (FO) margin technique.
Materials and Methods: Ten patients with left-sided breast-conserving surgery, treated for breast carcinoma between August 2016 and September 2017, were included. The FO margin was created in five different plans of which two were formed by expanding the target volume out of the skin. The dose evaluation planning was statistically compared by calculating the target volume dosimetric parameters and the doses received by the organs at risk (OARs) for each technique. The volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy plans were considered ideal for WBI homogeneity and conformity indices, while the three-dimensional conformal radiotherapy (3DCRT) plan was considered nonideal.
Results: The increase in the breast x-axis length values and equivalent spherical diameter (ESD) dimension decreased the ideal value, whereas the increase in y-axis length values and ESD dimension correlated significantly with the D98 increase. The techniques were significantly correlated with OARs, such as V5, heart max, left anterior descending artery maximum, ipsilateral lung V5 and V20, and contralateral breast V5. Monitor unit values were significantly low in the 3DCRT and VMAT plans.
Conclusion: The new FO margin structure will have benefits for practical application because the head designs of linear accelerators and collimators and the target-Jaw/MLC distance are adjacent to the breast tissue, which moves during treatment.

Keywords: Breast cancer, breast-conserving surgery, fall-off margin, intensity-modulated radiotherapy, radiotherapy, volumetric-modulated arc therapy

How to cite this article:
Rakici SY, Eren M. Method to prevent the target volume from escaping out of the field in breast irradiation: Forming a “fall-off margin”. J Can Res Ther 2020;16:1336-43

How to cite this URL:
Rakici SY, Eren M. Method to prevent the target volume from escaping out of the field in breast irradiation: Forming a “fall-off margin”. J Can Res Ther [serial online] 2020 [cited 2021 Nov 27];16:1336-43. Available from: https://www.cancerjournal.net/text.asp?2020/16/6/1336/297627

 > Introduction Top

Whole breast irradiation (WBI) is the main treatment modality for managing patients undergoing breast-conserving surgery (BCS). Three-dimensional conformal radiotherapy (3DCRT) is still an indispensable treatment option for WBI.[1],[2],[3] Early data on intensity-modulated radiotherapy (IMRT) use suggest that it produces more uniform dose distribution in target volumes while reducing the organs at risk (OARs) dose than conventional RT techniques.[4]

IMRT applications are implemented by various methods such as volumetric modulated arc therapy (VMAT), which allows radiation doses to be delivered by rotation, sliding window/dynamic IMRT, and step-and-shoot/static IMRT.[5],[6],[7] A WBI technique that does not increase clinical workforce and treatment time is 3DCRT. According to analyses, dose distribution quality targets and OARs doses have improved through better planning and dosing methods such as IMRT and VMAT.[8],[9] However, these have disadvantages: (1) the planning time depends on the operator and is based on the planner's experience, and (2) long treatment duration, and in most countries, IMRT represents a more expensive treatment. These disadvantages, despite proven clinical advantages, have led to IMRT's slow acceptance in breast cancer treatments.[10]

To our knowledge, this is the first study to develop a method to prevent the target volume's movement out of the irradiation site during breast irradiation.

Here, the factors impacting the choice of treatment technique for WBI patients were investigated using dosimetric calculations to evaluate the benefits of fall-off (FO) margins.

 > Materials and Methods Top

This is a single-institute retrospective study done on carcinoma breast patients diagnosed and treated at our institute from August 2016 to September 2017.

Patient selection

Ten patients with left-sided BCS, treated for breast carcinoma, were included. In a retrospective archive scan, numerous samples with a 3-mm section thickness, scanned from the upper level of the larynx and including both lungs, were selected from the Aquilion LB scanner (Toshiba Medical Systems, Tokyo, Japan) brand computed tomography (CT) device. The samples were from CTs of patients who were placed prone on the breast board (MAX3™ PLUS Breast Board, USA), while the area was elevated parallel to the upper part of both arms and the sternum.

Contouring of target and normal structures

Contouring of clinical target volume (CTV), planned target volume (PTV), and OARs volumes for patients' normal tissue and planning targets was appropriately redrawn over all patients' CT data sets.[11] The 3-mm retraction of the PTV breast surface from the skin surface was performed to avoid uncertainties in planning systems when calculating the skin dose.[12] A new contour called “fall-off margin” that extends the PTV beyond the skin was formed because of the PTV breast sagging or swelling from edema during RT and due to breast movements caused by respiratory movement. [Figure 1]a shows a contour with a FO margin.
Figure 1: Fall-off margin and x and y dimensions. (a) Creating a fall-off margin contour. (b) X and y distance measurement for two-dimensional breast size

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This new contour was created as a 10-mm gap volume area from the skin to the outer perimeter of the PTV. Thus, a 7-mm-wide zone with air was built up from under the skin for PTV. This region was used during IMRT and VMAT planning optimization. The FO plans were called IMRT-FO and VMAT-FO. Additionally, two- and three-dimensional lengths of the irradiated breast volume, defined as CTV, were calculated. The tangential area horizontal dimension in the widest x plane was taken as the x dimension, and the vertical distance between the nipple and chest wall was used as the y dimension [Figure 1]b. [Figure 1]b shows the x and y distance measurement for a two-dimensional (2D) breast size measurement. The three-dimensional volume measurement for PTV was based on the equivalent spherical diameter (ESD) volume, calculated automatically by the Varian Eclipse™ Treatment Planning System. ESD is used to define the volume of irregularly shaped bodies as the diameter of an equivalent volume sphere.[13] Thus, assuming the tumor volume is a cube, its volume is expressed over its diameter.

Regional lymph nodes were not contoured in any patient. The ipsilateral and contralateral lung, contralateral breast, heart, and left anterior descending artery (LAD) were contoured as OARs structures. For dosimetric comparisons of target and OARs doses, Dv, the dose “d” (D2, D50, D98 etc., %/Gy) received by the volume “v” (%/ml) of the selected organ, and Vd, the volume “v” receiving (V5, V20, V25; %/ml) the dose “d” of the selected organ (%/Gy) were calculated separately for each plan. Furthermore, minimum (min) and maximum (max) dose definitions were also recorded.

Radiation therapy planning

All plans were designed using 6 MV photon rays with Trilogy (Varian Medical System, Palo Alto, CA) Eclipse™ Treatment Planning System Version 13.6. VMAT, VMAT-FO, IMRT, IMRT-FO, and 3DCRT applications were created as five different plans.

  1. IMRT: Inverse IMRT planning was performed using five field beams with tangential angles. Gantry angles of 55°, 140°, 160°, 300°, and 320° with a ±5° difference in standard tangential angles were used
  2. IMRT-FO: In the IMRT plan 1 optimization, dose calculations were made over the same dose constraint using the PTV-FO contour
  3. VMAT: Double arc planning was performed at angles of 160°–295°±10° compatible with tangential breast angles. Collimator angles were designed to be 330°–30° for each patient. Double ipsilateral partial arches with a maximum length of 180° starting from the sternum were used. Collimator angles were separately individualized in the range of 15°–30°
  4. VMAT-FO: In VMAT plan 3, the dose calculations were made with the same dose constraint using the PTV-FO contour for optimization
  5. 3DCRT: Tangential gantry angles of 305°–150°±10° that are suitable for internal/external tangential areas were used. The target contour was designed to ensure proper dose distribution with multileaf collimator (MLC) blocks and wedges.

Fifty plans were created by applying five different plans to each of the ten patients. Photon Optimization 13.6.23 and AAA for Volume Dose (Anisotropic Analytical Algorithm 13.6.23) were used to calculate the optimal dose for VMAT and IMRT. Plans were optimized to meet goals and achieve the prescribed dose. A total dose of 50 Gy was prescribed for PTV in a 2 Gy daily fraction. The aim was to deliver at least 95% of the prescribed dose at the planned target, while delivering a homogenous dose at 95%–107% of the defined target dose. The dose-volume constraints used for target and critical structures were established according to our clinical experience, RTOG criteria, and International Commission on Radiation Units and Measurements reports and were kept constant across the plans.[14],[15],[16]

D98, D50, and D2 doses for PTV were calculated via cumulative dose-volume histogram (DVH). Dmax, Dmin, and Dmean values of PTV, calculated automatically by the planning system, were recorded separately for each plan. Patient conformity index (CI) and homogeneity index (HI) values were calculated using the previously defined formulas.[17]

Monitor unit (MU) values, calculated from treatment output, were recorded for comparison between techniques.

Statistical analyses

The distributions of continuous variables were evaluated by the Shapiro–Wilk test. Relationships between the normally distributed variables and technique used were determined using one-way analysis of variance. Between-group differences were analyzed by LSD from post hoc tests. The relationship between breast sizes and indices was evaluated by linear regression analysis. P < 0.05 was considered statistically significant.

 > Results Top

[Figure 2] shows DVH 5 for PTV with beam arrangement and isodose distributions in the same section for a typical patient. Dmin, Dmax, Dmean, HI, and CI values of PTV are given in [Table 1]. While there was no significant relationship between Dmin and Dmax values and techniques, the difference between Dmean values and techniques was significant (P ≤ 0.001, P < 0.05). The Dmax values were highest in VMAT-FO plans, while the lowest values were in the IMRT plan. Pairwise comparisons between groups were performed by multiple comparisons tests. The Dmax value was higher in IMRT-FO plans than in VMAT and VMAT-FO plans (P = 0.067 and P = 0.045, respectively). A significant difference was found between the Dmean values and the plans: VMAT with IMRT (P ≤ 0.001), VMAT with IMRT-FO (P ≤ 0.001), VMAT-FO with IMRT (P ≤ 0.001), VMAT with IMRT-FO (P ≤ 0.001), VMAT-FO with 3DCRT (P = 0.033), IMRT with VMAT (P ≤ 0.001), IMRT with VMAT-FO (P ≤ 0.001), and IMRT with 3DCRT (P ≤ 0.001).
Figure 2: Beam arrangement, isodose distributions, and dose-volume histogram five plan types are shown for a typical patient dose–volume histogram for the planned target volume of all plans (top), beam arrangements and isodose distributions in the same section (bottom)

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Table 1: Comparison of homogeneity index, conformity index, maximum dose, minimum dose, and mean dose

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According to RTOG publications, CI 1 indicates that plan is ideal.[17],[18] When we considered that the CI mean value of plans closest to 1 is the best, the plans' rankings for best CI were VMAT-FO, VMAT, IMRT-FO = IMRT, and 3DCRT (CI: 1.0320, <1.0520, <1.0950 = 1.0950, and <1.4630, respectively). The best CI index plan was VMAT-FO, and the worst plan was 3DCRT. Assuming that the optimal plan for the HI value is closest to zero,[17] the rankings for best HI-based plan were VMAT, VMAT-FO, IMRT, IMRT-FO, and 3DCRT (HI values: 0.0710, <0.0780, <0.0860, <0.0880, and <0.0900, respectively). According to this, VMAT was the best plan with homogeneity, and 3DCRT was the worst plan. For WBI, VMAT plans were considered the best in terms of both CI and HI, while 3DCRT plans were not considered ideal. When CI and HI values were compared for all plans, no significant correlation was found between the plans in terms of HI values. There was a significant correlation between CI and techniques (P < 0.001). This difference was observed between 3DCRT and other techniques.

The results of linear regression analysis between breast sizes and HI, CI, D2, D98, and D50 values are shown in [Table 2]. According to the data, the increase in 2D x-distance and ESD size of the breast significantly explained the increase in CI values (P = 0.006, P = 0.012, respectively). The increase in the x-dimension of the breast and ESD causes deviation from the ideal homogeneous plan. This may be due to a closer relationship between CI and the treatment volume. Additionally, a significant increase in D98 doses was observed in conjunction with the increase in 2D y-distance of the breast and increases in ESD dimensions (P = 0.004 and P = 0.005, respectively).
Table 2: Results of linear regression analysis for the relationship between breast sizes and homogeneity index, conformity index, D2, D98, and D50 values

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Dosimetric parameters of OARs including V5 and V20 of the ipsilateral and contralateral lung, V5 of the heart and contralateral breast, and LAD-max are listed in [Table 3]. When all the plans and OARs doses were compared, heart-V5 (P ≤ 0.001), heart-max (P ≤ 0.001), LAD-max (P = 0.003), ipsilateral-lung-V5 (P ≤ 0.001), ipsilateral-lung-V20 (P = 0.030), and contralateral-breast-V5 (P ≤ 0.001) were significant. Some OAR doses in five different plans are shown in [Figure 3] using a DVH.
Table 3: Comparison of dosimetric parameters of organs at risks for different techniques (mean±standard deviation)

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Figure 3: Dose-volume histograms of the five modalities for a typical patient. Dose-volume histograms of the five modalities for a typical patient are shown for the (a) ipsilateral lung, (b) heart, (c) contralateral lung, and (d) contralateral breast

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When MU values were compared, significant correlations were observed between VMAT and 3DCRT plans and between IMRT and 3DCRT plans (P ≤ 0.001). Likewise, 3DCRT was correlated significantly with both IMRT and both VMAT plans (P ≤ 0.001). Additionally, 3DCRT plans correlated significantly with all plans in terms of MU (P ≤ 0.001). This significant difference between MU values of different planning techniques means that both VMAT plans are conformal and significantly shorten the duration of treatment. The MU values for all plans are shown in [Table 4].
Table 4: Monitor unit values for different plans

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 > Discussion Top

RT is one of the primary treatment modalities prescribed for women diagnosed with breast cancer. RT has been shown to prolong survival, improve local control, and reduce mortality.[19],[20],[21] RT is a critical component of treatment, especially in those with breast conservation surgery.[22] For this purpose, manual forward planning that has been optimized for MLC using field-in-field has also been developed. While this techniques avoids unnecessary higher dose, it is less effective in reducing dose distribution, maintaining homogeneity and confirmity in the target.[23] IMRT was originally developed in the 1990s to preserve normal tissues. Recently, IMRT has been used in many areas, including breast cancer. Despite the theoretical advantage of using IMRT, 3DCRT planning is still preferred in WBI for various reasons.[24],[25],[26] In our study, we found that the ideal plans for CI and HI were both VMAT plans followed by both IMRT plans, whereas 3DCRT was not ideal. Although the 3DCRT contralateral OARs and V5 doses were low, the doses that would produce significant side effects were higher in 3DCRT. Even though data in the literature concerning secondary cancer risk in breast cancer is inconsistent.[27],[28] Incidence of reported RT associated secondary cancers is between 1.2% and 14%.[29] Increase in contralateral breast cancer (CBC) risk in early ages is associated with a positive familial history.[30] In a study comprising 134,501 early stage local btreast cancer risk factors including RT for CBC were evaluated.[29] In a 23-year follow-up process (1973–1996), relative risks for secondary cancer development pertaining to age, race, histological subtype, and use of RT have been determined. 4.2% of the patients (5679) developed secondary cancers. 10- and 20-year follow-ups showed an increase in secondary cancer incidents, which were 6.1% and 12%, respectively. While 3.3% of patients (37379 total) receiving RT developed secondary cancers, this was 4.6% (97,122) for the untreated. In this study, there was no correlation between secondary cancer risk and RT. However, RT has been correlated with a 14% increase in secondary cancer development in a 5-year follow-up. In addition, patients diagnosed before age 45 years had higher cancer risks than those <55. Furthermore, Reiner et al.[31] found no correlation between RT and CBC in patients with BRCA1/2+ variants. They stated that alteration of RT plans of women with breast cancer was unnecessary. In the end, even though there is uncertainty about the correlation between RT and CBC, CBC risk slightly increases in the long term following RT. Therefore, we can recommend VMAT and IMRT plans as first choices for CI, HI, and OARs for WBI. However, considering how respiratory movement lasts long enough to affect the target volume, and RT affects breast volume in conventional plans, MLC jaws terminating adjacent to the breast skin may create uncertainties in the target volume irradiation. In conventional RT applications, adding the FO margin as a gap in the irradiation area can help solve this problem. To compensate for position uncertainties and organ movement in conventional irradiations, a PTV margin is generally added to the target volume. It was noted that a gap margin should be added, taking into account the rapid dose drop zone called “penumbra” at the edge of the PTV.[32] This strategy, which is used in conventional RT planning, has been utilized as “skin flash” IM in IMRT applications for similar purposes in recent years. This structure creation tool has been added as a “skin flash tool” option in some planning systems. By placing the high-dose region very close to the target volume, IMRT reduces the dose of normal structures. This adjacent proximity makes patient or tumor movement more important in techniques such as IMRT and VMAT. When achieving patient motionlessness by immobilizing preventable movements, some precautions are necessary for nonpreventable movements. Although image guidance RT avoids the uncertainty of the target volume between the daily fractions, it cannot prevent organ movements during irradiation in plans such as IMRT where treatment time is long; therefore, a gap should be included in the treatment area to provide a suitable margin.[33] This gap appears to ensure that the target remains within the irradiation site, even if there is movement in the target volume during treatment.

In WBI “skin flash” and “virtual bolus” applications, 20-mm “skin flash” and 10-mm “virtual bolus” in helical tomotherapy were used in IMRT.[34] It was reported that 20-mm “skin flash” and 20-mm “virtual bolus” have the similar effect of increasing surface dose and reducing hot spots in IMRT.[35] The surface dose of the patient's skin was 85%–90% of the defined dose in IMRT plans with the median 6-area by “skin flash” technique. In conventional tangential areas without “skin flash,” the surface dose measured by GAFchromic™ EBT film on the phantom surface was only 45%–65% of the defined dose, whereas, in tangential IMRT and 7-field IMRT plans, the surface dose decreased by 4%–5% and 15%–50%, respectively.[36] Zibold et al.[37] found that the mean WBI surface dose, measured by static phantom and thermoluminescent dosimetry in breast cancer patients, using helical tomotherapy was 80% of the defined dose. Thus, similar results were obtained with different dosimetry systems. Using the “skin flash” technique, the mean surface dose was reported to be relatively higher than in previous studies.[35] In an exemplary patient, the surface doses measured at 0.95 cm were calculated in the range of approximately 92%–95%: VMAT (92.3%), VMAT-FO (93.7%), IMRT (95.3%), and IMRT-FO (93.5%) [Figure 4].
Figure 4: Doses measured on the surface by the treatment planning system. Surface doses measured by treatment planning system for plans volumetric-modulated arc therapy, volumetric-modulated arc therapy-fall-off, intensity-modulated radiotherapy, and intensity-modulated radiotherapy-fall-off

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The option to create “skin flash” is not available in all planning systems, and only IMRT plans permit it when it exists. Moreover, it is a technique that cannot form this structure in all aspects (e.g., from the foreground) of the target volume. The FO margin technique presented here, created by expanding the target volume outwards, can be easily used in all planning systems. When individualized for the patient, it can be designed to be within 2 cm by following the patient's respiratory movements. “Skin flash” technique and “virtual bolus” were commonly used in breast RT to overcome the risk of respiratory failure.[38],[39] Therefore, the FO margin technique is designed to produce a similar effect.

A significant correlation was observed between the breast 2D y-distance and the increase in ESD dimensions with a D98 dose increase. According to the HI calculation formula, the increase in D98 without the change of D2 and D50 brings the HI value closer to zero. This is related to the ideal plan. Conversely, the smaller y-size results in a D98 reduction, which means higher minimum doses. According to the data, the y dimension should not be too small for the ideal WBI plan. The y dimension length in our study was 2.56–9.16 cm, while the x dimension length was 14.37–20.15 cm. IMRT or VMAT planes should be preferred to obtain an ideal plan for very small y-sized and very large x-sized breasts. When evaluating the size of the target volume, a plan preference should be made considering 2D length and especially ESD volume. Additionally, ESD volume can be evaluated as an ideal method for calculating the volume of irregular-shaped lesions.[13]

The lowest MU value was in 3DCRT, while the highest was in IMRT plans. Since MU values are the most important indicators of treatment duration, conformal and VMAT plans significantly shorten the duration of treatment compared to IMRT plans.[6]

A limitation of this study is that no dosimetric equipment was used. Future studies should therefore conduct measurements using such equipment to further confirm our results.

 > Conclusion Top

While trying to achieve the best desired target dose in early-stage breast cancer, the choice of planning technique becomes more complicated with the uncertainties created by organ movements during treatment along with the effort to create the lowest doses for OARs. Plans such as IMRT and VMAT, which are obtained from advanced technological planning progress, are almost routine in battling various cancer types. However, these techniques require longer treatment times, which means more internal organ movement during patient treatments. Furthermore, the millimetric margins used for the lowest OAR dose result in MLC jaws being very close to the breast skin. Additionally, due to respiratory movements and RT-caused breast edema cases, the terminal end of MLC jaws requires a FO margin in terms of irradiated volume. This margin, which has been added to conventional breast irradiation in the past, is now considered on par with methods such as “skin flash” and “virtual bolus.” The more popular “skin flash” technique has the disadvantage of not being applicable to all planning systems and techniques, and it cannot create margins in all directions. In the “virtual bolus” technique, treatment planned with but executed without bolus may cause misleading results in dosimetric values. In summary, the practical FO margin technique is recommended because it is easily applicable to all treatment devices and planning techniques.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patients have given their consent for their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

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  [Figure 1], [Figure 2], [Figure 3], [Figure 4]

  [Table 1], [Table 2], [Table 3], [Table 4]


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