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Breast Reconstruction and Radiation Therapy: An Update

Nelson, Jonas A. MD; Disa, Joseph J. MD

Plastic and Reconstructive Surgery: November 2017 - Volume 140 - Issue 5S - p 60S-68S
doi: 10.1097/PRS.0000000000003943
Original Articles
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Summary: With the indications for radiation therapy in the treatment of breast cancer continuing to expand, many patients present for reconstruction having previously had radiation or having a high likelihood of requiring radiation following mastectomy. Both situations are challenging for the plastic surgeon, with different variables impacting the surgical outcome. To date, multiple studies have been performed examining prosthetic and autologous reconstruction in this setting. The purpose of this article was to provide a general platform for understanding the literature as it relates to reconstruction and radiation through an examination of recent systematic reviews and relevant recent publications. We examined this with a focus on the timing of the radiation, and within this context, examined the data from the traditional surgical outcomes standpoint as well as from a patient-reported outcomes perspective. The data provided within will aid in patient counseling and the informed consent process.

New York, N.Y.

From the Memorial Sloan Kettering Cancer Center, Plastic and Reconstructive Surgery Service.

Received for publication June 27, 2017; accepted August 17, 2017.

Disclosure: Neither of the authors has any conflicts of interest to report. No funding was received.

Joseph J. Disa, MD, Memorial Sloan Kettering Cancer Center, Plastic and Reconstructive Surgery Service, 1275 York Ave, New York, NY 10065, Disaj@mskcc.org

As breast conserving therapy (BCT) has similar survival benefit compared with mastectomy when appropriately utilized,1–4 the majority of eligible women opt for this option as it has demonstrated superior psychosocial results.5 However, a small portion of women who undergo BCT experience a locoregional recurrence ultimately requiring salvage mastectomy.6–8

Additionally, the indications for postmastectomy radiation therapy (PMRT) are expanding. Although the American College of Radiology currently recommends radiation for tumors greater than 5 cm or > 4 involved lymph nodes,9,10 PMRT is often applied more broadly, given its benefit in preventing local recurrence,11 especially given the National Comprehensive Cancer Network’s recommendation to expand PMRT to patients with tumors 5 cm or smaller and 1–3 positive nodes.12

Although BCT is the central component of surgical breast cancer treatment, recent population-based studies have demonstrated increasing rates of mastectomies.13 Associated with this trend is an increase in immediate breast reconstruction (IBR) rates,14,15 which is related to utilization of implant-based modalities.14,15 Interestingly, although patients who need PMRT are less likely to undergo IBR,14,16 this cohort has seen recent increases in IBR overall.16,17 This increase appears to again be isolated to implant-based modalities, which are now the most common modality in these patients.16,17

Both premastectomy and PMRT present a significant challenge for the reconstructive surgeon. The purpose of this article was to provide an understanding of the literature as it relates to breast reconstruction and radiation with an examination of recent systematic reviews and relevant publications. We will focus on the timing of the radiation and will examine the data from the traditional surgical outcomes standpoint as well as from a patient-reported outcomes perspective.

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EFFECT OF RADIATION ON CHEST WALL TISSUES

Radiation therapy induces tissue injury that can be categorized as acute or chronic.18 The spectrum of acute injury includes erythema, edema, desquamation, hyperpigmentation, and ulceration,19 ranging from mild to severe. Acute radiation dermatitis occurs in upward of 85% of treated patients.19,20 Chronic injury involves skin atrophy, dryness, telangiectasia, dyspigmentation, and dyschromia.21 In the breast, it leads to chronic fibrosis of the skin and subcutaneous tissues. This fibrosis and surrounding injury can lead to pain and restricted movement of the arm. The chronic changes from radiation can take months to years to fully manifest.20,22

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TIMING OF RECONSTRUCTION AND RADIATION

Patients generally present at 2 time points as it relates to radiation. They have either been previously radiated or have a high likelihood of requiring PMRT. While both involve radiated fields, the decision points are very different and require a specific discussion in the preoperative, informed consent process.

Breast radiation protocols and dosing can vary greatly by institution, and differences in radiation timing even exist within standard institutional protocols depending on the nature of the cancer and neoadjuvant therapy that has been initiated.23 Radiation oncology continues to evolve with trials and utilization of more directed radiation delivery instead of simply whole breast radiation.24 In an effort to streamline reconstruction in the setting of PMRT, many institutions follow an algorithmic approach.20,25,26 The general protocol for radiation following prosthetic reconstruction at Memorial Sloan Kettering has been recently outlined.27

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PREVIOUS RADIATION THERAPY

Patients who have had previous radiation and present for reconstruction generally fit into 2 main categories. They (1) failed BCT requiring salvage mastectomy and desiring IBR or (2) are true delayed reconstruction following mastectomy and PMRT.

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Tissue Expander/Implant Reconstruction

Patients who have undergone previous radiation traditionally have been discouraged from implant-only breast reconstruction, given a poor complication profile. This setting conveys some of the highest reported rates of reconstructive failure in patients with prosthetic reconstruction but with significant variations and conflicting results existing in the literature. However, recent studies demonstrate that implant reconstruction is more popular in this scenario than autologous modalities.17

Lee and Mun28 in 2015 published a systematic review to better understand the outcomes following prosthetic reconstruction in this patient population. They examined 20 studies all but one of which were retrospective cohort designs. Pooling the analysis, the authors demonstrated an increase in nearly all complications examined. A significantly higher risk of reconstructive failure [14% rate overall; relative risk, 2.58 (1.86–3.57)] and total complications [36% rate overall; relative risk, 1.89 (1.57–2.28)] was noted in radiated patients. Capsular contracture risk was also higher [relative risk, 3.32 (1.36–8.13)], as was risk for infection, mastectomy flap necrosis, and seroma formation. Subgroup analyses were performed in nipple-sparing mastectomies and in the application of ADM to the reconstructions, with similar findings of increased complications.

Additional recent studies continue to cast a concerning shadow on this modality in the setting of prior radiation. In 2016, Chen et al.29 published a retrospective cohort study comparing prosthetic-based reconstruction in patients with preradiation, PMRT, and no radiation. They found an increased risk of complications in the preradiation cohort, with reconstructive failure occurring in 50% of breasts. As such, the authors advocate for autologous reconstruction in this setting. Kearney et al.30 also published a study examining these 3 cohorts but found fewer overall differences in complications. They did, however, note a significant increase in conversion from prosthetic to autologous reconstruction in the preradiation cohort compared with patients without radiation (10.5% versus 0.6%; P = 0.03).30 Reish et al.31 similarly compared these cohorts and also demonstrated higher rates of complications in preradiation and higher rates of explantation in patients with PMRT. Secondary procedures were also higher in the radiated cohort.

SUMMARY POINT: Previous radiation introduces significant risk for implant reconstructive failure and complications though incidence varies widely across institutions. Pooled analysis suggests the incidence of reconstructive failure to be 14%.

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Autologous and Tissue Expander/Implant Reconstruction

Traditional teaching encouraged the use of autologous tissue in conjunction with a prosthetic device in previously radiated fields, which most commonly employs the latissimus dorsi (LD) myocutaneous flap. This allows for the recruitment of healthy tissue to the breast, which covers the device and expands to a better degree than the irradiated surrounding tissues following salvage mastectomy (Fig. 1) or in delayed reconstruction cases following completion of radiation.

Fig. 1.

Fig. 1.

Fischer et al.32 published in 2016 a systematic review on the use of prosthetic breast reconstruction with and without autologous tissue in the radiated field. Pooled results from 31 studies demonstrated a significant decrease in implant loss in the LD/implant group compared with implant-only (15% versus 5%; P < 0.001). Furthermore, odds of loss was 4.33 (P = 0.0003) favoring LD-assisted reconstruction. A similar difference was noted for postoperative infections, although no difference was found in capsular contracture incidence.32

As part of their systematic review of prosthetic reconstruction following premastectomy radiation, Lee and Mun28 also analyzed the use of the LD. They noted a 72% decreased risk of reconstructive failure when autologous tissue and a prosthetic device was utilized as compared with prosthetic device alone (relative risk, 0.28; CI, 0.15–0.52). Reconstructive failure for prosthetic device with autologous tissue was 6.9% compared with 33.7% for prosthetic-only reconstruction. Rate of infection and capsular contracture did not differ.

Use of the LD has been utilized for years in this setting at our center and is often the choice of reconstruction when the previously radiated tissues are fibrosed and not pliable and the patient desires implant-based reconstruction or is not a candidate for an autologous only option. In 2008, we published a series of 57 patients demonstrating the safety of this technique in salvage mastectomy, with a very acceptable complication profile.33 Other recent studies demonstrate that using this for IBR in a salvage setting demonstrate comparable complication profiles to use of the LD and prosthesis in a completely delayed fashion after PMRT.34

SUMMARY POINT: Use of autologous tissue (LD) with implant significantly reduces incidence of reconstructive failure in previously radiated fields (72% decreased risk).28

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Autologous Reconstruction

Autologous tissue has long been considered the cornerstone of breast reconstruction in a radiated field. Bringing healthy, distant tissue into a previously radiated site enables a much more supple, aesthetic reconstruction to be achieved. Compared with implant reconstruction in the setting of previous radiation, the risk of reconstructive loss is 92% decreased.28 However, radiation damage still introduces additional challenges to the reconstruction.

Autologous reconstruction in a radiated field requires operating in a fibrosed environment. The microvasculature is impacted in the surrounding tissues, as are the more macroscopic vessels.35 Several studies have directly examined the impact of prereconstruction radiation. In 2016, Fracol et al.36 at the University of Pennsylvania examined outcomes following prior unilateral radiation in bilateral reconstruction. They showed that microvascular arterial complications were significantly more common in the radiated field—but that this did not impact outcomes overall. This was a follow-up study to a similar study by Fosnot et al.37, which examined 1,025 flaps, 226 of which were placed into radiated beds. Again, an increase in intraoperative vascular complications was noted (14.2% versus 7.6%; P = 0.003) without a change in individual outcomes such as fat necrosis, delayed vascular complications, or flap loss.37 Flap loss was noted to be 3.1% in the radiated cohort compared with 1.5% in patients without radiation (P = 0.13). The authors suggest that such microvascular complications were typically technical and involved the need to revise an anastomosis or further dissect the recipient vessels for a more useable target. As such, additional care and a heightened vigilance for issues with anastomoses should be employed in this setting.

In 2016, de Araujo et al.38 also examined outcomes following prior unilateral chest wall radiation in bilateral patients. Radiation increased the odds for breast-related complications (OR, 2.98; P < 0.0001), infection (OR, 2.59; P = 0.027), and major skin loss (OR, 3.47; P = 0.0266). Interestingly, no difference was noted by modality comparing autologous to implant-based reconstructions (P = 0.76). Furthermore, subgroup analysis yielded no difference in extrusion of implants or in flap losses comparing the radiated to nonradiated sides.

SUMMARY POINT: Autologous tissue is the gold standard for reconstruction in previously radiated fields, though intraoperative microvascular vascular complications as well as postoperative minor complications may be more common in this setting.

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POSTMASTECTOMY RADIATION THERAPY

Debate surrounds the timing and method of reconstruction in the setting of PMRT. For prosthetic reconstruction, the discussion relates to radiating the tissue expander or the final implant. For autologous reconstruction, the debate centers on directly radiating the flap or delaying the reconstruction until after radiation. It is important to remember when considering the following discussion that radiation protocols vary greatly from 1 institution to another. The protocols often differ in terms of timing and radiation dose, which can make comparison difficult as radiation has dose-dependent effects.

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Tissue Expander/Implant Reconstruction

Radiation following immediate prosthetic breast reconstruction occurs at 2 general time points—following the placement of the tissue expander (Fig. 2) or following the final exchange for the permanent implant (Fig. 3). Numerous studies have examined this topic, with conflicting results and conclusions.

Fig. 2.

Fig. 2.

Fig. 3.

Fig. 3.

In 2013, Lam et al.39 published a systematic review attempting to determine optimal sequencing for radiation in 2-stage reconstruction. Overall, 12 studies were included (only 1 prospective), which pooled 715 radiated patients and 1,138 nonradiated patients. Radiation increased reconstructive failure (18.6% versus 3.1%; P < 0.00001), and more specifically, failure occurred at higher rates not only when applied to the expander (29.7% versus 5.0%; P < 0.00001) but also when given directly to the implant (7.7% versus 1.5%; P = 0.0003). This review also noted increased risk of severe capsular contracture for both radiation to the tissue expander (TE) (8.9% versus 0.5%; P = 0.01) and also to the permanent implant (7.9% versus 0.2%; P = 0.002), although no difference between timing was noted.

Lee and Mun40 built upon this in 2017, focusing only on the difference between timing of radiation to either the expander or permanent implant. Their analysis included 8 studies and 899 patients. Again, only 1 prospective study was included. Although the pooled risk of failure tended to be higher in the radiation to TE cohort compared with the radiation to permanent implant cohort (16% versus 10%), no statistical difference was noted [relative risk, 1.72 (0.81–3.64)]. However, a significant difference was noted with regard to capsular contracture, with the radiation to TE cohort having lower risk compared with the radiation to implant cohort (relative risk, 0.44; P < 0.001).

El-Sabawi et al.20 also published a review examining evidence-based outcomes and algorithmic approaches to PMRT. Seventeen studies were included, the majority of which were level III evidence. Most studies examined radiation to the TE, with complication rates ranging widely. Reconstructive failures ranged from 4.8% to 40%, and capsular contracture rates ranged from 12.5% to 53.3%. This review further commented on timing of exchange to permanent implant following PMRT, with results demonstrating increased time from radiation having improved outcomes.41,42 Complication rates following radiation to the permanent implant were slightly lower for loss (0–29%), but higher for capsular contracture (46.6–57.8%). Studies directly comparing timings were not pooled in this review but presented as individual study data. Each study demonstrated a decrease in rate of loss of the prosthesis when PMRT was performed postexchange.20 This group also published a review examining PMRT and breast reconstruction overall. PMRT to the permanent implant was again favored compared with PMRT to the expander (loss rate 18.8% versus 14.7%; P = 0.006).43

Cordeiro et al.27 examined the ideal timing of radiation therapy in 2-stage prosthetic reconstruction, a project which was included in both the reviews by El-Sabawi et al.20 and Lee.40 This article detailed a 9-year period at Memorial Sloan Kettering Cancer Center and specifically compared radiation with the expander (n = 94) and radiation to the implant (n = 210). Cordeiro et al.27 found higher rates of loss when radiating the expander (32% versus 16%; P < 0.01), however importantly noted that radiation to the permanent implant resulted in a lower aesthetic result (P < 0.01) and higher rates of capsular contracture (P < 0.01).

In 2016, Santosa et al.44 published results from the Mastectomy Reconstruction Outcomes Consortium (MROC) study in an effort to provide new data to this discussion. Overall, 150 patients with PMRT were included (104 TE, 46 implant). All patients had follow-up for at least 6 months following their last procedure. No significant differences were noted in any complication or outcome. On examination of the data, the rates of complications were slightly lower in general for the implant group, but not significant. It is possible that a difference was not noted secondary to small sample size or short overall follow-up time. However, these are high-quality data that were prospectively obtained.44 These results continue to demonstrate the challenge in this area of study, with many studies with differing results. That being said, these results are consistent with the systematic review from Lee and Mun.40

In 2014, Momoh et al.45 published a systematic review comparing prosthetic reconstruction in prereconstruction radiated fields compared with PMRT. Interestingly and in contrast to what would be anticipated, given the majority of the other studies discussed above, they found no significant differences comparing the 2 reconstructive time points. Reconstructive failure was similar, at 19% for prereconstruction and 20% for postreconstruction radiation.45 Although they conclude that in both groups there are clinically significant failure rates, it is important to note that in both nearly 80% of patients achieved stable reconstruction.

It should be noted that some groups radiate the expander instead of the implant at the request of the radiation oncologists, who at times desire a deflated tissue expander to radiate the internal mammary lymph nodes and better contour the heart and lungs.

SUMMARY POINT: PMRT significantly increase the risk of reconstructive failure, be it to the tissue expander or implant. Meta-analyses and recent prospective studies suggest no significant difference in the timing of radiation (pooled incidence approaches 20%), though many level III studies exist demonstrating contrary findings.

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Autologous Reconstruction

For patients electing autologous reconstruction in the setting of PMRT, the ideal timing of reconstruction is debated. Some surgeons believe that IBR is ideal in all situations, and that it is okay to radiate a free flap (Fig. 4). Others, wish to not radiate a flap, given the resulting fibrosis and contracture that could be induced to the reconstruction. Out of this debate was born the concept of delayed immediate reconstruction,46,47 a technique for patients desiring autologous reconstruction in which case a tissue expander is placed at the time of mastectomy and acts as a space holder until the definitive need for radiation is determined. Should a patient need to undergo radiation, they would be radiated with an expander in place, preserving some of the breast boundaries. If radiation is not needed, autologous reconstruction could then be performed. This would avoid direct radiation to the flap itself. The alternative for surgeons who wish to avoid irradiating the flap would be true delayed reconstruction.

Fig. 4.

Fig. 4.

Several recent systematic reviews have been completed on the use of autologous abdominally based breast reconstruction in the setting of PMRT. Schaverian et al.48 in 2013 examined IBR with PMRT compared with IBR without PMRT and then also examined IBR with PMRT compared with true delayed autologous reconstruction. The pooled results comparing IBR with PMRT to IBR alone (1,247 patients in total) showed an increased odds of fat necrosis with PMRT (OR, 2.82; P = 0.006), but no significant differences in further complications.

Rochlin et al.49 in 2015 performed an updated, more narrow review that included 11 studies and 337 patients. They found an increased odds of fat necrosis when flaps were directly radiated (OR, 3.13; P = 0.005) among 3 studies with radiated control cohorts, with rates of revision surgery, fat necrosis, and contour irregularities ranging between 16% and 35%. Variable results were noted in aesthetic outcomes. No significant differences were noted regarding revisions, contour irregularities, or aesthetic results.

Yet, while these reviews overall demonstrate a potential increase in fat necrosis, a growing body of recent literature continues to advocate for immediate free tissue reconstruction.50–52 Kelley et al.53 in 2014 reviewed 20 articles examining autologous reconstruction with a slightly different focus—they pooled and compared prereconstruction radiation and PMRT following IBR. Interestingly, they found similar rates of complications between the timing of radiation and reconstruction, with no significant differences including an examination of fat necrosis rates. Flap contracture rates were noted to be 27% in patients with PMRT.53 Mirzabeigi et al.50 presented the University of Pennsylvania experience over a 4-year period and demonstrated that while volume loss (28.3% versus 4.4%; P < 0.0001) and fat necrosis (19.6% versus 3.6%; P = 0.002) were higher in the irradiated IBR cohort, rates of revision surgery did not differ. This finding is somewhat surprising and counterintuitive but supported by other in the implant revision literature.54 This could be related to both patient factors (more advanced breast cancer) or surgeon preference (lower likelihood of successful revision in a radiated field). The authors also present data supporting a difference in fat necrosis based upon the type of flap utilized in this setting, favoring the muscle-sparing free transverse rectus abdominis musculocutaneous flap over the deep inferior epigastric perforator. There is conflicting data on this final point, however, in the literature, as Garvey et al.55 in 2014 demonstrated no difference in this setting based on flap type utilized, but continued higher rates of fat necrosis.

In one of the most important recent studies to date on IBR and PMRT, Billig et al.56 presented an examination of patients undergoing PMRT and autologous reconstruction from the MROC study. No significant differences over 2 years were noted in complications (P = 0.54) comparing IBR to delayed reconstruction, although patients with delayed reconstruction had lower prereconstruction Breast-Q scores for satisfaction and Psychosocial and Sexual Well-Being. Most importantly, no difference in postoperative scores were noted comparing timing of autologous reconstruction and radiation. In the setting of reconstruction, this study demonstrates a similar complication and patient-reported outcome measure (PROMs) profile, but given the small sample size should be interpreted with some caution. This study is the first focused attempt in autologous reconstruction and PMRT to assess PROMs.

SUMMARY POINT: Existing data suggest that directly PMRT following immediate autologous reconstruction may increase the odds of fat necrosis but has little impact on complications and rates of revision surgeries.

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PATIENT-REPORTED OUTCOMES

PROMs are an increasingly utilized metric whereby success of a treatment is determined. The data generated from tools such as the Breast-Q effectively put the final judgment of treatment back into the hands of the patient.57 Autologous reconstruction has become the gold standard for long-term overall breast reconstruction patient-reported satisfaction.58 However, radiation significantly decreases patient satisfaction,59 yet is a needed component of the treatment of the disease process. The decision point is typically not whether or not to undergo radiation but instead is in the choice of timing and modality for reconstruction. To date, unfortunately, there is little data to help with this specific decision-making process.

El-Sabawi et al.60 recently performed a comprehensive review examining patient-reported outcomes of breast reconstruction and PMRT. They examined 29 articles and demonstrated that PMRT was associated with poorer outcomes. Yet, they do note that most studies demonstrate acceptable rates of aesthetic outcomes and satisfaction. However, more importantly, this review brings to light the lack of appropriate PROM data to help accurately address this question.

Examining what PROMs were utilized to reach this conclusion, the authors found that the methodology was generally inadequate for comparison. The majority of studies examined included reported aesthetic outcomes, only 33% of which had data that were actually patient-reported. Within the aesthetic measures, multiple scales and tools were utilized. Only 4 studies were included that utilized the validated Breast-Q, the majority of which were out of Memorial Sloan Kettering Cancer Center.27,59,61,62 Unfortunately, all these articles examined prosthetic reconstruction, and only 1 examined a specific decision point—to radiate the expander or the implant. Comparing these timings in just over 300 patients demonstrated no significant differences in scores.

The MROC study has recently helped to add some important data to this discussion point, which was published after the review by El-Sabawi.60 As mentioned above, Billig et al.56 demonstrate no significant difference in Breast-Q scores as they related to timing of PMRT with autologous reconstruction. To date, the MROC study has yet to present PRO data from prosthetic reconstructions, which undergo PMRT. This study begins to move us in the right direction of a multi-institutional prospective examination of breast reconstruction. However, controlling for institutional variance is challenging. It is also not a randomized study, which would certainly be a difficult study design to carry out in this setting. Continued research is certainly warranted in this field, with a focus on PROMs as a main focus.

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CONCLUSIONS

Radiation is an essential component to breast cancer treatment but often has a detrimental effect on the reconstructive result. Patients who undergo radiation prior to reconstruction experience high rates of prosthetic device loss but can have low rates of autologous flap loss yet higher rates of intraoperative microvascular issues. Furthermore, PMRT can also lead to prosthetic device loss, capsular contracture, and higher rates of infection. In autologous reconstructions, higher rates of fat necrosis and contour deformities are noted, but without changes in revision rates. To date, PROMs are lower in radiated patients, but few differences have been elucidated between or within reconstructive modalities. Research in PROs is needed to better assess the optimal reconstructive modality in the setting of any form of radiation therapy.

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