Practice of Tumor Bed Boost in Patients after Oncoplastic Breast-Conserving Surgery

Abstract

The practice of boost to the tumor bed after treatment with oncoplastic breast-conserving surgery (BCS) remains variable. Using a survey, the present study evaluated the current practice of tumor bed boost administered in women after oncoplastic BCS. Actively practicing radiation oncologists across India were sent a questionnaire on the practice of adjuvant whole-breast radiotherapy and tumor bed boost after oncoplastic BCS via email and encouraged to participate. Of the 54 radiation oncologists who participated, most (98.1%) used a linear accelerator for radiotherapy. Hypofractionation was preferred by 59.26%, standard fractionation by 7.41%, and the remaining selected the fractionation strategy based on various patient factors. In addition, 83.33% participants reported that they always planned tumor boost, 51.85% preferred photons for the boost, and 75.93% administered sequential boost. The most common dose for the boost was 12.5 Gy in five fractions (40.74%). Most participants (77.78%) revealed that they used a combination of methods for identifying the tumor bed. With respect to clip placement, most surgeons (96%) at the participants’ centers placed ≥ 4 clips at the tumor site, with both the base and margins being preferred by surgeons (81.48%) for placement. Finally, 12.96% participants revealed that the surgeons always involved them during surgical planning, whereas 7.4% participants reported that they always included the surgeons during radiotherapy planning, suggesting that radiation oncologists and oncoplastic surgeons do not involve each other during surgical and radiotherapy planning, possibly leading to suboptimal treatment. This may be attributed to the absence of guidelines regarding boost practices after oncoplastic BCS.

Introduction

Breast cancer, the most common malignancy among women (24.5%) worldwide, is the leading cause (15.5%) of cancer-related death [1]. Breast-conserving therapy and mastectomy are the two main strategies of breast cancer treatment. Randomized controlled trials have consistently demonstrated that both strategies are comparable with regard to the rates of local control and survival in women with early-stage breast cancer [2, 3].

Although breast-conserving surgery (BCS) is an important treatment option, it is important to note that in a considerable proportion of cases (20%–30%), tumor excision can lead to breast deformity, thereby impacting the cosmetic outcome [4]. Oncoplastic BCS, which addresses this challenge, combines tumor removal with complete surgical margins and plastic reconstruction techniques to preserve the breast with its natural shape and appearance, thereby offering optimal cosmetic and oncologic outcomes [5]. Clough et al. [5] described two levels of oncoplastic BCS procedures according to the volume of resected breast tissue: level 1 refers to < 20% volume resection and level 2 indicates > 20% resection. The various effective surgical treatment options have enabled individualized care to optimize treatment outcomes in women with breast cancer.

Breast-conserving therapy involves a two-step process of BCS, followed by radiation to the whole breast. Adjuvant radiation therapy typically comprises of 4–5 weeks of whole-breast radiation (40–50 Gy) and may optionally include a radiation boost to the tumor bed [6]. Boost implies additional doses of radiation administered at the initial tumor site, which is most commonly delivered after completing whole-breast radiation and sometimes simultaneously as part of a simultaneous integrated boost (SIB). It has been shown that 44%–90% of local recurrences originate from the residual microscopic tumor cells in the tumor bed [7–9]. A boost to the tumor bed reduces recurrence by eliminating these residual cells [10, 11]. The administration of a radiation boost is not universally applied in all cases because of several considerations, including the potential for increased adverse events, tumor grade, and availability of technology. In addition, the administration of boost can result in higher treatment costs, longer treatment periods, and poor cosmetic outcomes in some cases [6].

Various factors, including age, margin status, vascular invasion, node positivity, and intraductal involvement, play a crucial role in determining the appropriate dose and type of radiation therapy and have been identified as important in recurrence risk assessment [12]. Thus, the need to tailor radiotherapy to individual patients based on these factors has resulted in a lack of standardization regarding the optimal dosage for radiation to the entire breast and boost to the tumor bed.

To reduce recurrence risk and address the likely fibrosis, the administration of a boost during radiation therapy requires careful definition of the optimal boost volume [13]. Various methods, including preoperative images, surgical scars, seroma, and surgical clips, are utilized to delineate the tumor bed for accurately determining the ideal boost volume [13]. However, after oncoplastic BCS, none of these methods can be relied upon solely because of the altered anatomy resulting from pillar mobilization or flap insertion in the treated breast. In oncoplastic BCS, where the tumor bed is displaced, there is uncertainty regarding the method employed by radiation oncologists to identify the precise site of the tumor bed. In this context, there are no established guidelines on the optimal method of tumor bed identification, and there is variation in the practice of administering radiation boost following whole-breast radiation in patients treated with oncoplastic BCS. Thus, this study assessed the current practice of boost to the tumor bed in Indian patients after undergoing oncoplastic BCS.

Methods

This study was conducted from November to December 2021 using an online cross-sectional questionnaire, which was sent electronically to practicing radiation oncologists in the country. The questionnaire was formulated based on common clinical scenarios and a comprehensive literature review on oncoplastic BCS in relation with radiotherapy. The literature review revealed three main areas of discussion: a) the necessity, number, and location of intraoperative surgical clip placement; b) whether radiation oncologists and oncoplastic surgeons agree with regard to the accurate tumor bed identification for boost after oncoplastic surgery; and c) involvement of oncoplastic surgeons during radiation planning.

The survey pertained to whole-breast radiation and tumor bed boost along with radiotherapy planning after oncoplastic BCS. The questionnaire inquired the type, dose, and delivery of the initial whole-breast radiation and site and dose of tumor bed boost in patients after BCS. Further, the questionnaire was designed to understand whether there is shared decision-making between radiation oncologists and oncoplastic surgeons while planning surgical treatment and evaluating the site of tumor bed boost. Table 1 lists the questions asked in the online survey. The responses were analyzed using descriptive statistics on Microsoft Excel 2016.

Table 1.

Survey data

Sr. no	Information	Responses
1	Center type	Government institute (15/54 [27.78%]) Private/corporate institute (31/54 [57.41%]) Trust (8/54 [14.81%])
2	Whether oncoplastic breast-conserving surgeries are performed at the participant’s center	Yes (50/54 [92.59%]) No (4/54 [7.41%])
3	Number of oncoplastic breast-conserving surgeries performed at the participant’s center per year	1–20 (17/50 [34%]) 21–50 (14/50 [28%])  > 50 (19/50 [38%])
4	Radiotherapy machine type	Cobalt (0/54 [0%]) Linear accelerator (53/54 [98.15%]) Proton (1/54 [1.85%])
5	Type of dose-fractionation employed for whole-breast external beam radiotherapy	Standard fractionation (4/54 [7.41%]) Hypofractionation (32/54 [59.26%]) Both depending on the patient profile and other factors (18/54 [33.33%])
6	Dose fraction employed for whole-breast radiotherapy	50 Gy in 25 fractions (7/54 [12.96%]) 40 Gy in 15 fractions (39/54 [70.03%]) 42.5 Gy in 16 fractions (5/54 [9.26%]) 26 Gy in 5 fractions (4/54 [7.4%])
7	Whether tumor bed boost is planned for all patients after breast-conserving surgery	Yes, for all patients (45/54 [83.33%]) Yes, for some patients (based on high-risk features) (9/54 [16.67%])
8	Molecule used for tumor bed boost delivery	Electron (14/54 [25.93%]) Photon (28/54 [51.85%]) Proton (1/54 [1.85%]) Photons and electrons (11/54 [20.37%])
9	Dose fraction employed for tumor bed boost	12.5 Gy in 5 fractions (22/54 [40.74%]) 10 Gy in 5 fractions (13/54 [24.07%]) Others (10/4; 12/4; 12/6; 15/5; 16/6) (19/54 [35.19%])
10	Method used for tumor bed boost delivery	Sequential (41/54 [75.93%]) Simultaneous integrated boost (13/54 [24.07%])
11	Biologically effective dose administered at the tumor bed	85–94 Gy (13/54 [24.07%]) 95–104 Gy (37/54 [68.52%]) 105–114 Gy (4/54 [7.4%])
12	Method used to identify the tumor bed	Presurgical imaging (2/54 [3.7%]) Surgical clips used intraoperatively to mark the tumor bed (10/54 [18.52%]) Seroma cavity (0/54 [0%]) Surgical scar (0/54 [0%]) Combination of the above options (42/54 [77.78%])
13	Whether oncoplastic surgeons at the participant’s center place surgical clips at the tumor bed site	Yes (50/54 [92.59%]) No (4/54 [7.41%])
14	Minimum clips placed by surgeons for tumor bed localization	2 (2/50 [4%]) 4 (25/50 [50%]) 5 (14/50 [28%]) 6 (9/50 [18%])
15	Location of the surgical clip placement	Only base (3/50 [6%]) Base and margins (44/50 [88%]) Only margins (2/50 [4%]) NA (1/50 [2%])
16	Whether the patient is reimaged prior to tumor bed boost planning	Yes (10/54 [18.52%]) No (39/54 [72.22%]) Maybe (5/54 [9.26%])
17	Whether oncoplastic surgeons include the participant in the decision-making team for combined decision prior to treatment	Yes, always (7/54 [12.96%]) Yes, on a case-to-case basis (31/54 [57.41%]) No, never (15/54 [27.78%]) NA (1/54 [1.85%])
18	Whether the participant includes oncoplastic surgeons in the decision-making process during tumor bed boost planning	Yes, always (4/54 [7.4%]) Yes, on a case-to-case basis (41/54 [75.93%]) No, never (9/54 [16.67%])

Results

In total, 54 radiation oncologists practicing in different parts of the country responded to the questionnaire. Table 1 presents the responses to the survey. Of the 54, 31 (57.41%) radiation oncologists practiced at private/corporate institutions, 15 (27.78%) at government institutions, and 8 (14.81%) at trust-run institutions. The survey revealed that oncoplastic BCS is commonly performed at 50 (92.59%) of the 54 participants’ centers. Of these 50 centers, 19 (38%) performed > 50 surgeries, 14 (28%) performed 21–50 surgeries, and 17 (34%) performed 1–20 surgeries annually.

Nearly all radiation oncologists (n = 53; 98.1%) who participated in this study delivered radiotherapy using a linear accelerator, whereas only one participant reported using a proton-based device and none used a cobalt-based device. More than half (n = 32; 59.26%) of the participants utilized hypofractionation, 4 (7.41%) used standard fractionation, and 18 (33.33%) employed both hypofractionation and standard fractionation for external beam radiotherapy to the whole breast. With regard to the dose fraction employed for radiotherapy to the whole breast, most reported 40 Gy in 15 fractions (n = 38; 70.03%), followed by 50 Gy in 25 fractions (n = 7; 12.96%), 42.5 Gy in 16 fractions (n = 5; 9.26%), and 26 Gy in 5 fractions (n = 4; 7.4%).

A high proportion of radiation oncologists (n = 45; 83.33%) always planned tumor bed boost for patients after BCS, whereas the remaining (n = 9; 16.67%) planned the boost based on high-risk features such as nodal involvement, pathological tumor size, margin status, and lymphovascular invasion. Regarding the method employed for tumor bed boost delivery, 28 radiation oncologists (51.85%) used photons, 14 (25.93%) used electrons, 11 (20.37%) used both photons and electrons, and 1 (1.85%) used protons. Meanwhile, 41 (75.93%) participants administered sequential boost, whereas 13 (24.07%) performed SIB. The most common dose for tumor bed boost administered by the participating radiation oncologists was 12.5 Gy in 5 fractions (n = 22; 40.74%), followed by 10 Gy in 5 fractions (n = 13; 24.07%); the remaining (n = 19; 35.19%) used 10 Gy in 4 fractions, 12 in 4, 12 in 6, 15 in 5, and 16 in 6. As the participants reported using the sequential or SIB technique, the dose values were converted to biologically effective dose (BED; α/β = 3) for the easy comparison of total radiation administered to the tumor bed. The conversion showed that 13 radiation oncologists administered 85–94 Gy, 37 administered 95–104 Gy, and 4 administered 105–114 Gy BED.

During the survey, participants provided insights into how they identified the tumor bed for boost after oncoplastic BCS. The responses indicated diverse approaches: 2 participants (3.7%) relied on presurgical imaging, 10 (18.52%) used surgical clips, and 42 (77.78%) utilized a combination of presurgical imaging, surgical clips, seroma cavity, and surgical scar for identification. Of note, most participants (n = 50; 92.59%) reported that oncoplastic surgeons at their centers placed surgical clips at the tumor site, suggesting a common practice. Among the participants, 25 (50%) reported the placement of 4 surgical clips, 2 (4%) mentioned 2 clips, 14 (28%) indicated 5 clips, and 9 (18%) stated 6 clips. Regarding the location of clip placement, 44 (88%) participants mentioned clips being placed on the base and margins of the excision cavity, followed by 3 (6%) and 2 (4%) who reported placement on the base alone and margins alone, respectively; 1 (2%) participant did not specify the location. In terms of reimaging patients prior to the boost, the responses varied. A significant portion of participants (n = 39; 72.22%) stated that they do not reimage patients. By contrast, 10 (18.52%) participants always reimaged patients and 5 (9.26%) reimaged patients on an individual basis.

With regard to shared decision-making among oncoplastic surgeons and radiation oncologists prior to treatment, 31 (57.41%) reported that oncoplastic surgeons included them in the treatment decision-making team on a case-to-case basis, indicating a collaborative approach. Seven participants (12.96%) mentioned that the surgeons discussed all cases with them, indicating a higher level of involvement. Finally, three-fourths (n = 41; 75.93%) of the participants reported that they involved oncoplastic surgeons during tumor bed boost planning on a case-to-case basis, whereas 7.4% and 16.67%, respectively, always and never involved the surgeon.

Discussion

Numerous randomized clinical trials conducted since the late 1970s have consistently demonstrated the comparable effectiveness of mastectomy and BCS with radiotherapy [14]. Radiotherapy administered after BCS includes radiation to the whole breast, followed by an optional boost to the tumor bed [6]. However, the optimal radiation dose for boost delivered to the tumor bed after whole-breast radiation remains uncertain. The National Comprehensive Cancer Network recommends 10–16 Gy of boost via external beam radiotherapy or interstitial brachytherapy in women with an increased risk of recurrence [15]. However, European guidelines suggest a tumor bed boost in women who exhibit at least one of the following factors: age ≤ 50 years, grade 3 tumors, vascular invasion, extensive ductal carcinoma in situ, and cases of nonradical tumor excision [16]. A retrospective study on data from 18 centers based in the US, Israel, Australia, and Europe revealed that 65% patients received a 10-Gy boost, 27% received > 10 Gy, and 8% received < 10 Gy [17], suggesting a lack in the universal practice of boost to the tumor bed.

A randomized trial demonstrated that an additional 16-Gy boost administered to the tumor bed reduced the risk of tumor recurrence in the ipsilateral breast, particularly in younger patients [10]. Vrieling et al. revealed a beneficial effect of additional boost in patients aged < 50 years and in those with tumors of high grade and negative estrogen receptor, whereas the boost was not beneficial in older patients with low-grade estrogen receptor-positive tumors [12]. Moreover, boost administration reduced the incidence tumor recurrence in the ipsilateral breast to 2% at 5 years [18]. Local control improves with a tumor bed boost, according to a recent Cochrane review, although overall survival and disease-free survival do not differ [6]. The use of boost was suggested for women aged < 50 years with extensive intraductal involvement and positive/close surgical margins [19]. Bahadur et al. [20] found that cosmesis was worse in women who received tumor bed boost, highlighting a potential downside irrespective of age. However, Collette et al. [21] clarified that the adverse effects of the boost were not age-dependent, dispelling the notion that younger patients face a higher risk. Thus, a tumor bed boost after BCS may improve survival, particularly in young patients, with better cosmesis.

The success of boost to the tumor bed after whole-breast radiation relies on accurately defining and locating the tumor bed. However, oncoplastic BCS can cause tissue rearrangements, making it challenging to identify the tumor bed [22]. Various methods are used to estimate the localization of the tumor bed: surgical scar, surgical clips, seroma cavity, and presurgical computed tomography images. While surgical scars can be used when it is present over the tumor site, incisions made during oncoplastic approaches may not accurately indicate the tumor bed location. The seroma cavity, visualized through computed tomography, is another method, but it represents breast reconstruction rather than the tumor removal defect. Oncoplastic BCS can also result positioning changes in the nipple–areola complex, tumor bed shifts, and cavity alterations [23–25]. Surgical clips along with computed tomography images are useful for visualizing the tumor bed [26, 27]. However, a survey study indicated that not all surgeons routinely place surgical clips (only a third of the surgeons place clips) and that 38.7% radiation oncologists delivered boost only when clips were placed while 34.6% radiation oncologists delivered boost regardless of clip placement [28]. Moreover, different studies have recommended different optimal number of clips for tumor bed marking [25, 29, 30]. Nevertheless, clips have limitations as they mark only individual points in the bed, requiring interpolation to define the borders [31]. Moreover, they can be displaced during treatment and may be placed by surgeons for hemostasis, leading to the incorrect estimation of the bed [25, 32]. Thus, the standard methods of tumor bed identification, in isolation, are inadequate after oncoplastic BCS, and the challenges in localization may result in the nonapplication of boost treatment.

The present study aimed to assess the variability in tumor bed boost practices, including dose and identification methods, in patients undergoing oncoplastic BCS in India. An online questionnaire was sent to radiation oncologists to gather information on the tumor bed identification method, actual radiation dose administered (both whole-breast radiation and tumor bed boost), type of device and molecule used for radiation, and collaborative involvement of both radiation oncologists and surgeons during surgical and radiation treatment planning. The results indicated that nearly all radiation oncologists (98.15%) administered whole-breast external beam radiotherapy using a linear accelerator with more than half of them (59.26%) preferring hypofractionation. Conventional fractionation has been the standard approach for adjuvant whole-breast radiation following BCS for over four decades [33]. Nevertheless, studies have shown that moderate hypofractionation (40–42.5 Gy/15–16 fractions) is as effective as conventional fractionation while offering improved acute tolerance [34, 35]. A recent trial demonstrated that hypofractionated radiation with a 40-Gy dose was not inferior to the standard 50-Gy dose in terms of recurrence and 9-year overall survival, with improved cosmesis and patient satisfaction in the 40-Gy group [36]. Brunt et al. [37] revealed that 26 Gy/5 fractions and 40 Gy/15 fractions had similar 5-year recurrence risk outcomes. However, not all participants in our survey adopted hypofractionation and only one-third of them based the fractionation dose on patient profiles and other factors.

Nearly all radiation oncologists who participated in our survey revealed that they administered radiation via photons and/or electrons (98.15%), whereas only one participant administered protons. Although several studies have revealed that proton-based radiation leads to lower mean doses to the heart than other molecule-based radiation [38–40], proton radiotherapy is expensive and not accessible to all patients. Moreover, studies have shown that proton-based radiotherapy was not associated with increased overall survival, was not cost effective, and only those undergoing left-sided internal mammary lymph node radiation, which is associated with mean doses of > 5 Gy to the heart, may benefit from protons, albeit at a higher cost [41, 42]. These studies suggest that photons/electrons, which were used by almost all participants in our survey, are preferable to protons in terms of the cost to benefit ratio.

The 2014 joint guidelines of the Society of Surgical Oncology (SSO) and American Society for Radiation Oncology (ASTRO) recommended that boost to the tumor bed in margin-negative patients (no tumor ink) should be based on a prior estimation of the risk of local failure and not on the width of the surgical margin [43]. A subsequent time trend analysis by Tom et al. [44] found a reduction in the administration of boost to the tumor bed in patients with negative margins following the publication of the 2014 SSO-ASTRO guidelines. However, in our survey, it was unclear whether the participating radiation oncologists performed bed boosts after confirming the resection margins, despite 83.33% of them routinely performing bed boosts.

In terms of boost techniques, SIB has several advantages over sequential boost, including shorter treatment duration, better dose distribution, and multiple subsite simultaneous irradiation [45, 46]. However, our survey revealed that 75.93% of the participants still used the sequential boost technique, which extends treatment duration and provides inferior dose distribution compared to SIB.

Tumor bed identification after oncoplastic BCS is crucial for planning an optimal tumor bed boost. In our survey, 77.78% of participants used a combination of methods, including presurgical imaging, surgical clips and scar, and seroma cavity. In particular, 3.7% and 18.52% used only presurgical imaging and only surgical clips, respectively. However, 72.22% of the participants replied that they do not reimage the patients prior to the boost, which may reduce unnecessary radiation and costs but may lead to poor data for bed identification. Surgical clips were placed at the tumor bed by oncoplastic surgeons at 92.59% of centers, with the placement of ≥ 4 clips being most common. These findings highlight the importance of using multiple methods to identify the tumor bed and plan the boost owing to the limitations of each individual method. The use of Biozorb® three-dimensional bioabsorbable tissue marker has been proposed as an alternative tool with potential benefits in reducing planned target volumes and achieving good cosmetic outcomes, but its impact on oncologic outcomes and recurrence rates remains unknown [47].

The survey findings indicated a significant lack of collaboration and communication between oncoplastic surgeons and radiation oncologists in the treatment decision-making process and planning of the tumor bed boost. Only 12.96% of participants were actively included by the oncoplastic surgeon in their treatment decision-making team, while 57.41% were included on a case-to-case basis and 27.78% were never consulted. Likewise, when planning the boost, only 7.4% always involved the oncoplastic surgeon, 75.93% did so on a case-to-case basis, and 16.67% never consulted the surgeon. This is particularly concerning given the complex nature of oncoplastic BCS, which involves tissue shifting and tumor bed displacement. Traditional methods such as relying solely on the seroma cavity and surgical clips may not be effective after tissue displacement. Thus, it is essential for radiation oncologists to receive a detailed surgical procedure report that provides crucial information on how the tumor bed may have been moved from its original position, along with the precise location of surgical clips and preoperative computed tomography images. In this context, a close discussion and collaboration between radiation oncologists and surgeons is critical.

There are certain limitations to the study. First, as this was a cross-sectional survey, time trends regarding the practice of bed boost after oncoplastic BCS in India could not be determined. Second, patient factors influencing boost administration and fractionation dose selection were not captured. Third, the evaluation of resection margins by participants who always administered the boost remains unknown.

Conclusion

The survey shed light on the preferences of radiation oncologists in India for boost administration. The cross-sectional electronic questionnaire survey revealed that radiation oncologists in India favored using a photon/electron-based linear accelerator while employing various methods to identify the tumor bed. Moreover, over half of the participants chose hypofractionated whole-breast radiation.

A significant finding was the lack of consistent consultation between radiation oncologists and oncoplastic surgeons during surgical treatment and radiotherapy planning. This poses challenges as oncoplastic surgery involves tissue rearrangement, making tumor bed identification and the subsequent boost administration difficult. Therefore, involving both the oncoplastic surgeon and radiation oncologist in surgical planning as well as in the subsequent radiotherapy and boost volume planning is recommended.

Data Availability

All data supporting the findings of this study are available within the paper.

Declarations

Conflicts of Interest

The authors declare that they have no conflict of interest.