- Email: [email protected]
Evaluation of mastectomy with immediate autologous latissimus dorsi breast reconstruction following neoadjuvant chemotherapy and radiation therapy: A single institution study of 111 cases of invasive breast carcinoma
Available online at www.sciencedirect.com
ScienceDirect EJSO xx (2016) 1e7
www.ejso.com
Evaluation of mastectomy with immediate autologous latissimus dorsi breast reconstruction following neoadjuvant chemotherapy and radiation therapy: A single institution study of 111 cases of invasive breast carcinoma N. Paillocher a, A.S. Florczak b,*, M. Richard a, J.M. Classe a, A.S. Oger a, P. Raro a, R. Wernert a, G. Lorimier a a
Surgical Oncology Department, West Institute of Cancerology, Centre Paul Papin, Angers, Francec b Plastic Reconstructive Surgery, CHU Angers, Franced Accepted 22 March 2016 Available online - - -
Abstract Purpose: The aim of the study was to evaluate morbidity and patient satisfaction following surgically treated skin-sparing mastectomy (SSM) with immediate breast reconstruction (IBR) following mastectomy with neoadjuvant chemotherapy (NACT), and preoperative radiotherapy (RT), for operable invasive breast cancer. Patients and methods: This retrospective single-institution study included 111 patients who underwent a mastectomy with IBR after RT and/ or NACT for invasive breast carcinoma at the Institut de Cancerologie de l’Ouest Paul Papin from January 1997 to January 2012. Only patients with breast reconstruction by autologous latissimus dorsi flap with (LDI) or without (ALD) implant were considered. The primary endpoints were the delay in therapeutic sequence, post-operative complication rate, surgical revision rate, time of hospitalization and the anonymous analysis of the patient satisfaction survey. Results: 111 patients underwent mastectomy after RT. The median age was 48 years old and the median body mass index (BMI) was 23.6. SSM were performed in 94.5% of cases. The median interval between the end of chemotherapy (CT) and the beginning of RT was 30 days while the median interval between the end of RT and surgery was 41 days. The rate of primary complications was 66.6% including seroma secretion (reduced to 10.8% when seroma secretion was excluded). The necrosis rate was 5.4%. The average patient satisfaction score for the reconstruction was 17 out of 20. Five-year disease-free and overall survival rates were 93.2% and 98.3% respectively with a median follow-up of 31.6 months. There was only one case of local relapse diagnosed after seven years of follow-up. Conclusion: This study shows that our therapeutic sequence does not appear to increase IBR morbidity and remains within the acceptable safety margins of oncological treatment. It also gives a high quality aesthetic result that helps to maintain patient self-esteem. Ó 2016 Elsevier Ltd. All rights reserved.
Keywords: Breast cancer; Skin-sparing mastectomy; Immediate breast reconstruction; Latissimus dorsi flap; Complications; Local recurrence; Satisfaction
Introduction
* Corresponding author. E-mail addresses: [email protected] (N. Paillocher), [email protected] (A.S. Florczak). c www.centrepaulpapin.fr. d www.chu-angers.fr.
Over the last twenty years, numerous oncological surgical techniques have been developed, with IBR reducing the number of surgical procedures. Studies showed that IBR does not interrupt medical follow-up for patients with breast cancer.1,2 Moreover, IBR does not interfere with the early diagnosis of recurrence and does not compromise their treatment.3 No
http://dx.doi.org/10.1016/j.ejso.2016.03.024 0748-7983/Ó 2016 Elsevier Ltd. All rights reserved. Please cite this article in press as: Paillocher N, et al., Evaluation of mastectomy with immediate autologous latissimus dorsi breast reconstruction following neoadjuvant chemotherapy and radiation therapy: A single institution study of 111 cases of invasive breast carcinoma, Eur J Surg Oncol (2016), http://dx.doi.org/10.1016/j.ejso.2016.03.024
2
N. Paillocher et al. / EJSO xx (2016) 1e7
significant difference, in term of survival rates, was found between patients who benefited from IBR and patients who were treated by delayed breast reconstruction (DBR).1,4,5 Therefore, a delay in treatment between surgery and reconstruction is no longer necessary.6 It has been agreed that IBR is beneficial with regard to overall patient care and is an integral part of treatment.7,8 Consequently, it should be possible to offer IBR to every patient. However, a delay in inducing adjuvant treatment such as (CT) or RT could be associated with an increased risk of metastatic scattering and locoregional relapse. The French National Authority for Health (HAS) recommends that RT should start within eight weeks of surgery and within thirty days of surgery for CT.9 Some clinical studies1,10 showed that patients with IBR treatment experienced a 15-day delay on average in introducing CT compared to patients without IBR treatment. This delay is directly related to the post-operative complications of IBR. Furthermore, when postoperative RT is required, most centres discourage IBR due to the deleterious impact of irradiation on long term aesthetic outcomes. For all these reasons, IBR is mostly chosen to be performed after all of the adjuvant treatments have been completed. A preliminary retrospective study was conducted in this same institute from 1997 to 2008, and included 59 patients. Outcomes showed that performing IBR after CT and/or RT did not decrease patient rates in term of the five-year disease-free period and overall survival rates. Moreover, there were no increased rates of recurrence in the group. In the light of these outcomes, the purpose of the current study was to evaluate the morbidity of the reversed protocol: SSM with IBR after NACT and RT. The secondary objectives were to assess patient satisfaction, overall survival rate and disease-free survival. Patients and methods The retrospective study included 111 patients of the Surgical Oncology Department of the Institut de Cancerologie de l’Ouest Paul Papin, Angers, France, from January 1997 to January 2012. Every patient who underwent RT a few weeks prior to receiving surgery for invasive breast cancer with IBR by ALD or LDI was enrolled in the study. Based on the study design, the decision to administer RT treatment was taken in accordance with current guidelines regarding radiologic tumour diameter, the presence of a multicentric disease, lymphovascular invasion, and axillary node status. For each patient benefiting from RT, the treatment was designed to be administered as pre-operative radiotherapy comprising 50 grays in 25 sessions without boosts. CT was based on current guidelines regarding patient age, the radiologic tumour diameter, SBR grading, positivity of the oestrogen receptor, HER2 overexpression, and axillary node status. Initially, six cycles of FEC 100 (5fluorouracile, epirubicin and cyclophosphamide) were administrated followed by three cycles of FEC and three
cycles of taxotere. Herceptin was added when the patient was HER2þ. Indications for SSM were the failure of a conservative treatment, when the ratio of tumour size to breast volume was too great, the presence of multicentric disease, or an invasive tumour associated with extensive ductal carcinoma in situ (DCIS). To preserve breast skin as much as possible, SSM was performed with a peri areola incision. According to the department protocol, axillary nodes were removed by performing a complete lymphadenectomy when the size of the tumour was greater than five centimetres, or when the patient had a multicentric disease and/or nodes were presents. Patient with local relapses, a medical history of breast RT, or no RT indication were excluded from the study. The lack of CT was not considered a patient enrolment restriction. CT was either neoadjuvant or adjuvant depending on whether or not the lumpectomy resection was complete with an appropriately sized margin. Each case was presented and approved at the multidisciplinary oncological staff meeting. The therapeutic sequence was planned prior to treatment. Six different surgeons performed the reconstructions: four oncologists surgeons and two fellows in oncology surgery. Study protocol Patient characteristics (age, BMI, BRCA mutation), tumour characteristics (localization, histology, TNM stage, grade, hormonal status) and treatments (preoperative and surgical treatment as well as reconstructions) were recorded. Post-operative care was analysed in terms of days of hospitalization, existence of primary complications (defined by researchers as a complication occurring within the first month of surgery) and/or secondary complications (defined as complications occurring after the first month of post-operative surgery). The seroma was drained every four days. The drainage system was removed on detecting less than 20 mL when seroma was measuring less than 20 mL of seroma during check. The period of drainage was recorded. The first post-operative consultation was thirty days after surgery. Patient follow-up was every three months during the first year, then every six months during for the next five years. Post-operative consultations were carried out by surgeons in order to assess any late complications (defined as a secondary complication occurring within one month of post-operative surgery). Further procedures such as reconstruction of the nippleeareola complex, breast symmetry or aesthetic improvement (lipofilling, excision of excess skin, etc.) were also recorded. All types of recurrence (local, contralateral, metastatic), the disease-free survival rate, overall survival rates, and median patient follow-up were analysed and evaluated. Each patient included in the study had to complete a satisfaction questionnaire, which was different from the Breast Q, (Table 5). This questionnaire was sent in January
Please cite this article in press as: Paillocher N, et al., Evaluation of mastectomy with immediate autologous latissimus dorsi breast reconstruction following neoadjuvant chemotherapy and radiation therapy: A single institution study of 111 cases of invasive breast carcinoma, Eur J Surg Oncol (2016), http://dx.doi.org/10.1016/j.ejso.2016.03.024
N. Paillocher et al. / EJSO xx (2016) 1e7
2013 and had to be returned by 30th of April 2013. The aim was to increase understanding of the therapeutic sequence from the patient’s perspective. The primary endpoints were the delay in the therapeutic sequence, post-operative complication rate, surgical revision rate, the length of time spent in hospital (in days) and the anonymous patient satisfaction survey. The secondary endpoint was to search for any correlation between patient characteristics, tumour characteristics, type of treatment, duration of hospitalization and the occurrence of primary and/or secondary complications. Statistical analysis The statistical analysis was performed using Chisquared tests. Fisher’s exact test was used when the Chi squared test was not feasible. The median comparisons between groups were calculated with the Wilcoxon test when two groups were compared to each other and with the KruskaleWallis test when more than two groups were analysed. The Kaplan-Meir method was used to compute the survival analysis. Comparisons were made with the log-rank test. Statistical analysis was performed with SAS software. All variable quantitatives are presented using medians and ranges [minimum;maximum]. Univariate logistic regression was performed to determine for prognostic factors of primary complications. Results The patient characteristics, tumour characteristics and surgical pre-operative treatments are presented in detail in Tables 1 and 2. All patients enrolled in the study received RT treatment and underwent a mastectomy. The median interval between the end of CT and the beginning of RT was 30 days [1;330]; the median interval between the end of RT and surgery was 41 days [11;512]. The median hospital stay was 8 days [0;13]. The breast was the only irradiated zone for 22.5% of the study population (n ¼ 25). Mammary irradiation was associated with irradiation of the internal mammary nodes in 2.7% of cases (n ¼ 3), with irradiation of supraclavicular and infraclavicular nodes in 42.3% of cases (n ¼ 47), and with both irradiation of the supraclavicular, infraclavicular and internal mammary nodes in 32.5% of cases (n ¼ 36). RT-related complications such as radiodermatitis were observed in 92% of patients (n ¼ 102). Type of surgical treatment for mastectomy and IBR (Table 2) About ninety five percent (94.6%, n ¼ 105) of the mastectomies were SSM. IBR used the ALD method in 54% (n ¼ 60) of the reconstructions and the LDI technique in 46% of cases (n ¼ 51). A residual tumour was detected on mastectomy in 52.2% of the study population
3
Table 1 Patients and tumour characteristics prior to treatment. Total, N ¼ 111 (%) Median Age (in years) Median BMI Median follow-up (months) T stage T0 T1 T2 T3 T4 N stage N0 N1 N2 M stage M0 M1 after surgery Histological type IDC ILC IDC þ DCIS Others IDC þ ILC SBR Grading I II III Receptor status REþ Receptor status RPþ Cerb2 statusþ
48 [26;66] 23.6 [16.2;35] 31.6 [0;41.42] 1 (0.9%) 25 (22.7%) 61 (55.5%) 21 (19.1%) 2 (1.8%) 45 (40.5%) 60 (54%) 6 (5.5%) 109 (98.2%) 2 (1.8%) 82 (73.9%) 29 (26.1%) 42 (37.8%) 1 (0.9%) 5 (4.5%) 8 (7.3%) 62 (56.4%) 40 (36.3%) 100 (90.1%) 77 (69.4%) 22 (18.8%)
IDC ¼ invasive ductal carcinoma; ILC ¼ invasive lobular carcinoma; DCIS ¼ ductal carcinoma on situ.
(n ¼ 58). No technical difficulties were reported and no further dermatological treatment was necessary. Post-operative follow-up (Table 3) Primary complications were reported in 66.6% (n ¼ 74) of the study population, including seroma. Excluding seroma, the complications rate was down to 10.8% (n ¼ 12). There were no association between tumour characteristics and treatment type (type of CT, irradiated zones, choice of ALD or LDI) to explain the presence of primary complications. The median delay was 36 days [11;161] for the group with no complications and 45 days [17;512] for the group with primary complications. There was a significant correlation (p [ 0.0075) between the time of the RT and surgery: if surgery was performed 7 weeks after completing RT, the rate of complications increased. Univariate logistic regression did not highlight the importance of the link. There was a significant correlation (p ¼ 0.0712) between BMI and the presence of primary complications. Univariate logistic regression highlighted the increasing risk factor of developing a primary complication as the BMI increased. During the study, outcomes showed that 43.2% of the population (n ¼ 48) developed secondary
Please cite this article in press as: Paillocher N, et al., Evaluation of mastectomy with immediate autologous latissimus dorsi breast reconstruction following neoadjuvant chemotherapy and radiation therapy: A single institution study of 111 cases of invasive breast carcinoma, Eur J Surg Oncol (2016), http://dx.doi.org/10.1016/j.ejso.2016.03.024
4
N. Paillocher et al. / EJSO xx (2016) 1e7
Table 2 Surgical treatment.
Table 3 Post-operative follow-up. Total, N ¼ 111 (%)
Skin sparing mastectomy Type of IBR LDI ALD Symmetrisation of the contra-lateral breast At the same time as IBR Delayed Type of surgical symmetrisation Mastopexy Breast reduction Implant Reconstruction of the nipple areola complex
105 (94.6%) 51 (46%) 60 (54%) 43 (38.7%) 5 (4.5%) 38 (34.2%) 3 (2.7%) 34 (30.63%) 6 (5.4%) 55 (49.5%)
complications. A major secondary complication, defined as a limitation of up to 45 of scapulo-humeral joint abduction, or as neurological pain, were found 23.4% (n [ 26) and 9% of the patients (n [ 10) respectively. Minor secondary complications were described as implant hernias, capsular contracture and painful dorsal scar adherence. No significant variable was found to explain the occurrence of secondary complications. Nine additional surgical procedures had to be performed in order to treat primary or secondary complications. However no breast implants had to be removed due to infection. Thirty-five corrective reconstruction procedures were necessary: thirteen prosthetic changes, eleven lipofillings, five additional implants, three flap slidings, one section of the latissimus dorsi muscle nerve, one creation of the sub-mammary fold, and one revision for excess skin.
Total Median hospital stay (in days) Primary complications (<1 month) Seroma Necrosis (skin, muscular flap) Haematoma Infection Secondary complications (>1month) Shoulder adhesive capsulitis Neurogenic pain Dorsal adherence pain Capsular contracture Fat necrosis Displacement of prosthesis Scar disunity Surgical revision Reconstruction revisions Adipocyte graft (lipofilling) Change of breast prosthesis Flap repositioning Add of prosthesis Resection of excess skin Sectioning of the Latissimus dorsi nerve Creation of the sub-mammary fold
8 [0;13] 74 (66.6%) 60 (54%) 6 (5.4%) 4 (3.6%) 2 (1.8%) 48 (43.2%) 26 (23.4%) 12 (9%) 3 (2.7%) 3 (2.7%) 2 (1.8%) 1 (0.9%) 1 (0.9%) 9 (8.1%) 35 (31.5%) 11 (9.9%) 13 (11.7%) 3 (2.7%) 5 (4.5%) 1 (0.9%) 1 (0.9%) 1 (0.9%)
main disadvantages identified were pain, shape asymmetry and reconstructed breast volume. Secondary surgery for symmetrisation was performed for 38.7% of the population (n ¼ 43). Sexuality support was given to 60.8% of the patients who benefited from IBR. Thanks to this support, 90% of the patients declared that they had a more positive view of their body and 93.2% had a higher acceptance of their mastectomy.
Carcinologic follow-up (Table 4) Discussion With a median follow-up of 31.6 months [0;41.42], outcomes showed disease-free survival of 93.2% and an overall survival rate of 98.3% for the study population at five years. There was one case of local recurrence after seven years of follow-up. This was the subcutaneous recurrence of 12 mm invasive ductal carcinoma which was treated by three cycles of CT (Paclitaxel and Capecitabine) and which obtained a clinically and radiologically defined remission. As a simple lumpectomy was performed after the three sessions of CT directly followed by another consolidation of three additional courses, the reconstruction did not have to be removed. Within seven months of the relapse, the patient was in complete remission. Nine cases of metastatic relapse were described, occasionally with mixed localizations. One patient died from cerebral metastases. Seventy-four patients (67.3%) answered the satisfaction questionnaire. The mean grade of satisfaction was 17 out of 20 (Table 5), which is considered a high patient satisfaction score. Seventy percent of the population (n ¼ 52) stated that they would choose the exact same treatment again if necessary. Approximately 30% of the population (n ¼ 22) who answered the questionnaire raised no criticism. The
In the literature, we found very few studies on this subject.11e13 The first trial conducted at the Jean Perrin Comprehensive Cancer Centre monitoring 210 patients11 showed no effect on long-term survival rates. Morbidity In our study, no predictive risk factors of surgical complications were found to be significant. However, Table 4 Relapse and survival. Total Median follow-up Relapse Nature of relapse Local Metastatic Five-year disease-free survival Overall survival at five years Death
31.6 months [0;41.42] 10 (9%) 1 (0.9%) 9 (8.1%) 93.2% [83.4%; 97.2%] 98.3% [88.9%; 99.7%] 1 (0.9%)
Please cite this article in press as: Paillocher N, et al., Evaluation of mastectomy with immediate autologous latissimus dorsi breast reconstruction following neoadjuvant chemotherapy and radiation therapy: A single institution study of 111 cases of invasive breast carcinoma, Eur J Surg Oncol (2016), http://dx.doi.org/10.1016/j.ejso.2016.03.024
N. Paillocher et al. / EJSO xx (2016) 1e7
5
Surgical complications
Table 5 Satisfaction survey. Total N ¼ 74 Survey participation rate 67.3% Average satisfaction score 17/20 Do you have any criticisms concerning IBR: No 22 (29.7%) Yes 33 (44.6%) Please specify: (multiple-choice questions) Painful 10 (13.5%) Problem of symmetry 7 (9.5%) Volume problem 5 (6.7%) Problem of nipple areola complex 4 (5.4%) Problem of shape 3 (4%) Prominent axilla protuberance 1 (1.3%) Muscle contraction of flap 1 (1.3%) Necrosis 1 (1.3%) Poor clinical course over several years 1 (1.3%) Do you have back problems? No 32 (51.6%) Please specify: (multiple-choice questions) Dorsal pain 10 (16.1%) Aesthetically unpleasant scars 2 (3.2%) Adhesion 16 (25.8%) Seroma requiring draining 2 (3.2%) Would you like to undergo another procedure to improve the cosmetic result? Yes 16 (21.9%) No 57 (78%) Has the nippleeareola complex been reconstructed? Yes 41 (66.2%) - Satisfied 38 (92.7%) - Dissatisfied 3 (7.3%) No 33 (45.2%) - No required 26 (78.8%) Symmetrisation of contralateral breast? Yes 29 (40.3%) - Satisfied 26 (89.6%) - Dissatisfied 1 (3.4%) - No response 2 (6.89%) No 45 (59.7%) Would you do anything differently? No, i would have the same treatment 52 (70.3%) IBR but with a different technique 22 (29.7%) Wait a few monts after the mastectomy before DBR 1 (1.35%) No reconstruction 1 (1.35%) Adequate information supplied 70 (94.6%) Adequate reflection period 70 (94.6%) Have you been given support to accept the loss of your breast? Yes 69 (93.2%) No 3 (4%) No response 2 (2.7%) Have you been given support to accept your new body? Yes 66 (90%) No 5 (6.8%) No answer 2 (2.7%) Have you received sexuality support? Yes 45 (60.8%) No 16 (21.6%) Don’t know or no response 12 (16.2%)
according to the literature, smoking, obesity, diabetes and cardiovascular events are predictive factors associated with a lower capacity of healing and poorer aesthetic results.14,15
In this study, primary complications (excluding seroma) affected 10.8% of the patients. This concurred with the published date since Michy et al.11 reported a similar rate of 17.1% for primary complications. However, the production of seroma on donor site (former location of latissimus dorsi) was high (54%) whereas rates of 4.8% and 15.3% were reported by Monrigal et al.13 and Giacalone et al.16 respectively. The incidence of complications due to seroma production was previously reported to be high in approximately 80% of patients.17 In our study, preventive measures (such as fibrin sealants or Chippendale’s technique18) were not utilized. Our technique was described as an ALD flap (die-cut of the fascia superficialis), which could explain our high rate of seroma. Compared to the literature, our series showed a lower rate of necrosis (breast skin or donor site) (5.4%) than the studies of Giacalone et al.16 or Monrigal et al.13 who found 30.7% and 10% of dorsal necrosis or excess skin respectively. These outcomes lead us to presume that several surgical techniques may account for such differences in terms of necrotic complications. Our surgical procedure involved de-epidermisation of the latissimus dorsi flap.19 Our low rate of necrosis could be due to using the muscular flap, which could be helpful in the skin healing and nourishing process, by improving trophicity following RT treatment. Indeed, we believe that surgery performed between four to eight weeks after RT decreased the rate of flap and breast skin necrosis due to the acute local inflammatory response that enhanced blood flow as shown in the Hu et al. study.20 In this study,20 cutaneous blood flow through the irradiated breast, increased from 13.83 (5.01) perfusion units to 68.73 (57.70) perfusion units at the end of radiotherapy. It is now well documented that for many irradiated breast reconstructions, autologous reconstructions are the best choice in terms of aesthetic outcomes and risk management.21 In our study, cases of IBR for ipsilateral recurrence after lumpectomy and previous radiation were excluded in order to consider only recent pre-operative RT which ended a few weeks before surgery. We could therefore estimate the immediate, not long-term, side effects of RT on healing. As regards the IBR techniques, each one has its own indications. In the case of the radiation dose before surgery, we opted for the strategy that uses a latissimus dorsi (LD) flap for IBR but we did not contraindicate other techniques. The choice of surgery still has to meet the medical standards of oncological treatment, the patient’s physical condition and morphology and the patient’s wishes. However, as a mastectomy is known to be a traumatic event in a woman’s life, none of these factors should be considered as a contraindication for IBR. Nevertheless, information on morbidity, complication rates, and the impact of surgery on routine daily activities must be given to patients to
Please cite this article in press as: Paillocher N, et al., Evaluation of mastectomy with immediate autologous latissimus dorsi breast reconstruction following neoadjuvant chemotherapy and radiation therapy: A single institution study of 111 cases of invasive breast carcinoma, Eur J Surg Oncol (2016), http://dx.doi.org/10.1016/j.ejso.2016.03.024
6
N. Paillocher et al. / EJSO xx (2016) 1e7
enable them to decide whether or not they wish to undergo this type of surgical procedure. There are no significant differences between ALD and LDI in terms of early and delayed complications and surgical revision. The Monrigal et al. study13 showed that transverse rectus abdominis musculo-cutaneous (TRAM) flap and retropectoral implant (RI) reconstructions required more surgical revisions than LD reconstructions (RR TRAM vs LD ¼ 2.7 [1.4e5.3] and RR RI vs LD ¼ 4.2 [2.0e8.6], p ¼ 0.0006). Furthermore, Berry et al.22 found that radiation did not significantly impact upon complication rates (p ¼ 0.51 for total complications and p ¼ 0.79 for major complications) and showed that autologous tissue may be the best choice for reconstruction after RT (lower major complication rates compared to implant reconstruction). Our rate of capsular contracture was 2.7% which is considered low. The meta-analysis by Barry et al.23 demonstrated that autologous reconstruction is the best technique in terms of post-operative morbidity including capsular contracture. Furthermore, we think that placing the LD flap between the prostheses and skin that has undergone RT decreases the rate of capsular contractures. Patient satisfaction Patients who had IBR experienced less distress and better psychosocial well-being than those who had DBR.24,25 In the Giacalone et al. study,16 89% of patients were satisfied with the aesthetic result. This study compared two cohorts: one with 26 patients treated by CT, RT and then SSM and IBR with LDI and another with 78 patients undergoing a mastectomy followed by CT, RT and DBR. There was no significant difference between the two groups. A metaanalysis performed by Barry et al.23 confirmed the high patient satisfaction rate (natural appearance, psychosocial benefits, quality of life). The key to high quality patient care lies in the ability to respond to our patients’ needs and consistently frequent monitoring by the same medical care providers. The high patient satisfaction rate could be attributed to the reflection period prior to surgery, in addition to the surgical procedure (mastectomy and IBR), numerous consultations with the surgeon and the information given. This reflection period gave patients time to grieve for the loss of their breast. However, some patients criticized their IBR due to an unsatisfactory aesthetic outcome or dorsal after-effects. Therefore it appears essential to inform patients of the potential risk of complications (loss of sensitivity in the reconstructed breast,26 back pain, etc.) and how to manage them (importance of physiotherapy preventing poor posture and scar tissue adhesions). Patients need to be prepared by the surgeon for the aesthetic outcome (approximate symmetry, frequent need for surgical revision). The survey should remain anonymous to allow each patient to voice criticisms or express her wishes about medical care. The results of our satisfaction questionnaire
showed several expressions of gratitude and high satisfaction rates in terms of the cosmetic result. The high survey participation rate showed that patients were looking forward to sharing their opinions on the personal aspects of benefitting from an IBR. Obviously, the results could be improved by adding an approved questionnaire such as the BREAST e Q test but as this was a retrospective study over 10 years, we chose a simpler questionnaire in order to obtain the maximum number of responses. Oncological follow-up Our aim objective was to estimate the disease-free period and overall survival rates in patients who underwent this therapeutic sequence. With a median follow-up of 31.6 months, we noticed only one local recurrence of ductal carcinoma after seven years of follow-up for a lobular carcinoma treated by IBR without SSM. In terms of the overall survival rate, the literature highlighted a survival rate of 75% in the Michy et al. study11. In our study, the five year overall survival rate was higher (93.2%). Giacalone et al.16 reported a local recurrence rate of 7.7% after a median follow-up of 4.1 years for stage two and stage three patients who benefitted from pre-operative CT and RT prior to reconstruction by SSM and LDI. Monrigal et al.13 did not report any significant difference in terms of local recurrence and regional nodal recurrence, which leads us to believe that this strategy does not alter locoregional tumour control. Conclusion This phase II study assesses the feasibility and morbidity of SSM and IBR with an LD flap after NACT and RT in invasive breast carcinoma (M-RIC). To confirm our observations, other studies should be carried out, such as prospective studies comparing two groups (pre- and postoperative radiation and reconstruction) to evaluate the superiority of one of the therapeutic sequences. We are looking forward to the conclusion of the French multicentric clinical trial (M-RIC), in which our department participated in 2012. The results of this trial should be published shortly. Conflicts of interest statement None.
References 1. Newman LA, Kuerer HM, Hunet KK, et al. Presentation, treatment, and outcome of local recurrence after skin-sparing mastectomy and immediate breast reconstruction. Ann Surg Oncol 1998;5:620–6. 2. Howard MA, Polo K, Pusic AL, et al. Breast cancer local recurrence after mastectomy and TRAM flap reconstruction: incidence and treatment options. Plast Reconstr Surg 2006;117:1381–6.
Please cite this article in press as: Paillocher N, et al., Evaluation of mastectomy with immediate autologous latissimus dorsi breast reconstruction following neoadjuvant chemotherapy and radiation therapy: A single institution study of 111 cases of invasive breast carcinoma, Eur J Surg Oncol (2016), http://dx.doi.org/10.1016/j.ejso.2016.03.024
N. Paillocher et al. / EJSO xx (2016) 1e7 3. Garbay JR, Saouma S, Marsiglia H. Progress in immediate breast reconstruction with skin sparing mastectomy. Ann Chir Plast Esthet 2008;53:199–207. 4. Slavin SA, Love SM, Goldwyn RM. Recurrent breast cancer following immediate reconstruction with myocutaneous flaps. Plast Reconstr Surg 1994;93:1191–207. 5. Kroll SS, Khoo A, Singletary SE, et al. Local recurrence risk after skin-sparing and conventional mastectomy: a 6-year follow-up. Plast Reconstr Surg 1999;104(2):421–5. 6. McKeown DJ, Hogg FJ, Brown MJ, et al. The timing of autologous latissimus dorsi breast reconstruction and effect of radiotherapy on outcome. Plast Reconstr Surg 2009;62:488–93. 7. Gouy S, Rouzier R, Missana, et al. Immediate reconstruction after neoadjuvant chemotherapy: effect on adjuvant treatment starting and survival. Ann Surg Oncol 2005;12(2):161–6. 8. Knottenbelt A, Spauwen PH, Wobbes T. The oncological implications of immediate breast reconstruction. Eur J Surg Oncol 2004;30(8):829– 33. 9. Agence nationale d’accreditation et d’evaluation en sante. Chirurgie des lesions mammaires : prise en charge de premiere intention. Paris: ANAES; 2002. 10. Kontos M, Lewis RS, L€uchtenborg M, et al. Does immediate breast reconstruction using free flaps lead to delay in the administration of adjuvant chemotherapy for breast cancer? Eur J Surg Oncol 2010; 36:745–9. 11. Michy T, Gimbergues P, Le Bou€edec G, et al. What surgical procedure for immediate breast reconstruction after preoperative radiotherapy and chemotherapy? J Chir 2007;144(6):511–5. 12. Taylor CW, Kumar S. The effect of immediate breast reconstruction on adjuvant chemotherapy. Breast 2005;14(1):18–21. 13. Monrigal E, Dauplat J, Gimbergues P, et al. Mastectomy with immediate breast reconstruction after neoadjuvant chemotherapy and radiation therapy. A new option for patients with operable invasive breast cancer. Results of 20 years single institution study. EJSO 2011;(37): 864–70. 14. Chang DW, Reece GP, Wang B, et al. Effect of smoking on complications in patients undergoing free TRAM flap breast reconstruction. Plast Reconstr Surg 2000 Jun;105(7):2374–80. 15. Chang DW, Wang B, Robb GL, et al. Effect of obesity on flap and donor e site complications in free transverse rectus abdominis
16.
17.
18.
19.
20.
21.
22.
23. 24.
25.
26.
7
myocutaneous flap breast reconstruction. Plast Reconstr Surg 2000 Apr;105(5):1640–8. Giacalone PL, Rathat G, Daures JP, et al. New concept for immediate breast reconstruction for invasive cancers: feasibility, oncological safety and esthetic outcome of post-neoadjuvant therapy immediate breast reconstruction versus delayed breast reconstruction: a prospective pilot study. Breast Cancer Res Treat 2010;122:439–51. Lee KT, Mun GH. Fibrin sealants and quilting suture for prevention of seroma formation following latissimus dorsi muscle harvest: a systematic review and meta-analysis. Aesthetic Plast Surg 2015 Jun;39(3): 399–409. Gisquet H, Delay E, Paradol PO, et al. Prevention of seroma by quilting suture after harvesting latissimus dorsi flap. The “Chippendale” technique. Ann Chir Plast Esthet 2010 Apr;55(2):97–103. Delbaere M, Delaporte T, Toussoun G, et al. Skin e sparing mastectomy: how to avoid skin necrosis? Ann Chir Plast Esthet 2008;53: 208–25. Sc Hu, Hou MF, Luo KH, et al. Changes in biophysical properties of the skin following radiotherapy for breast cancer. J Dermatol 2014 Dec;41(12):1087–94. Spear SL, Boehmler JH, Taylor NS, Prada C. The role of the latissimus dorsi flap in reconstruction of the irritatied breast. Plast Reconstr Surg 2007 Jan;119(1):1–9. Berry MD, Brooks MD, Sydow MD, et al. Complications rates of radiation on tissue expander and autologous tissue breast reconstruction. Ann Surg Oncol 2010;17:S202–10. Barry M, Kell MR. Radiotherapy and breast reconstruction: a metaanalysis. Breast Cancer Res Treat 2011;127:15–22. Al-Ghazal SK, Fallowfield L, Blamey RW. The psychological impact of immediate rather than delayed breast reconstruction. Eur J Surg Oncol 2000;26(1):17–9. Reefy S, Patani N, Anderson A, et al. Oncological outcome and patient satisfaction with skin-sparing mastectomy and immediate breast reconstruction: a prospective observation study. BMC Cancer 2010; 10:171. Delay E, Jorquera F, Lucas R, et al. Sensitivity of breasts reconstructed with the autologous latissimus dorsi flap. Plast Reconstr Surg 2000; 106(2):302–9.
Please cite this article in press as: Paillocher N, et al., Evaluation of mastectomy with immediate autologous latissimus dorsi breast reconstruction following neoadjuvant chemotherapy and radiation therapy: A single institution study of 111 cases of invasive breast carcinoma, Eur J Surg Oncol (2016), http://dx.doi.org/10.1016/j.ejso.2016.03.024
ScienceDirect EJSO xx (2016) 1e7
www.ejso.com
Evaluation of mastectomy with immediate autologous latissimus dorsi breast reconstruction following neoadjuvant chemotherapy and radiation therapy: A single institution study of 111 cases of invasive breast carcinoma N. Paillocher a, A.S. Florczak b,*, M. Richard a, J.M. Classe a, A.S. Oger a, P. Raro a, R. Wernert a, G. Lorimier a a
Surgical Oncology Department, West Institute of Cancerology, Centre Paul Papin, Angers, Francec b Plastic Reconstructive Surgery, CHU Angers, Franced Accepted 22 March 2016 Available online - - -
Abstract Purpose: The aim of the study was to evaluate morbidity and patient satisfaction following surgically treated skin-sparing mastectomy (SSM) with immediate breast reconstruction (IBR) following mastectomy with neoadjuvant chemotherapy (NACT), and preoperative radiotherapy (RT), for operable invasive breast cancer. Patients and methods: This retrospective single-institution study included 111 patients who underwent a mastectomy with IBR after RT and/ or NACT for invasive breast carcinoma at the Institut de Cancerologie de l’Ouest Paul Papin from January 1997 to January 2012. Only patients with breast reconstruction by autologous latissimus dorsi flap with (LDI) or without (ALD) implant were considered. The primary endpoints were the delay in therapeutic sequence, post-operative complication rate, surgical revision rate, time of hospitalization and the anonymous analysis of the patient satisfaction survey. Results: 111 patients underwent mastectomy after RT. The median age was 48 years old and the median body mass index (BMI) was 23.6. SSM were performed in 94.5% of cases. The median interval between the end of chemotherapy (CT) and the beginning of RT was 30 days while the median interval between the end of RT and surgery was 41 days. The rate of primary complications was 66.6% including seroma secretion (reduced to 10.8% when seroma secretion was excluded). The necrosis rate was 5.4%. The average patient satisfaction score for the reconstruction was 17 out of 20. Five-year disease-free and overall survival rates were 93.2% and 98.3% respectively with a median follow-up of 31.6 months. There was only one case of local relapse diagnosed after seven years of follow-up. Conclusion: This study shows that our therapeutic sequence does not appear to increase IBR morbidity and remains within the acceptable safety margins of oncological treatment. It also gives a high quality aesthetic result that helps to maintain patient self-esteem. Ó 2016 Elsevier Ltd. All rights reserved.
Keywords: Breast cancer; Skin-sparing mastectomy; Immediate breast reconstruction; Latissimus dorsi flap; Complications; Local recurrence; Satisfaction
Introduction
* Corresponding author. E-mail addresses: [email protected] (N. Paillocher), [email protected] (A.S. Florczak). c www.centrepaulpapin.fr. d www.chu-angers.fr.
Over the last twenty years, numerous oncological surgical techniques have been developed, with IBR reducing the number of surgical procedures. Studies showed that IBR does not interrupt medical follow-up for patients with breast cancer.1,2 Moreover, IBR does not interfere with the early diagnosis of recurrence and does not compromise their treatment.3 No
http://dx.doi.org/10.1016/j.ejso.2016.03.024 0748-7983/Ó 2016 Elsevier Ltd. All rights reserved. Please cite this article in press as: Paillocher N, et al., Evaluation of mastectomy with immediate autologous latissimus dorsi breast reconstruction following neoadjuvant chemotherapy and radiation therapy: A single institution study of 111 cases of invasive breast carcinoma, Eur J Surg Oncol (2016), http://dx.doi.org/10.1016/j.ejso.2016.03.024
2
N. Paillocher et al. / EJSO xx (2016) 1e7
significant difference, in term of survival rates, was found between patients who benefited from IBR and patients who were treated by delayed breast reconstruction (DBR).1,4,5 Therefore, a delay in treatment between surgery and reconstruction is no longer necessary.6 It has been agreed that IBR is beneficial with regard to overall patient care and is an integral part of treatment.7,8 Consequently, it should be possible to offer IBR to every patient. However, a delay in inducing adjuvant treatment such as (CT) or RT could be associated with an increased risk of metastatic scattering and locoregional relapse. The French National Authority for Health (HAS) recommends that RT should start within eight weeks of surgery and within thirty days of surgery for CT.9 Some clinical studies1,10 showed that patients with IBR treatment experienced a 15-day delay on average in introducing CT compared to patients without IBR treatment. This delay is directly related to the post-operative complications of IBR. Furthermore, when postoperative RT is required, most centres discourage IBR due to the deleterious impact of irradiation on long term aesthetic outcomes. For all these reasons, IBR is mostly chosen to be performed after all of the adjuvant treatments have been completed. A preliminary retrospective study was conducted in this same institute from 1997 to 2008, and included 59 patients. Outcomes showed that performing IBR after CT and/or RT did not decrease patient rates in term of the five-year disease-free period and overall survival rates. Moreover, there were no increased rates of recurrence in the group. In the light of these outcomes, the purpose of the current study was to evaluate the morbidity of the reversed protocol: SSM with IBR after NACT and RT. The secondary objectives were to assess patient satisfaction, overall survival rate and disease-free survival. Patients and methods The retrospective study included 111 patients of the Surgical Oncology Department of the Institut de Cancerologie de l’Ouest Paul Papin, Angers, France, from January 1997 to January 2012. Every patient who underwent RT a few weeks prior to receiving surgery for invasive breast cancer with IBR by ALD or LDI was enrolled in the study. Based on the study design, the decision to administer RT treatment was taken in accordance with current guidelines regarding radiologic tumour diameter, the presence of a multicentric disease, lymphovascular invasion, and axillary node status. For each patient benefiting from RT, the treatment was designed to be administered as pre-operative radiotherapy comprising 50 grays in 25 sessions without boosts. CT was based on current guidelines regarding patient age, the radiologic tumour diameter, SBR grading, positivity of the oestrogen receptor, HER2 overexpression, and axillary node status. Initially, six cycles of FEC 100 (5fluorouracile, epirubicin and cyclophosphamide) were administrated followed by three cycles of FEC and three
cycles of taxotere. Herceptin was added when the patient was HER2þ. Indications for SSM were the failure of a conservative treatment, when the ratio of tumour size to breast volume was too great, the presence of multicentric disease, or an invasive tumour associated with extensive ductal carcinoma in situ (DCIS). To preserve breast skin as much as possible, SSM was performed with a peri areola incision. According to the department protocol, axillary nodes were removed by performing a complete lymphadenectomy when the size of the tumour was greater than five centimetres, or when the patient had a multicentric disease and/or nodes were presents. Patient with local relapses, a medical history of breast RT, or no RT indication were excluded from the study. The lack of CT was not considered a patient enrolment restriction. CT was either neoadjuvant or adjuvant depending on whether or not the lumpectomy resection was complete with an appropriately sized margin. Each case was presented and approved at the multidisciplinary oncological staff meeting. The therapeutic sequence was planned prior to treatment. Six different surgeons performed the reconstructions: four oncologists surgeons and two fellows in oncology surgery. Study protocol Patient characteristics (age, BMI, BRCA mutation), tumour characteristics (localization, histology, TNM stage, grade, hormonal status) and treatments (preoperative and surgical treatment as well as reconstructions) were recorded. Post-operative care was analysed in terms of days of hospitalization, existence of primary complications (defined by researchers as a complication occurring within the first month of surgery) and/or secondary complications (defined as complications occurring after the first month of post-operative surgery). The seroma was drained every four days. The drainage system was removed on detecting less than 20 mL when seroma was measuring less than 20 mL of seroma during check. The period of drainage was recorded. The first post-operative consultation was thirty days after surgery. Patient follow-up was every three months during the first year, then every six months during for the next five years. Post-operative consultations were carried out by surgeons in order to assess any late complications (defined as a secondary complication occurring within one month of post-operative surgery). Further procedures such as reconstruction of the nippleeareola complex, breast symmetry or aesthetic improvement (lipofilling, excision of excess skin, etc.) were also recorded. All types of recurrence (local, contralateral, metastatic), the disease-free survival rate, overall survival rates, and median patient follow-up were analysed and evaluated. Each patient included in the study had to complete a satisfaction questionnaire, which was different from the Breast Q, (Table 5). This questionnaire was sent in January
Please cite this article in press as: Paillocher N, et al., Evaluation of mastectomy with immediate autologous latissimus dorsi breast reconstruction following neoadjuvant chemotherapy and radiation therapy: A single institution study of 111 cases of invasive breast carcinoma, Eur J Surg Oncol (2016), http://dx.doi.org/10.1016/j.ejso.2016.03.024
N. Paillocher et al. / EJSO xx (2016) 1e7
2013 and had to be returned by 30th of April 2013. The aim was to increase understanding of the therapeutic sequence from the patient’s perspective. The primary endpoints were the delay in the therapeutic sequence, post-operative complication rate, surgical revision rate, the length of time spent in hospital (in days) and the anonymous patient satisfaction survey. The secondary endpoint was to search for any correlation between patient characteristics, tumour characteristics, type of treatment, duration of hospitalization and the occurrence of primary and/or secondary complications. Statistical analysis The statistical analysis was performed using Chisquared tests. Fisher’s exact test was used when the Chi squared test was not feasible. The median comparisons between groups were calculated with the Wilcoxon test when two groups were compared to each other and with the KruskaleWallis test when more than two groups were analysed. The Kaplan-Meir method was used to compute the survival analysis. Comparisons were made with the log-rank test. Statistical analysis was performed with SAS software. All variable quantitatives are presented using medians and ranges [minimum;maximum]. Univariate logistic regression was performed to determine for prognostic factors of primary complications. Results The patient characteristics, tumour characteristics and surgical pre-operative treatments are presented in detail in Tables 1 and 2. All patients enrolled in the study received RT treatment and underwent a mastectomy. The median interval between the end of CT and the beginning of RT was 30 days [1;330]; the median interval between the end of RT and surgery was 41 days [11;512]. The median hospital stay was 8 days [0;13]. The breast was the only irradiated zone for 22.5% of the study population (n ¼ 25). Mammary irradiation was associated with irradiation of the internal mammary nodes in 2.7% of cases (n ¼ 3), with irradiation of supraclavicular and infraclavicular nodes in 42.3% of cases (n ¼ 47), and with both irradiation of the supraclavicular, infraclavicular and internal mammary nodes in 32.5% of cases (n ¼ 36). RT-related complications such as radiodermatitis were observed in 92% of patients (n ¼ 102). Type of surgical treatment for mastectomy and IBR (Table 2) About ninety five percent (94.6%, n ¼ 105) of the mastectomies were SSM. IBR used the ALD method in 54% (n ¼ 60) of the reconstructions and the LDI technique in 46% of cases (n ¼ 51). A residual tumour was detected on mastectomy in 52.2% of the study population
3
Table 1 Patients and tumour characteristics prior to treatment. Total, N ¼ 111 (%) Median Age (in years) Median BMI Median follow-up (months) T stage T0 T1 T2 T3 T4 N stage N0 N1 N2 M stage M0 M1 after surgery Histological type IDC ILC IDC þ DCIS Others IDC þ ILC SBR Grading I II III Receptor status REþ Receptor status RPþ Cerb2 statusþ
48 [26;66] 23.6 [16.2;35] 31.6 [0;41.42] 1 (0.9%) 25 (22.7%) 61 (55.5%) 21 (19.1%) 2 (1.8%) 45 (40.5%) 60 (54%) 6 (5.5%) 109 (98.2%) 2 (1.8%) 82 (73.9%) 29 (26.1%) 42 (37.8%) 1 (0.9%) 5 (4.5%) 8 (7.3%) 62 (56.4%) 40 (36.3%) 100 (90.1%) 77 (69.4%) 22 (18.8%)
IDC ¼ invasive ductal carcinoma; ILC ¼ invasive lobular carcinoma; DCIS ¼ ductal carcinoma on situ.
(n ¼ 58). No technical difficulties were reported and no further dermatological treatment was necessary. Post-operative follow-up (Table 3) Primary complications were reported in 66.6% (n ¼ 74) of the study population, including seroma. Excluding seroma, the complications rate was down to 10.8% (n ¼ 12). There were no association between tumour characteristics and treatment type (type of CT, irradiated zones, choice of ALD or LDI) to explain the presence of primary complications. The median delay was 36 days [11;161] for the group with no complications and 45 days [17;512] for the group with primary complications. There was a significant correlation (p [ 0.0075) between the time of the RT and surgery: if surgery was performed 7 weeks after completing RT, the rate of complications increased. Univariate logistic regression did not highlight the importance of the link. There was a significant correlation (p ¼ 0.0712) between BMI and the presence of primary complications. Univariate logistic regression highlighted the increasing risk factor of developing a primary complication as the BMI increased. During the study, outcomes showed that 43.2% of the population (n ¼ 48) developed secondary
Please cite this article in press as: Paillocher N, et al., Evaluation of mastectomy with immediate autologous latissimus dorsi breast reconstruction following neoadjuvant chemotherapy and radiation therapy: A single institution study of 111 cases of invasive breast carcinoma, Eur J Surg Oncol (2016), http://dx.doi.org/10.1016/j.ejso.2016.03.024
4
N. Paillocher et al. / EJSO xx (2016) 1e7
Table 2 Surgical treatment.
Table 3 Post-operative follow-up. Total, N ¼ 111 (%)
Skin sparing mastectomy Type of IBR LDI ALD Symmetrisation of the contra-lateral breast At the same time as IBR Delayed Type of surgical symmetrisation Mastopexy Breast reduction Implant Reconstruction of the nipple areola complex
105 (94.6%) 51 (46%) 60 (54%) 43 (38.7%) 5 (4.5%) 38 (34.2%) 3 (2.7%) 34 (30.63%) 6 (5.4%) 55 (49.5%)
complications. A major secondary complication, defined as a limitation of up to 45 of scapulo-humeral joint abduction, or as neurological pain, were found 23.4% (n [ 26) and 9% of the patients (n [ 10) respectively. Minor secondary complications were described as implant hernias, capsular contracture and painful dorsal scar adherence. No significant variable was found to explain the occurrence of secondary complications. Nine additional surgical procedures had to be performed in order to treat primary or secondary complications. However no breast implants had to be removed due to infection. Thirty-five corrective reconstruction procedures were necessary: thirteen prosthetic changes, eleven lipofillings, five additional implants, three flap slidings, one section of the latissimus dorsi muscle nerve, one creation of the sub-mammary fold, and one revision for excess skin.
Total Median hospital stay (in days) Primary complications (<1 month) Seroma Necrosis (skin, muscular flap) Haematoma Infection Secondary complications (>1month) Shoulder adhesive capsulitis Neurogenic pain Dorsal adherence pain Capsular contracture Fat necrosis Displacement of prosthesis Scar disunity Surgical revision Reconstruction revisions Adipocyte graft (lipofilling) Change of breast prosthesis Flap repositioning Add of prosthesis Resection of excess skin Sectioning of the Latissimus dorsi nerve Creation of the sub-mammary fold
8 [0;13] 74 (66.6%) 60 (54%) 6 (5.4%) 4 (3.6%) 2 (1.8%) 48 (43.2%) 26 (23.4%) 12 (9%) 3 (2.7%) 3 (2.7%) 2 (1.8%) 1 (0.9%) 1 (0.9%) 9 (8.1%) 35 (31.5%) 11 (9.9%) 13 (11.7%) 3 (2.7%) 5 (4.5%) 1 (0.9%) 1 (0.9%) 1 (0.9%)
main disadvantages identified were pain, shape asymmetry and reconstructed breast volume. Secondary surgery for symmetrisation was performed for 38.7% of the population (n ¼ 43). Sexuality support was given to 60.8% of the patients who benefited from IBR. Thanks to this support, 90% of the patients declared that they had a more positive view of their body and 93.2% had a higher acceptance of their mastectomy.
Carcinologic follow-up (Table 4) Discussion With a median follow-up of 31.6 months [0;41.42], outcomes showed disease-free survival of 93.2% and an overall survival rate of 98.3% for the study population at five years. There was one case of local recurrence after seven years of follow-up. This was the subcutaneous recurrence of 12 mm invasive ductal carcinoma which was treated by three cycles of CT (Paclitaxel and Capecitabine) and which obtained a clinically and radiologically defined remission. As a simple lumpectomy was performed after the three sessions of CT directly followed by another consolidation of three additional courses, the reconstruction did not have to be removed. Within seven months of the relapse, the patient was in complete remission. Nine cases of metastatic relapse were described, occasionally with mixed localizations. One patient died from cerebral metastases. Seventy-four patients (67.3%) answered the satisfaction questionnaire. The mean grade of satisfaction was 17 out of 20 (Table 5), which is considered a high patient satisfaction score. Seventy percent of the population (n ¼ 52) stated that they would choose the exact same treatment again if necessary. Approximately 30% of the population (n ¼ 22) who answered the questionnaire raised no criticism. The
In the literature, we found very few studies on this subject.11e13 The first trial conducted at the Jean Perrin Comprehensive Cancer Centre monitoring 210 patients11 showed no effect on long-term survival rates. Morbidity In our study, no predictive risk factors of surgical complications were found to be significant. However, Table 4 Relapse and survival. Total Median follow-up Relapse Nature of relapse Local Metastatic Five-year disease-free survival Overall survival at five years Death
31.6 months [0;41.42] 10 (9%) 1 (0.9%) 9 (8.1%) 93.2% [83.4%; 97.2%] 98.3% [88.9%; 99.7%] 1 (0.9%)
Please cite this article in press as: Paillocher N, et al., Evaluation of mastectomy with immediate autologous latissimus dorsi breast reconstruction following neoadjuvant chemotherapy and radiation therapy: A single institution study of 111 cases of invasive breast carcinoma, Eur J Surg Oncol (2016), http://dx.doi.org/10.1016/j.ejso.2016.03.024
N. Paillocher et al. / EJSO xx (2016) 1e7
5
Surgical complications
Table 5 Satisfaction survey. Total N ¼ 74 Survey participation rate 67.3% Average satisfaction score 17/20 Do you have any criticisms concerning IBR: No 22 (29.7%) Yes 33 (44.6%) Please specify: (multiple-choice questions) Painful 10 (13.5%) Problem of symmetry 7 (9.5%) Volume problem 5 (6.7%) Problem of nipple areola complex 4 (5.4%) Problem of shape 3 (4%) Prominent axilla protuberance 1 (1.3%) Muscle contraction of flap 1 (1.3%) Necrosis 1 (1.3%) Poor clinical course over several years 1 (1.3%) Do you have back problems? No 32 (51.6%) Please specify: (multiple-choice questions) Dorsal pain 10 (16.1%) Aesthetically unpleasant scars 2 (3.2%) Adhesion 16 (25.8%) Seroma requiring draining 2 (3.2%) Would you like to undergo another procedure to improve the cosmetic result? Yes 16 (21.9%) No 57 (78%) Has the nippleeareola complex been reconstructed? Yes 41 (66.2%) - Satisfied 38 (92.7%) - Dissatisfied 3 (7.3%) No 33 (45.2%) - No required 26 (78.8%) Symmetrisation of contralateral breast? Yes 29 (40.3%) - Satisfied 26 (89.6%) - Dissatisfied 1 (3.4%) - No response 2 (6.89%) No 45 (59.7%) Would you do anything differently? No, i would have the same treatment 52 (70.3%) IBR but with a different technique 22 (29.7%) Wait a few monts after the mastectomy before DBR 1 (1.35%) No reconstruction 1 (1.35%) Adequate information supplied 70 (94.6%) Adequate reflection period 70 (94.6%) Have you been given support to accept the loss of your breast? Yes 69 (93.2%) No 3 (4%) No response 2 (2.7%) Have you been given support to accept your new body? Yes 66 (90%) No 5 (6.8%) No answer 2 (2.7%) Have you received sexuality support? Yes 45 (60.8%) No 16 (21.6%) Don’t know or no response 12 (16.2%)
according to the literature, smoking, obesity, diabetes and cardiovascular events are predictive factors associated with a lower capacity of healing and poorer aesthetic results.14,15
In this study, primary complications (excluding seroma) affected 10.8% of the patients. This concurred with the published date since Michy et al.11 reported a similar rate of 17.1% for primary complications. However, the production of seroma on donor site (former location of latissimus dorsi) was high (54%) whereas rates of 4.8% and 15.3% were reported by Monrigal et al.13 and Giacalone et al.16 respectively. The incidence of complications due to seroma production was previously reported to be high in approximately 80% of patients.17 In our study, preventive measures (such as fibrin sealants or Chippendale’s technique18) were not utilized. Our technique was described as an ALD flap (die-cut of the fascia superficialis), which could explain our high rate of seroma. Compared to the literature, our series showed a lower rate of necrosis (breast skin or donor site) (5.4%) than the studies of Giacalone et al.16 or Monrigal et al.13 who found 30.7% and 10% of dorsal necrosis or excess skin respectively. These outcomes lead us to presume that several surgical techniques may account for such differences in terms of necrotic complications. Our surgical procedure involved de-epidermisation of the latissimus dorsi flap.19 Our low rate of necrosis could be due to using the muscular flap, which could be helpful in the skin healing and nourishing process, by improving trophicity following RT treatment. Indeed, we believe that surgery performed between four to eight weeks after RT decreased the rate of flap and breast skin necrosis due to the acute local inflammatory response that enhanced blood flow as shown in the Hu et al. study.20 In this study,20 cutaneous blood flow through the irradiated breast, increased from 13.83 (5.01) perfusion units to 68.73 (57.70) perfusion units at the end of radiotherapy. It is now well documented that for many irradiated breast reconstructions, autologous reconstructions are the best choice in terms of aesthetic outcomes and risk management.21 In our study, cases of IBR for ipsilateral recurrence after lumpectomy and previous radiation were excluded in order to consider only recent pre-operative RT which ended a few weeks before surgery. We could therefore estimate the immediate, not long-term, side effects of RT on healing. As regards the IBR techniques, each one has its own indications. In the case of the radiation dose before surgery, we opted for the strategy that uses a latissimus dorsi (LD) flap for IBR but we did not contraindicate other techniques. The choice of surgery still has to meet the medical standards of oncological treatment, the patient’s physical condition and morphology and the patient’s wishes. However, as a mastectomy is known to be a traumatic event in a woman’s life, none of these factors should be considered as a contraindication for IBR. Nevertheless, information on morbidity, complication rates, and the impact of surgery on routine daily activities must be given to patients to
Please cite this article in press as: Paillocher N, et al., Evaluation of mastectomy with immediate autologous latissimus dorsi breast reconstruction following neoadjuvant chemotherapy and radiation therapy: A single institution study of 111 cases of invasive breast carcinoma, Eur J Surg Oncol (2016), http://dx.doi.org/10.1016/j.ejso.2016.03.024
6
N. Paillocher et al. / EJSO xx (2016) 1e7
enable them to decide whether or not they wish to undergo this type of surgical procedure. There are no significant differences between ALD and LDI in terms of early and delayed complications and surgical revision. The Monrigal et al. study13 showed that transverse rectus abdominis musculo-cutaneous (TRAM) flap and retropectoral implant (RI) reconstructions required more surgical revisions than LD reconstructions (RR TRAM vs LD ¼ 2.7 [1.4e5.3] and RR RI vs LD ¼ 4.2 [2.0e8.6], p ¼ 0.0006). Furthermore, Berry et al.22 found that radiation did not significantly impact upon complication rates (p ¼ 0.51 for total complications and p ¼ 0.79 for major complications) and showed that autologous tissue may be the best choice for reconstruction after RT (lower major complication rates compared to implant reconstruction). Our rate of capsular contracture was 2.7% which is considered low. The meta-analysis by Barry et al.23 demonstrated that autologous reconstruction is the best technique in terms of post-operative morbidity including capsular contracture. Furthermore, we think that placing the LD flap between the prostheses and skin that has undergone RT decreases the rate of capsular contractures. Patient satisfaction Patients who had IBR experienced less distress and better psychosocial well-being than those who had DBR.24,25 In the Giacalone et al. study,16 89% of patients were satisfied with the aesthetic result. This study compared two cohorts: one with 26 patients treated by CT, RT and then SSM and IBR with LDI and another with 78 patients undergoing a mastectomy followed by CT, RT and DBR. There was no significant difference between the two groups. A metaanalysis performed by Barry et al.23 confirmed the high patient satisfaction rate (natural appearance, psychosocial benefits, quality of life). The key to high quality patient care lies in the ability to respond to our patients’ needs and consistently frequent monitoring by the same medical care providers. The high patient satisfaction rate could be attributed to the reflection period prior to surgery, in addition to the surgical procedure (mastectomy and IBR), numerous consultations with the surgeon and the information given. This reflection period gave patients time to grieve for the loss of their breast. However, some patients criticized their IBR due to an unsatisfactory aesthetic outcome or dorsal after-effects. Therefore it appears essential to inform patients of the potential risk of complications (loss of sensitivity in the reconstructed breast,26 back pain, etc.) and how to manage them (importance of physiotherapy preventing poor posture and scar tissue adhesions). Patients need to be prepared by the surgeon for the aesthetic outcome (approximate symmetry, frequent need for surgical revision). The survey should remain anonymous to allow each patient to voice criticisms or express her wishes about medical care. The results of our satisfaction questionnaire
showed several expressions of gratitude and high satisfaction rates in terms of the cosmetic result. The high survey participation rate showed that patients were looking forward to sharing their opinions on the personal aspects of benefitting from an IBR. Obviously, the results could be improved by adding an approved questionnaire such as the BREAST e Q test but as this was a retrospective study over 10 years, we chose a simpler questionnaire in order to obtain the maximum number of responses. Oncological follow-up Our aim objective was to estimate the disease-free period and overall survival rates in patients who underwent this therapeutic sequence. With a median follow-up of 31.6 months, we noticed only one local recurrence of ductal carcinoma after seven years of follow-up for a lobular carcinoma treated by IBR without SSM. In terms of the overall survival rate, the literature highlighted a survival rate of 75% in the Michy et al. study11. In our study, the five year overall survival rate was higher (93.2%). Giacalone et al.16 reported a local recurrence rate of 7.7% after a median follow-up of 4.1 years for stage two and stage three patients who benefitted from pre-operative CT and RT prior to reconstruction by SSM and LDI. Monrigal et al.13 did not report any significant difference in terms of local recurrence and regional nodal recurrence, which leads us to believe that this strategy does not alter locoregional tumour control. Conclusion This phase II study assesses the feasibility and morbidity of SSM and IBR with an LD flap after NACT and RT in invasive breast carcinoma (M-RIC). To confirm our observations, other studies should be carried out, such as prospective studies comparing two groups (pre- and postoperative radiation and reconstruction) to evaluate the superiority of one of the therapeutic sequences. We are looking forward to the conclusion of the French multicentric clinical trial (M-RIC), in which our department participated in 2012. The results of this trial should be published shortly. Conflicts of interest statement None.
References 1. Newman LA, Kuerer HM, Hunet KK, et al. Presentation, treatment, and outcome of local recurrence after skin-sparing mastectomy and immediate breast reconstruction. Ann Surg Oncol 1998;5:620–6. 2. Howard MA, Polo K, Pusic AL, et al. Breast cancer local recurrence after mastectomy and TRAM flap reconstruction: incidence and treatment options. Plast Reconstr Surg 2006;117:1381–6.
Please cite this article in press as: Paillocher N, et al., Evaluation of mastectomy with immediate autologous latissimus dorsi breast reconstruction following neoadjuvant chemotherapy and radiation therapy: A single institution study of 111 cases of invasive breast carcinoma, Eur J Surg Oncol (2016), http://dx.doi.org/10.1016/j.ejso.2016.03.024
N. Paillocher et al. / EJSO xx (2016) 1e7 3. Garbay JR, Saouma S, Marsiglia H. Progress in immediate breast reconstruction with skin sparing mastectomy. Ann Chir Plast Esthet 2008;53:199–207. 4. Slavin SA, Love SM, Goldwyn RM. Recurrent breast cancer following immediate reconstruction with myocutaneous flaps. Plast Reconstr Surg 1994;93:1191–207. 5. Kroll SS, Khoo A, Singletary SE, et al. Local recurrence risk after skin-sparing and conventional mastectomy: a 6-year follow-up. Plast Reconstr Surg 1999;104(2):421–5. 6. McKeown DJ, Hogg FJ, Brown MJ, et al. The timing of autologous latissimus dorsi breast reconstruction and effect of radiotherapy on outcome. Plast Reconstr Surg 2009;62:488–93. 7. Gouy S, Rouzier R, Missana, et al. Immediate reconstruction after neoadjuvant chemotherapy: effect on adjuvant treatment starting and survival. Ann Surg Oncol 2005;12(2):161–6. 8. Knottenbelt A, Spauwen PH, Wobbes T. The oncological implications of immediate breast reconstruction. Eur J Surg Oncol 2004;30(8):829– 33. 9. Agence nationale d’accreditation et d’evaluation en sante. Chirurgie des lesions mammaires : prise en charge de premiere intention. Paris: ANAES; 2002. 10. Kontos M, Lewis RS, L€uchtenborg M, et al. Does immediate breast reconstruction using free flaps lead to delay in the administration of adjuvant chemotherapy for breast cancer? Eur J Surg Oncol 2010; 36:745–9. 11. Michy T, Gimbergues P, Le Bou€edec G, et al. What surgical procedure for immediate breast reconstruction after preoperative radiotherapy and chemotherapy? J Chir 2007;144(6):511–5. 12. Taylor CW, Kumar S. The effect of immediate breast reconstruction on adjuvant chemotherapy. Breast 2005;14(1):18–21. 13. Monrigal E, Dauplat J, Gimbergues P, et al. Mastectomy with immediate breast reconstruction after neoadjuvant chemotherapy and radiation therapy. A new option for patients with operable invasive breast cancer. Results of 20 years single institution study. EJSO 2011;(37): 864–70. 14. Chang DW, Reece GP, Wang B, et al. Effect of smoking on complications in patients undergoing free TRAM flap breast reconstruction. Plast Reconstr Surg 2000 Jun;105(7):2374–80. 15. Chang DW, Wang B, Robb GL, et al. Effect of obesity on flap and donor e site complications in free transverse rectus abdominis
16.
17.
18.
19.
20.
21.
22.
23. 24.
25.
26.
7
myocutaneous flap breast reconstruction. Plast Reconstr Surg 2000 Apr;105(5):1640–8. Giacalone PL, Rathat G, Daures JP, et al. New concept for immediate breast reconstruction for invasive cancers: feasibility, oncological safety and esthetic outcome of post-neoadjuvant therapy immediate breast reconstruction versus delayed breast reconstruction: a prospective pilot study. Breast Cancer Res Treat 2010;122:439–51. Lee KT, Mun GH. Fibrin sealants and quilting suture for prevention of seroma formation following latissimus dorsi muscle harvest: a systematic review and meta-analysis. Aesthetic Plast Surg 2015 Jun;39(3): 399–409. Gisquet H, Delay E, Paradol PO, et al. Prevention of seroma by quilting suture after harvesting latissimus dorsi flap. The “Chippendale” technique. Ann Chir Plast Esthet 2010 Apr;55(2):97–103. Delbaere M, Delaporte T, Toussoun G, et al. Skin e sparing mastectomy: how to avoid skin necrosis? Ann Chir Plast Esthet 2008;53: 208–25. Sc Hu, Hou MF, Luo KH, et al. Changes in biophysical properties of the skin following radiotherapy for breast cancer. J Dermatol 2014 Dec;41(12):1087–94. Spear SL, Boehmler JH, Taylor NS, Prada C. The role of the latissimus dorsi flap in reconstruction of the irritatied breast. Plast Reconstr Surg 2007 Jan;119(1):1–9. Berry MD, Brooks MD, Sydow MD, et al. Complications rates of radiation on tissue expander and autologous tissue breast reconstruction. Ann Surg Oncol 2010;17:S202–10. Barry M, Kell MR. Radiotherapy and breast reconstruction: a metaanalysis. Breast Cancer Res Treat 2011;127:15–22. Al-Ghazal SK, Fallowfield L, Blamey RW. The psychological impact of immediate rather than delayed breast reconstruction. Eur J Surg Oncol 2000;26(1):17–9. Reefy S, Patani N, Anderson A, et al. Oncological outcome and patient satisfaction with skin-sparing mastectomy and immediate breast reconstruction: a prospective observation study. BMC Cancer 2010; 10:171. Delay E, Jorquera F, Lucas R, et al. Sensitivity of breasts reconstructed with the autologous latissimus dorsi flap. Plast Reconstr Surg 2000; 106(2):302–9.
Please cite this article in press as: Paillocher N, et al., Evaluation of mastectomy with immediate autologous latissimus dorsi breast reconstruction following neoadjuvant chemotherapy and radiation therapy: A single institution study of 111 cases of invasive breast carcinoma, Eur J Surg Oncol (2016), http://dx.doi.org/10.1016/j.ejso.2016.03.024