Volumetric changes in lumpectomy cavity during whole breast irradiation after breast conserving surgery

Abhay P Singh; Rahat Hadi; Ashish Singhal; Madhup Rastogi; Rohini Khurana; Shantanu Sapru; Ajeet Kumar Gandhi; Satyajeet Rath; Surendra P Mishra; Anoop Srivastava

doi:10.4103/bjoc.bjoc_23_21

ORIGINAL ARTICLES

Year : 2021 | Volume : 1 | Issue : 2 | Page : 89-94

Volumetric changes in lumpectomy cavity during whole breast irradiation after breast conserving surgery

Abhay P Singh, Rahat Hadi, Ashish Singhal, Madhup Rastogi, Rohini Khurana, Shantanu Sapru, Ajeet Kumar Gandhi, Satyajeet Rath, Surendra P Mishra, Anoop Srivastava
Department of Radiation Oncology, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow, India

Date of Submission	05-Oct-2021
Date of Acceptance	05-Jul-2022
Date of Web Publication	24-Aug-2022

Correspondence Address:
Rahat Hadi
Department of Radiation Oncology, Dr Ram Manohar Lohia Institute of Medical Sciences, Lucknow
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/bjoc.bjoc_23_21

Abstract

Introduction: Irradiation to the conserved breast consists of whole breast radiotherapy (WBRT) followed by tumour bed boost. Seroma in the tumor bed is a commonly observed side effects after breast-preservation, which can alter the shape of breast during WBRT and also lead to tumour bed shrinkage during boost irradiation, causing larger volumes of normal tissue irradiated. The aim was to evaluate the change in the lumpectomy cavity volumes before and after WBRT. Materials and Methods: Thirty-three patients with demonstrable lumpectomy cavity after breast conservation surgery (BCS) were included in the study. CT simulation of the breast was performed twice, initially before the start of WBRT and then 2 days prior to completion of WBRT. WBRT was delivered after contouring breast and lumpectomy volumes guided by the presence of surgical clips, seroma, and other surgical changes. Change in volume of lumpectomy cavity was analysed by Students’ paired T-test. Results: The volume reduction in the lumpectomy cavity was noted in 97% of patients (32/33). The change in lumpectomy cavity volume decreased by a mean value of 34.59% (range 0 - 72%) (p < 0.0001). The mean change in breast volume was 8.44% (range, -2.44 to 10.12%) (p - 0.394). Age, weight, location of tumour, T stage, breast volume, lumpectomy cavity volume, presence of clips and pre-radiation chemotherapy were not significantly associated with volume reduction of the lumpectomy cavity. Conclusion: The results of this study have shown that a significant volume reduction of the lumpectomy cavity after WBRT.

Keywords: Breast conservation surgery, lumpectomy cavity, seroma, volume reduction

How to cite this article:
Singh AP, Hadi R, Singhal A, Rastogi M, Khurana R, Sapru S, Gandhi AK, Rath S, Mishra SP, Srivastava A. Volumetric changes in lumpectomy cavity during whole breast irradiation after breast conserving surgery. Bengal J Cancer 2021;1:89-94

How to cite this URL:
Singh AP, Hadi R, Singhal A, Rastogi M, Khurana R, Sapru S, Gandhi AK, Rath S, Mishra SP, Srivastava A. Volumetric changes in lumpectomy cavity during whole breast irradiation after breast conserving surgery. Bengal J Cancer [serial online] 2021 [cited 2023 Jun 3];1:89-94. Available from: http://www.bengaljcancer.org/text.asp?2021/1/2/89/354409

Introduction

Breast cancer is the second most common cancer in the world and, by far, the most frequent cancer among women with an estimated 2.3 million new cancer cases diagnosed in 2020.^[1],[2] Surgery is considered primary treatment for early-stage breast cancer. Adjuvant treatment for breast cancer is designed to treat micro-metastatic disease and involves radiation therapy and systemic therapy which includes chemotherapeutic, hormonal and biologic agents. The purpose of radiation therapy after breast-conserving surgery is to eradicate local subclinical residual disease while reducing local recurrence rates by approximately 75%.^[3] On the basis of results from several randomized controlled studies, irradiation of the intact breast is considered standard of care, even in the lowest-risk disease with the most favourable prognostic features.^[4] Irradiation to the conserved breast consists of whole breast radiotherapy (WBRT) followed by tumour bed boost. Tumor bed boost by 16 Gray reduced 5 year local recurrence by 3% (from 7.3% to 4.3%), p-0.001, compared to no boost, as reported in an European study.^[5] The 10-year update showed 4% reduction in local recurrence (10.2% to 6.2%)(p < 0.0001).^[6] Seroma in the tumor bed is a commonly observed side effects after breast-preservation, which can alter the shape of breast during WBRT and also lead to tumour bed shrinkage during boost irradiation, causing larger volumes of normal tissue irradiatied. The primary aim was to evaluate the change in the lumpectomy cavity volumes before and after whole breast radiation therapy (WBRT). The secondary aim was to identify factors associated with the change of volume.

Subjects and Methods

The study was a single arm, phase I/II prospective interventional evaluation of post-operative breast cancer patients treated with breast conservation surgery, conducted in a tertiary cancer centre. The minimum accrual planned was that of 30 patients. 33 patients were finally enrolled for the study. Women undergoing breast conserving surgery and WBRT were included in this study. A pre-operative mammography has been done in all patients. CT simulation of the breast was performed twice, the first CT performed before the start of WBRT, and lumpectomy cavity delineated. It was done in spiral mode with no interslice gap, the second CT was performed 2 days prior to completion of WBRT. Breast and lumpectomy volumes were contoured on both CT scans, contouring of the lumpectomy cavities on CT was guided by the presence of surgical clips, seroma, and other surgical changes. The CT planning and delivery of radiation in both WBRT and lumpectomy cavity boost was done according to pre-irradiation CT simulation volume only.

The inclusion criteria was: 18–80 years old female, KPS: 70 and above, pathologically proven diagnosis of early breast cancer, patients must have undergone a breast conservation surgery, after BCS margins should be negative and there must be a demonstrable lumpectomy cavity, no distant metastasis. Patients with residual disease on clinical/radiological examination, concurrent second malignancy and history of previous breast irradiation were excluded from the study.

Treatment was done on Elekta linear accelerator with appropriate energy photons with/without electrons. Recording and verification done by using electronic portal imaging device (EPID) or cone-beam computed tomography (CBCT) for the first 3 fractions and then twice a week. The following factors were assessed for possible corelation: Patient Age (< 50 years Vs. ≥ 50 years), weight (in kg), location (Upper outer quadrant Vs. Others), T stage (T₁ Vs T₂ Vs T₃), breast volume at post-operative scan (in cc), lumpectomy cavity volume (in cc), seroma (present or absent), time elapsed between surgery and radiotherapy (<3 months vs >3 months), Clips (Yes Vs No), pre-radiation chemotherapy (yes vs. no), pre surgery chemotherapy (yes or no).

Statistical analysis

Change in volume of Lumpectomy cavity was analysed by Students’ paired T-test. Paired T-test was applied for percentage mean of difference. For Univariate analysis: all the patients with change in lumpectomy cavity volume were divided in to two groups, change in volume 30% or greater and 60% or greater each group then analysed with variables like age, weight, stage, presence or absence of seroma and breast size.

Calculation of percentage difference of mean by using formula:

Change in co-ordinates of clips was assessed by fusion of pre-WBRT CT set with post WBRT CT set which has been done using same CT setup by verifying fiducial markers and shift in coordinates of clips has been noted. Clips observed and analysed were cranial clips, medial clips, lateral clips and caudal clips pre and post WBRT at x, y and z axis, and further statistical analysis has been done on shifts in co-ordinates of the clips.

Results

Median age was 46 years (range: 32–69). Sixty one percent cases were right lateral breast cancers. Most of the patients were having tumor in upper quadrants (69.7%), the distribution was: upper inner quadrant – 12, upper outer quadrant – 11, central – 4, lower inner quadrant – 4, lower outer quadrant – 2. Twelve cases (36.4%) received neo-adjuvant chemotherapy (NACT). Nine patients (27%) received Epirubicin and Cyclophosphamide as NACT while 4 patients (12%) received 5-flurouracil, Epirubicin and cyclophosphamide as NACT. Seroma and clips were found in 39% and 56% of patients, respectively as shown in [Figure 1] [Table 1].

Figure 1: 13, Seroma was present in 13 Patients (39%), 18 patients were with surgical clips and all patients were having pre-operative mammogram.

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Table 1: The details of post-operative histopathology staging and pathological features are provided in table 1

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Volumetric changes in the lumpectomy cavity and breast after whole breast irradiation

The volume reduction in the lumpectomy cavity was noted in 97% of patients (32/33). The mean volume of the lumpectomy cavity before and after WBRT were 74.78 cc (range 23.64 - 376.73) and 47.00 cc (range 14.56 - 200.22), respectively. The lumpectomy cavity volume decreased by a mean value of 34.59% (0 - 72%) (p < 0.0001) and median value of 35.43%. The mean breast volumes before and after WBRT were 909.56 cc and 905.05 cc, respectively, representing a mean change of 8.44% (range, -2.44 to 10.12%) (p - 0.394) and median change of 7.45 cc [Table 2].

Table 2: Volumetric changes in lumpectomy cavity and breast volume during WBRT

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Factors associated with lumpectomy cavity volume change

On univariate analysis, only the presence of seroma at the initiation of WBRT was significantly associated with a volume reduction in the lumpectomy cavity of 30% or greater and not with volume reduction 60% or greater (p - 0.015, for ≥30% adjusted R squared-0.148; p - 0.220, for ≥ 60% adjusted R squared - 0.017). Age, weight, location of tumour, T stage, breast volume, lumpectomy cavity volume, presence of clips and pre-radiation chemotherapy were not significantly associated with volume reduction of the lumpectomy cavity [Table 3].

Table 3: Univariate analysis of factors affecting the change in volume of the lumpectomy cavity

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Change in co-ordinates of surgical clips pre & post rt: paired t-test results

Clips observed and analysed: Cranial, medial, lateral and caudal clips pre and post WBRT at x, y and z axis [Table 4]. Shift in co-ordinates of all clips on x axis by mean value of 0.71cm, median - 0.62, SD - 0.940. Shift in co-ordinate of all clip on y axis by mean value of 0.44 cm, median - 0.20, SD - 0.892. Shift in co-ordinate of all clips on z axis by mean value of 0.58 cm, median - 0.34, SD - 0.907.

Table 4: Change in coordinates of surgical clips pre- and post-WBRT

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Discussion

Amongst all the randomised trials assessing role of radiotherapy boost, surgical clips were used in all patients for assessing boost volume only in the Budapest trial.^[7],[8] In other studies, the boost volumes were usually defined on clinical and surgical details. It was hypothesized that increasing differences between local failure rates in whole breast radiotherapy (WBRT) arm versus WBRT boost arm in Lyon trial (4.5% vs. 3.6%),^[9] EORTC trial (10.2% vs. 6.2%)^[5] and Budapest trial (15.5% vs. 6.7%)^[7],[8] may well have been due to the different techniques of tumour bed delineation as the difference in boost doses between all these trials were not significantly different. Hence an accurate delineation of tumour bed is important as it may translate into improved local control rates.

In the institutions not having facilities to objectively define lumpectomy cavity, preoperative clinical description like patients’ perception of tumour position, preoperative clinical photographs, tattoos over tumour, mammographic findings and surgical notes forms the basis of boost field definition. These techniques are however subjective and might be inaccurate in many scenarios. Boost volumes defined by clinical description were found to be inadequate in almost 10.88% of cases when compared with lumpectomy bed delineated by surgical clips.^[10] The surgical scar could be of great help, but it has been observed that in most instances the lumpectomy scar is not necessarily directly related to the site of the tumour. Tumour bed defined by surgical scar may lead to geographical miss resulting in increased local failure rates and also may result in unnecessary irradiation of normal tissue volume.^[10]

Since the time breast conserving surgery came to the fore, the adequate number and position of surgical clips required for postoperative radiotherapy has been a matter of debate. They are generally placed at four corners and in the tumour bed although the placement of surgical clips and their number may vary. The clinically defined fields have shown inadequate coverage in 42–68% of patients when compared with position of clips.^[11],[12] The depth of lumpectomy cavity has been found to be most accurately assessed by surgical clips placed within tumour bed.^[12] Also, increasing the margins to field by 3 cms in order to ensure coverage of lumpectomy cavity resulted in 25% breast tissues at low risk to be treated to an extra dose.^[12] With increasing gap between surgery and radiotherapy due to addition of chemotherapy issues like changes in the lumpectomy cavity and resultant clip displacement came into picture. To calculate the mean displacement of clips, Weed et al.^[13] compared images in CT scans done at an interval of 27 days. They found that there was a mean displacement of clips by 3 mm in all 3 co-ordinates which can be easily covered by a margin of 5 mm usually given for Clinical target volume (CTV) demarcation. In our study shift in coordinates were 7 mm,4.4 mm and 5.8 mm in x,y and z- axis, respectively.

For delineation of lumpectomy cavity CT scans alone or in combination with surgical clips have been found to be fairly accurate in determining the tumour bed. The chief advantages of CT scan include better visualization in early postoperative period and an obvious sparing of normal breast tissues at low risk seen as much as in 50% of cases. The disadvantage of CT is its difficulty to distinguish glandular breast tissues from surrounding anatomy. Due to the hypothesized poorer images it was thought that ultrasound has a greater accuracy in defining boost fields as well as depth of prescription. But, a random comparison of lumpectomy cavity delineated for electron boost planning by CT and US showed nearly identical dimensions and margins with both the techniques. In our study lumpectomy cavity delineation was done with the help of CT scans, surgical clips, pre-operative clinical findings, preoperative mammogram, post-operative changes like seroma / hematoma and surgical scars. In our analysis seroma was present in 39% (13/33) cases, surgical clips were present in 56% patients, about 15% patients were having both the surgical clips and seroma.

For the maximum local tumor control, boost irradiation field should accurately encompass the lumpectomy cavity volume,^[5],[6],[9] although the technique of delivering the boost is not standardized. From 10 to 67% of scar based boost plans were inaccurate in defining the boost volume if compared with surgical clip based plans.^{[10],[12],[14]} And 70 to 80% of scar based plans shows a geographical misses or modifications when compared with CT based plans.^{[15],[16],[17]} Boost irradiation is delivered immediately after WBRT. In most of the centres, single CT simulation done 5 to 7 weeks before the boost RT simulation is used to delineate the lumpectomy cavity. However, dynamic processes of complex tissue remodelling and healing both before and during the course of WBRT are occurring within the lumpectomy cavity. These changes are account for significant reduction of the lumpectomy cavity volume, which may lead to the geographical misses or excessive normal tissue irradiation if single CT scans done before the course of WBRT are used for the boost planning.^{[13],[17],[18],[19],[20],[21]}

Oh et al. and others reported mean volume reduction in the lumpectomy cavity after WBRT between 22.5 to 64%.^{[19],[20],[22],[23]} Volume reduction in the lumpectomy cavity in our study was noted in 97% of patients (32/33). The mean volume of the lumpectomy cavity before and after WBRT were 74.78 cc and 47.00 cc, respectively. The lumpectomy cavity volume decreased by a mean value of 34.59% (0 to 72%) (p<0.0001) and median value of 35.43%. The mean breast volumes before and after WBRT were 909.56 cc and 905.05 cc, respectively, representing a mean change of 8.44% (range, -2.44 to 10.12%)(p = 0.394) and median change of 7.45 cc.

In our analysis the presence of seroma at the initiation of WBRT was significantly associated with a volume reduction in the lumpectomy cavity of 30% or greater and not with volume reduction 60% or greater (p = 0.015, for ≥30%, adjusted R squared-0.148; p - 0.220, for ≥60% adjusted R squared-0.017). Age, weight, location of tumour, T stage, breast volume, lumpectomy cavity volume, presence of clips and pre-radiation chemotherapy were not significantly associated with volume reduction of the lumpectomy cavity. The volume of breast was not significantly changed during WBRT in our analysis (p = 0.394). Hepel et al.^[17] reported a mean volume reduction in the lumpectomy cavity during the course of WBRT of 52% and they attributed volume reduction to a decrease in postoperative seroma size. However, many other investigators^[22],[23] including our data demonstrated significant volume reduction in the lumpectomy cavity in patients who had no seroma during the course of WBRT. While Tersteeg et al.^[19] found a linear correlation between lumpectomy cavity volume and the reduction of absolute volume, Hepel et al.^[17] observed that initial lumpectomy cavity of >15 cc had greater likelihood of a decrease in volume. Flannery et al.^[20] suggested repeating CT simulation in cases with cavity volume more than 30 cc. Unlike others, Prendergast et al.^[23] did not observe corelation between the volume of the lumpectomy cavity and the reduction. The presence of seroma significantly induced extensive volumetric reduction during WBRT in this study and these changes could have an impact on the accuracy of boost irradiation planning. Significant volume reduction in the lumpectomy cavity may also be of concern when boost irradiation is based on the initial CT simulation before WBRT.

Lumpectomy cavity boost using simultaneous integrated boost (SIB) technique which is irradiating tumor bed to a higher differential dose from first day of treatment has also been reported.^{[24],[25],[26]} One disadvantage as pointed out by Sharma et al.^[27] is that irradiates unnecessary normal tissue as the lumpectomy cavity shrinks continuously during treatment.

Conclusion

The results of this study have shown that a significant volume reduction of the lumpectomy cavity after WBRT. A significant correlation was observed between the presence of seroma and the volume reduction.

Acknowledgement

None.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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