Postmastectomy Radiation Research Articles

D134. Comparison of Nipple-sparing Mastectomy versus Skin-sparing Mastectomy in Bilateral Implant-based Breast Reconstruction with Unilateral Radiotherapy: A Matched Cohort Study

PURPOSE: Nipple-sparing mastectomy (NSM) preserves natural nipple-areola complex and entire native breast skin with a goal of better cosmetic outcomes in breast reconstruction. In bilateral tissue expander (TE)/implant-based reconstruction requiring unilateral post-mastectomy radiotherapy (PMRT), progressive radiation-induced fibrosis can lead to increasing nipple asymmetry with cosmetic dissatisfaction. Thus, PMRT may ultimately negate the intended positive cosmetic value of NSM compared to skin-sparing mastectomy (SSM). This study compares, 1) surgical complications, 2) patient satisfaction, and 3) aesthetic outcomes between NSM vs. SSM in bilateral implant-based reconstruction with unilateral PMRT. METHOD: This retrospective matched cohort study included consecutive NSM patients with TE/implant breast reconstruction + unilateral PMRT matched 1:2 to SSM group. All patients completed PMRT and TE exchange to implants. Demographics, oncologic stage, co-morbidities, and complication data were collected. Patient satisfaction was evaluated by BREAST-Q. Aesthetic outcome was assessed by blinded reviewers with a 5-point Likert scale. RESULTS: Among 58 patients who underwent bilateral TE/implant reconstruction with unilateral PMRT, 17 NSM patients were matched to 41 SSM patients by age, BMI, and co-morbidities. No significant difference existed between overall surgical complications (p=0.2) and BREAST-Q questionnaire scores. The average adverse effects of radiation score was higher in the NSM. Preliminary aesthetic outcomes demonstrated higher total average aesthetic score in SSM compared to NSM. CONCLUSION: Although NSM is generally associated with better cosmetic outcome compared to SSM, it has far less impact in bilateral implant-based breast reconstruction with unilateral PMRT. This may be related to the additional negative post-radiotherapy impact on nipple asymmetry.

D91. Effect of Pre-pectoral Versus Sub-pectoral Implant Placement in Breast Reconstruction on the Delivery of Post-mastectomy Radiation

PURPOSE: The placement of breast implants in a pre-pectoral compared to sub-pectoral plane has become increasingly popular in breast reconstruction, though data are limited on how this affects radiation delivery for locoregional disease control in women with breast cancer. This study aims to assess the dosimetric implications of implant location in women undergoing post-mastectomy radiation therapy (PMRT) after immediate breast reconstruction. METHODS: Patients with breast cancer treated with mastectomy, implant breast reconstruction, and PMRT between 2014-2022 at a single center were included. All patients received either intensity-modulated or 3-D conformal radiation therapy over an average of 5 weeks. Demographic, clinical and treatment data were collected through chart review. Patients were matched 1:1 on cancer sidedness, use of boost, fractionation and extent of radiation fields. Groups were compared using Mann-Whitney U or t-tests for continuous variables, and chi-square or Fisher’s Exact tests for categorical variables, as appropriate. RESULTS: Twenty-seven patients with pre-pectoral and 26 patients with sub-pectoral implants were included. Patients with pre-pectoral reconstruction had lower average implant volumes (452cc vs 503cc) prior to radiation. There was no difference in chest wall coverage (p=0.107), internal mammary node coverage (p=0.215), heart dose (p=0.627) or lung V20Gy (p=0.774). CONCLUSION: In this assessment of radiotherapeutic dosimetry in patients undergoing immediate breast reconstruction, we found no significant difference in target coverage or normal tissue dose based on pre- versus sub-pectoral implant location. This suggests that implant placement can be selected to optimize reconstructive outcomes, without concern for compromise to the oncologic quality of PMRT.

61. Wise-pattern Versus Transverse Pattern Mastectomy in Two-stage Implant-Based Breast Reconstruction: A Propensity Score-matched Analysis

PURPOSE: The wise pattern adapted to the mastectomy incisions has become a valuable asset for breast reconstruction in patients with large and ptotic breasts. Herein, we compared the time for exchange, time to initiate postmastectomy radiotherapy (PMRT) and complications rate between reconstructions performed with wise pattern versus a transverse incision pattern. METHODS: We retrospectively reviewed the record of patients who underwent immediate two-stage implant-based reconstruction (IBBR) between January 2011 and December 2020. Two cohorts were compared according to the incision pattern: wise versus transverse incision pattern. Complications were compared after propensity score matching. RESULTS: We initially analyzed 393 two-stage immediate IBBR in 239 patients, 91 (23.2%) in the wise-pattern group and 302 (76.8%) in the transverse pattern group. The expansion time (53 days versus 50 days, p=0.9), the time for TE-to-implant exchange (154 versus 175 days, p=0.547), and the time to initiate PMRT (144 days versus 126 days, p=0.616) were not different between groups. Before propensity score matching, the 30-day rate of wound-related complications (32% versus 10%, p<.001) and 30-day rate of wound complications requiring E/D+C procedures (20% versus 7%, p<.001) were significantly higher in the wise-pattern group. After propensity score matching, the 30-day rate of wound-related complications persisted significantly higher (25% versus 10%, p=0.03) in the wise-pattern group. CONCLUSION: The wise pattern mastectomy independently increases the incidence of wound-related complications versus only transverse patterns during two-stage IBBR, even after propensity score matching. Delayed TE placement may improve the safety profile of this procedure.

PC60. Impact of Postmastectomy Radiotherapy on Complications Following Prepectoral vs Subpectoral Breast Reconstruction

PC60. Impact of Postmastectomy Radiotherapy on Complications Following Prepectoral vs Subpectoral Breast Reconstruction

Dosimetric characterization of single- and dual-port temporary tissue expanders for postmastectomy radiotherapy using Monte Carlo methods.

The aim of this work was two-fold: a) to assess two treatment planning strategies for accounting CT artifacts introduced by temporary tissue-expanders (TTEs); b) to evaluate the dosimetric impact of two commercially available and one novel TTE. The CT artifacts were managed using two strategies. 1) Identifying the metal in the RayStation treatment planning software (TPS) using image window-level adjustments, delineate a contour enclosing the artifact, and setting the density of the surrounding voxels to unity (RS1). 2) Registering a geometry template with dimensions and materials from the TTEs (RS2). Both strategies were compared for DermaSpan, AlloX2, and AlloX2-Pro TTEs using Collapsed Cone Convolution (CCC) in RayStation TPS, Monte Carlo simulations (MC) using TOPAS, and film measurements. Wax slab phantoms with metallic ports and breast phantoms with TTEs balloons were made and irradiated with a 6 MV AP beam and partial arc, respectively. Dose values along the AP direction calculated with CCC (RS2) and TOPAS (RS1 and RS2) were compared with film measurements. The impact in dose distributions was evaluated with RS2 by comparing TOPAS simulations with and without the metal port. For the wax slab phantoms, the dose differences between RS1 and RS2 were 0.5% for DermaSpan and AlloX2 but 3% for AlloX2-Pro. From TOPAS simulations of RS2, the impact in dose distributions caused by the magnet attenuation was (6.4 ± 0.4) %, (4.9 ± 0.7)%, and (2.0 ± 0.9)% for DermaSpan, AlloX2, and AlloX2-Pro, respectively. With breast phantoms, maximum differences in DVH parameters between RS1 and RS2 were as follows. For AlloX2 at the posterior region: (2.1 ± 1.0)%, (1.9 ± 1.0)% and (1.4 ± 1.0)% for D1, D10, and average dose, respectively. For AlloX2-Pro at the anterior region (-1.0 ± 1.0)%, (-0.6 ± 1.0)% and (-0.6 ± 1.0)% for D1, D10 and average dose, respectively. The impact in D10 caused by the magnet was at most (5.5 ± 1.0)% and (-0.8 ± 1.0)% for AlloX2 and AlloX2-Pro, respectively. Two strategies for accounting for CT artifacts from three breast TTEs were assessed using CCC, MC, and film measurements. This study showed that the highest differences with respect to measurements occurred with RS1 and can be mitigated if a template with the actual port geometry and materials is used.

Post-mastectomy radiation therapy in HER-2 positive breast cancer after primary systemic therapy: Pooled analysis of TRYPHAENA and NeoSphere trials

PurposeThe role of post-mastectomy radiation therapy (PMRT) following primary systemic therapy (PST) in HER-2 positive breast cancer (Her2 + BC) remains poorly understood. The current study evaluates PMRT based on the pathological response to PST in Her2 + BC. Methods and materialsTRYPHAENA and NeoSphere are randomized phase II trials that investigated PST for Her2 + BC. Our study is a pooled analysis of both trials, including 312 node-positive patients treated with HER-2 targeted PST followed by mastectomy with or without PMRT. The primary endpoint is loco-regional recurrence-free survival (LRRFS). ResultsOur analysis included 172 (55%) patients who achieved complete nodal pathological response (ypN0) and 140 (45%) patients who did not. Patients with ypN0 had a 5-year LRRFS of 97% in both, the PMRT and no PMRT, groups (p = 0.94). Patients with ypN + had 5-year LRRFS of 89% in the PMRT group and 82% in the no PMRT group (p = 0.17). Patients with ypN1 (n = 62) disease who received PMRT (n = 40) had a 5-year LRRFS of 85% as compared to 89% in those who did not (n = 22); (p = 0.60). A significant LRRFS difference was noted in patients with ypN2-3 (n = 78) disease who received PMRT (n = 53) compared to those who did not (n = 25) (5-year LRRFS 92% vs. 75%; p = 0.019). On multivariate analysis, clinical nodal disease at diagnosis and ypN0 were significantly associated with loco-regional recurrence (LRR). ConclusionsHer2 + BC patients who achieve ypN0 after PST have excellent locoregional-control which supports de-escalation of PMRT. In contrast, patients with ypN2-3 disease derive significant benefit from PMRT. Clinical nodal stage at presentation and ypN0 status are significantly associated with LRR risk in Her2 + BC.

Effect of internal port on dose distribution in post-mastectomy radiotherapy for breast cancer patients after expander breast reconstruction.

In patients with expander-based reconstruction a few dosimetric analyses detected radiation therapy dose perturbation due to the internal port of an expander, potentially leading to toxicity or loss of local control. This study aimed at adding data on this field. A dosimetric analysis was conducted in 30 chest wall treatment planning without and with correction for port artifact. In plans with artifact correction density was overwritten as 1 g/cm3. Medium, minimum and maximum chest wall doses were compared in the two plans. Both plans, with and without correction, were compared on an anthropomorphic phantom with a tissue expander on the chest covered by a bolus simulating the skin. Ex vivo dosimetry was carried out on the phantom and in vivo dosimetry in three patients by using film strips during one treatment fraction. Estimated doses and measured film doses were compared. No significant differences emerged in the minimum, medium and maximum doses in the two plans, without and with correction for port artifacts. Ex vivo and in vivo analyses showed a good correspondence between detected and calculated doses without and with correction. The port did not significantly affect dose distribution in patients who will receive post-mastectomy radiation therapy.

A Machine Learning Approach for Predicting Capsular Contracture after Postmastectomy Radiotherapy in Breast Cancer Patients

In recent years, immediate breast reconstruction after mastectomy surgery has steadily increased in the treatment pathway of breast cancer (BC) patients due to its potential impact on both the morpho-functional and aesthetic type of the breast and the quality of life. Although recent studies have demonstrated how recent radiotherapy techniques have allowed a reduction of adverse events related to breast reconstruction, capsular contracture (CC) remains the main complication after post-mastectomy radio-therapy (PMRT). In this study, we evaluated the association of the occurrence of CC with some clinical, histological and therapeutic parameters related to BC patients. We firstly performed bivariate statistical tests and we then evaluated the prognostic predictive power of the collected data by using machine learning techniques. Out of a sample of 59 patients referred to our institute, 28 patients (i.e., 47%) showed contracture after PMRT. As a result, only estrogen receptor status (ER) and molecular subtypes were significantly associated with the occurrence of CC after PMRT. Different machine learning models were trained on a subset of clinical features selected by a feature importance approach. Experimental results have shown that collected features have a non-negligible predictive power. The extreme gradient boosting classifier achieved an area under the curve (AUC) value of 68% and accuracy, sensitivity, and specificity values of 68%, 64%, and 74%, respectively. Such a support tool, after further suitable optimization and validation, would allow clinicians to identify the best therapeutic strategy and reconstructive timing.

Subpectoral Implant Placement Is Not Protective against Postmastectomy Radiotherapy-Related Complications Compared to Prepectoral Placement.

Postmastectomy radiotherapy (PMRT) is associated with altered cosmetic outcomes and higher complication rates in implant-based breast reconstruction (IBR). Conventional wisdom suggests that muscle coverage is somewhat protective against PMRT-related complications. In this study, the authors compared surgical outcomes in patients who underwent two-stage prepectoral versus subpectoral IBR in the setting of PMRT. The authors performed a retrospective cohort study of patients who underwent mastectomy and PMRT with two-stage IBR from 2016 to 2019. The primary outcome was breast-related complications, including device infection; the secondary outcome was device explantation. The authors identified 179 reconstructions (101 prepectoral and 78 subpectoral) in 172 patients with a mean follow-up time of 39.7 ± 14.4 months. There were no differences between the prepectoral and subpectoral reconstructions in rates of breast-related complications (26.7% and 21.8%, respectively; P = 0.274), device infection (18.8% and 15.4%, respectively; P = 0.307), skin flap necrosis (5.0% and 1.3%, respectively; P = 0.232), or device explantation (20.8% and 14.1%, respectively; P = 0.117). In adjusted models, compared with prepectoral device placement, subpectoral device placement was not associated with a lower risk of breast-related complications [hazard ratio (HR), 0.75; 95% confidence interval (CI), 0.41 to 1.36], device infection (HR, 0.73; 95% CI, 0.35 to 1.49), or device explantation (HR, 0.58; 95% CI, 0.28 to 1.19). Device placement plane was not predictive of complication rates in IBR in the setting of PMRT. Two-stage prepectoral IBR provides safe long-term outcomes with acceptable postoperative complication rates comparable to those with subpectoral IBR, even in the setting of PMRT. Therapeutic, III.

Prevention of Postoperative Complications by Prepectoral versus Subpectoral Breast Reconstruction: A Systematic Review and Meta-Analysis.

Implant-based breast reconstruction has evolved over time. However, the effects of prepectoral breast reconstruction (PBR) compared with those of subpectoral breast reconstruction (SBR) have not been clearly defined. Therefore, this study aimed to compare the occurrence of surgical complications between PBR and SBR to determine the procedure that is effective and relatively safe. The PubMed, Cochrane Library, and EMBASE databases were searched for studies published until April of 2021 comparing PBR and SBR following mastectomy. Two authors independently assessed the risk of bias. General information on the studies and surgical outcomes were extracted. Among 857 studies, 34 and 29 were included in the systematic review and meta-analysis, respectively. Subgroup analysis was performed to clearly compare the results of patients who underwent postmastectomy radiation therapy. Pooled results showed that prevention of capsular contracture (OR, 0.57; 95% CI, 0.41 to 0.79) and infection control (OR, 0.73; 95% CI, 0.58 to 0.92) were better with PBR than with SBR. Rates of hematoma, implant loss, seroma, skin-flap necrosis, and wound dehiscence were not significantly different between PBR and SBR. PBR considerably improved postoperative pain, BREAST-Q score, and upper arm function compared with SBR. Among postmastectomy radiation therapy patients, the incidence rates of capsular contracture were significantly lower in the PBR group than in the SBR group (OR, 0.14; 95% CI, 0.05 to 0.35). The results showed that PBR had fewer postoperative complications than SBR. The authors' meta-analysis suggests that PBR could be used as an alternative technique for breast reconstruction in appropriate patients.

Can knowledge based treatment planning of VMAT for post-mastectomy locoregional radiotherapy involving internal mammary chain and supraclavicular fossa improve performance efficiency?

To validate and evaluate the performance of knowledge-based treatment planning for Volumetric Modulated Arc Radiotherapy for post-mastectomy loco-regional radiotherapy. Two knowledge-based planning (KBP) models for different dose prescriptions were built using the Eclipse RapidPlanTM v 16.1 (Varian Medical Systems, Palo Alto, USA) utilising the plans of previously treated patients with left-sided breast cancer who had undergone irradiation of the left chest wall, internal mammary nodal (IMN) region and supra-clavicular fossa (SCF). Plans of 60 and 73 patients were used to generate the KBP models for the prescriptions of 40 Gy in 15 fractions and 26 Gy in 5 fractions, respectively. A blinded review of all the clinical plans (CLI) and KBPs was done by two experienced radiation oncology consultants. Statistical analysis of the two groups was also done using the standard two-tailed paired t-test or Wilcoxon signed rank test, and p<0.05 was considered significant. A total of 20 metrics were compared. The KBPs were found to be either better (6/20) or comparable (10/20) to the CLIs for both the regimens. Dose to heart, contralateral breast,contralateral lung were either better or comparable in the KBP plans except of ipsilateral lung. Mean dose (Gy) for the ipsilateral lung are significantly (p˂0.001) higher in KBP though the values were acceptable clinically. Plans were of similar quality as per the result of the blinded review which was conducted by slice-by-slice evaluation of dose distribution for target coverage, overdose volume and dose to the OARs. However, it was also observed that treatment times in terms of monitoring units (MUs) and complexity indices are more in CLIs as compared with KBPs (p<0.001). KBP models for left-sided post-mastectomy loco-regional radiotherapy were developed and validated for clinical use. These models improved the efficiency of treatment delivery as well as work flow for VMAT planning involving both moderately hypo fractionated and ultra-hypo fractionated radiotherapy regimens.

Dosimetry Evaluation of Treatment Planning Systems in Patient-Specific 3D Printed Anthropomorphic Phantom for Breast Cancer after Mastectomy using a Single-Beam 3D-CRT Technique for Megavoltage Electron Radiation Therapy.

The patient-specific 3D printed anthropomorphic phantom is used for breast cancer after mastectomy developed by the laboratory of medical physics and biophysics, Department of Physics, Institut Teknologi Sepuluh Nopember, Indonesia. This phantom is applied to simulate and measure the radiation interactions occurring in the human body either using the treatment planning system (TPS) or direct measurement with external beam therapy (EBT) 3 film. This study aimed to provide dose measurements in the patient-specific 3D printed anthropomorphic phantom using a TPS and direct measurements using single-beam three-dimensional conformal radiation therapy (3DCRT) technique with electron energy of 6 MeV. In this experimental study, the patient-specific 3D printed anthropomorphic phantom was used for post-mastectomy radiation therapy. TPS on the phantom was conducted using a 3D-CRT technique with RayPlan 9A software. The single-beam radiation was delivered to the phantom with an angle perpendicular to the breast plane at 337.3° at 6 MeV with a total prescribed dose of 5000 cGy/25 fractions with 200 cGy per fraction. The doses at planning target volume (PTV) and right lung confirmed a non-significant difference both for TPS and direct measurement with P-values of 0.074 and 0.143, respectively. The dose at the spinal cord showed statistically significant differences with a P-value of 0.002. The result presented a similar skin dose value using either TPS or direct measurement. The patient-specific 3D printed anthropomorphic phantom for breast cancer after mastectomy on the right side has good potential as an alternative to the evaluation of dosimetry for radiation therapy.

Development and validation of nomograms for predicting survival outcomes in patients with T1-2N1 breast cancer to identify those who could not benefit from postmastectomy radiotherapy.

In this study, we aimed to develop and validate nomograms for predicting the survival outcomes in patients with T1-2N1 breast cancer to identify the patients who could not benefit from postmastectomy radiotherapy (PMRT). Data from 10191 patients with T1-2N1 breast cancer were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Of them, 6542 patients who had not received PMRT formed the training set. Concurrently, we retrospectively enrolled 419 patients from the Affiliated Hospital of North Sichuan Medical College (NSMC), and 286 patients who did not undergo PMRT formed the external validation set. The least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analyses were used for selecting prognostic factors in the training set. Using the selected factors, two prognostic nomograms were constructed. The nomograms' performance was assessed using the concordance index (C-index), calibration curves, decision curve analysis (DCA), and risk subgroup classification. The stabilized inverse probability of treatment weights (IPTWs) was used to balance the baseline characteristics of the different risk groups. Finally, the survival outcomes and effectiveness of PMRT after IPTW adjustment were evaluated using adjusted Kaplan-Meier curves and Cox regression models. The 8-year overall survival (OS) and breast cancer-specific survival (BCSS) rates for the SEER cohort were 84.3% and 90.1%, with a median follow-up time of 76 months, while those for the NSMC cohort were 84.1% and 86.9%, with a median follow-up time of 73 months. Moreover, significant differences were observed in the survival curves for the different risk subgroups (P < 0.001) in both SEER and NSMC cohorts. The subgroup analysis after adjustment by IPTW revealed that PMRT was significantly associated with improved OS and BCSS in the intermediate- (hazard ratio [HR] = 0.72, 95% confidence interval [CI]: 0.59-0.88, P=0.001; HR = 0.77, 95% CI: 0.62-0.95, P = 0.015) and high- (HR=0.66, 95% CI: 0.52-0.83, P<0.001; HR=0.74, 95% CI: 0.56-0.99, P=0.039) risk groups. However, PMRT had no significant effects on patients in the low-risk groups. According to the prognostic nomogram, we performed risk subgroup classification and found that patients in the low-risk group did not benefit from PMRT.

The use of a wearable cardioverter defibrillator during postmastectomy radiotherapy as an alternative for relocation of the pulse generator

We describe a case in which a breast cancer patient with an implantable cardioverter-defibrillator (ICD) was treated with postmastectomy followed by axillary radiation therapy. The ICD was partly within the target volume and according to the treatment planning system would receive a maximum dose of about 36 Gy. Postoperatively, the patient had a wound infection needing surgical intervention and 3 months of antibiotics. Therefore, it was decided not to relocate the ICD but instead to switch off the shock function of the ICD for the entire radiation therapy course. The ICD was successfully substituted with a wearable cardioverter defibrillator (WCD), which the patient wore during the 3-week radiation therapy period until 2 weeks after the end of treatment. The ICD function was monitored from the start of the treatment until 6 months after treatment. In situations in which an ICD needs to be switched off semipermanently, a WCD can be used as alternative. The patient in this report tolerated the WCD well. Despite the high dose received by the ICD, the device and its battery continued to function normally.

Breast cancer status, grading system, etiology, and challenges in Asia: an updated review

Abstract The number of breast cancer incidences reported worldwide has increased tremendously over the years. Scoping down to Asia, in 2020, the reported incidences of breast cancer are appalling, comprising 1,026,171 cases, occupying up to 45.4% of cases across the globe. Breast cancer is a non-communicable disease, that emerges in variegated forms, self-subsistent, and the etiology is observed to be multifactorial, dependent on the individual reproductive pattern, hormonal factors, diet, physical activity, lifestyle, and exposure to certain advent procedures. Given this complexity, breast cancer is expected to undergo a persistent increment in the number of incidences in near future, exacerbating the public health quality, regardless of race, ethnicity, geographical subgroups, and socioeconomic. In this review article, the authors examine breast cancer in multiple facets, comprising the updated statistics on breast cancer, typically in Asia; etiology of breast cancer; diagnosis of breast cancer; grading system; and challenges in breast cancer from the country’s income perspective. Realizing the ever-increasing demand for quality treatment, here, the article also contemplates common therapies in breast cancer, such as breast-conserving therapy, mastectomy, postmastectomy radiation therapy, neoadjuvant chemotherapy, axillary surgery, chemotherapy, adjuvant medical therapies, biological and targeted therapies, and endocrine therapy. This review article intended to provide a brief yet broad panoramic view of breast cancer, to readers, ranging from newcomers, existing researchers, and relevant stakeholders in the topic of interest.

Surgical Outcomes Of Post-Mastectomy Radiotherapy Following Immediate Prosthetic Breast Reconstruction: Six-Year Experience

Surgical Outcomes Of Post-Mastectomy Radiotherapy Following Immediate Prosthetic Breast Reconstruction: Six-Year Experience

Nipple Projection Change in Immediate Breast Reconstruction and Use of an Acellular Dermal Matrix Strut for Maintaining Nipple Projection.

Nipple-sparing mastectomy (NSM) has gained popularity as more studies have supported its oncologic safety. Although there have been some studies reporting complications including mastectomy flap and nipple necrosis, there have been few reports discussing the change in nipple projection following NSM. This study aimed to analyze the change in nipple projection after NSM and identify risk factors for nipple depression. In addition, the authors present a new method for maintaining nipple projection. Patients who underwent NSM between March of 2017 and December of 2020 at the authors' institute were included in this study. The authors measured the preoperative and postoperative nipple projection height and used a nipple projection ratio (NPR) to compare the change in height. Univariate and multivariate analyses were performed to examine the correlation of variables with the NPR. A total of 307 patients and 330 breasts were included in this study. There were 13 cases of nipple necrosis. The postoperative nipple height was decreased by 32.8%, which was statistically significant. In multiple linear regression analysis, the use of an acellular dermal matrix strut was positively correlated with the NPR and implant-based reconstruction and postmastectomy radiation therapy were negatively correlated with the NPR. The results of this study demonstrated that the reduction in nipple height after NSM was statistically significant. Surgeons need to be aware of these changes following NSM and explain this possibility to patients who have risk factors. The application of an acellular dermal matrix strut should be considered for the prevention of nipple reduction. Therapeutic, III.

Abstract GS4-05: Phase II randomized trial of conventional versus hypofractionated post-mastectomy proton radiotherapy

Abstract Purpose/Objectives: Proton therapy is under investigation in breast cancer as a strategy to reduce heart and lung exposure, which is associated with late cardiopulmonary adverse events and secondary malignancy. To date, studies investigating postmastectomy radiotherapy (PMRT) with protons have used conventional fractionation. We hypothesized that condensing treatment to 15 fractions would be safe based on evidence that breast cancer is more sensitive to higher dose fractions than surrounding normal tissues. Materials/Methods: We conducted a randomized non-inferiority phase II trial comparing conventional and hypofractionated proton PMRT with primary endpoint of 24-month complication rate (defined as grade 3 or higher late adverse events using CTCAE, v 4.0 and/or unplanned surgical intervention in patients undergoing mastectomy with reconstruction). With a 10% non-inferiority margin the study ensured 80% power and had a one sided-type I error rate of 0.05. Cardiotoxicity was assessed with serial transthoracic conventional and 2-dimensional speckle tracking echocardiography (2D-STE). Eligibility included age ≥ 18 years with non-inflammatory breast cancer resected by mastectomy with indications for PMRT. Assignment of treatments was balanced with respect to immediate breast reconstruction (IBR). Conventional fractionation group received 50 Gy in 25 fractions of 2 Gy, and hypofractionation group received 40.05 Gy in 15 fractions of 2.67 Gy (RBE 1.1). Target volume included the chest wall and axillary, supraclavicular, and internal mammary lymph nodes. All patients were treated with multi-field optimized pencil beam scanning (intensity modulated proton therapy). Results: Between 2016 and 2018, 82 patients were enrolled and randomized (41 conventional, 41 hypofractionation). Median patient age was 52 years. 32.9% were staged T3-T4 and 79.3% node positive at diagnosis. 57 of 82 patients (69.5%) elected IBR. The median mean heart dose was 0.49 Gy and the median ipsilateral lung volume receiving 40% of prescription or greater (V40%) was 13.6%. No significant changes on conventional or 2D-STE at end-of-treatment or 3-month follow-up compared to baseline were observed. The rate of ≥ grade 2 acute dermatitis was lower with hypofractionation (44% vs 15%, p = 0.006). Other ≥ grade 2 acute adverse events including esophagitis (0 vs 5%), infection (5% vs 2.4%) and skin hyperpigmentation (7.3% vs 4.8%) were not significantly different between the two arms. With a median follow-up of 38.3 months, the 24-month complication rate was conventional 14.6% vs hypofractionation 17.1% (absolute difference 2.4%, p=0.17, 95% CI [-, 15.7%]). In patients with IBR, 6 of 28 (21.4%) conventional and 7 of 29 (24.1%) hypofractionated patients developed complications (p =0.80). There was no significant difference in 3-year disease-free survival between the conventional (89.4%; 95% CI 80.0 – 99.8%) and hypofractionated (92.4%, 95% CI 84.5 – 100.0%) arms (p = 0.91). One local recurrence occurred in the hypofractionated arm simultaneous with regional and distant relapse. The remaining 6 recurrences were isolated distant events. Conclusions: Proton PMRT provided excellent locoregional control and normal tissue sparing. There were no subclinical echocardiographic changes indicative of radiation-induced cardiac dysfunction. Hypofractionation resulted in comparable disease control, tolerability and reconstruction outcomes as conventional fractionation. Although non-inferiority of hypofractionation could not be established based on the upper bound of the 95% confidence interval for complication rate being greater than 10%, both conventional and hypofractionation may be considered appropriate regimens for ongoing phase 3 randomized trials comparing photon and proton radiotherapy. Citation Format: Robert Mutter, Sharmila Giri, Briant Fruth, Nicholas Remmes, Aman Anand, Kathryn Ruddy, Hector Villarraga, Sebastian Santos Patarroyo, Elizabeth Yan, Kenneth Merrell, Lisa McGee, Tamara Vern-Gross, Bradley Stish, Robert Gao, Judy C. Boughey, Sean Park, Kimberly Corbin, Carlos Vargas. Phase II randomized trial of conventional versus hypofractionated post-mastectomy proton radiotherapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr GS4-05.

Abstract P2-15-03: Impact of radiotherapy on the long-term patient-reported outcomes of immediate breast reconstruction: The UK Brighter

Abstract Introduction: Post-mastectomy radiotherapy (PMRT) is an important component of breast cancer treatment and has been shown to improve overall survival for women with large cancers or node positive disease. The long-term effects of radiotherapy on the outcomes of immediate breast reconstruction (IBR) and how these are perceived from the patients’ perspective, however, are largely unknown. The UK Brighter study aimed to evaluate the long-term impact of PMRT on the patient-reported outcomes of IBR to support informed decision-making. Methods: Women who underwent unilateral mastectomy and/or breast reconstruction for invasive breast cancer or ductal carcinoma in situ (DCIS) in England between 1/4/2008 and 31/3/2009 were identified from National Health Service (NHS) Hospital Episode Statistics (HES), and current contact information for the surviving cohort provided by the NHS Personal Demographic Service. Women were sent a letter inviting them to complete three validated patient-reported outcome questionnaires, the BREAST Q, EQ-5D-5L and ICECAP-A, electronically or by post at a minimum of 12 years following their index surgery. Questionnaires were scored according to developers’ instructions and scores for women who had received PMRT following IBR compared with those who underwent IBR without radiotherapy, in the cohort as a whole and by reconstruction type. Results: 11,977 women were invited to participate of whom 4,207 (35.1%) completed the questionnaires. Some 1,236 (29.4%) underwent IBR with 343 (27.8%) expander/implant (EI) reconstructions, 629 (50.9%) latissimus dorsi (LD) flaps with or without (+/-) an implant, and 264 (21.4%) abdominal flap (AF) reconstructions. Of these, 388 (31.4%) (EI n=79 (20.4%); LD+/-implant n=222 (57.2%); AF n=87 (22.4%) received PMRT. In the cohort overall, women who received PMRT following IBR reported significantly lower ‘Satisfaction with Breasts’ scores at 12 years compared with those who did not receive radiotherapy (PMRT mean 56.4. standard deviation (SD) 21.5 vs. no PMRT mean 61.3, SD 20.5), p&amp;lt; 0.001). However, this difference varied across procedure types. Specifically, the ‘Satisfaction with Breasts’ scores of women receiving PMRT following AF reconstruction were 10.5 points lower than those not receiving PMRT (PMRT mean 60.9, SD 20.2; no PMRT mean 71.4, SD 19.6, p&amp;lt; 0.001). This difference was lower in in women undergoing LD reconstruction (mean with PMRT 54.3, SD 21.1; mean without PMRT 61.6, SD 20.7; p&amp;lt; 0.001). There were no significant differences in women undergoing EI reconstruction (PMRT mean 57.5, SD 23.6, no PMRT mean 53.9, SD 17.7). ‘Physical Well-being’ (chest) scores were also significantly lower in women receiving PMRT following IBR in the cohort overall (PMRT mean 78.7, SD 20.1, no PMRT 83.6, SD 18.6, p&amp;lt; 0.001) but women undergoing AF reconstruction showed the greatest difference in scores (PMRT mean 83.2, SD 17.0 vs No PMRT mean 90.1, SD 15.0, p&amp;lt; 0.001). There were no significant differences in ‘Physical Well-being’ scores for women who underwent EI reconstruction with or without PMRT. ‘Psychosocial Well-being’ scores were lower in women receiving PMRT after IBR (PMRT mean 70.8, SD 22.0, No PMRT 75.4, SD 21.0), but again, differential effects were seen by procedure type with no significant differences seen in the EI group but significant differences in scores seen in women receiving PMRT after flap-based procedures. Conclusions: Women undergoing PMRT report significantly lower long-term patient-reported outcomes of flap-based reconstruction, in particular ‘Satisfaction with Breasts’ and ‘Physical Well-being’ scores. This difference was not apparent in women undergoing EI procedures. This information should be shared with patients to help them make fully informed decisions about the type and timing of their reconstructive surgery. Citation Format: Leigh Johnson, Paul White, Ranjeet Jeevan, John Browne, Carmel Gulliver-Clarke, Joe O’Donoghue, Syed Mohiuddin, William Hollingworth, Patricia Fairbrother, Mairead MacKenzie, Chris Holcombe, Shelley Potter. Impact of radiotherapy on the long-term patient-reported outcomes of immediate breast reconstruction: The UK Brighter [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-15-03.

Abstract PD6-10: PD6-10 The impact of post mastectomy radiation therapy on clinical outcomes of male breast cancer: A meta-analysis of comparative studies

Abstract Background/Rationale: Male breast cancer accounts for less than 1 percent of all cancer diagnoses in men. Because it is rare, it does not lend itself to large, randomized trials. In general, the approach to the treatment of early, non-metastatic male breast cancer has largely been extrapolated from female breast cancer trials. Specifically, the data on early-stage post mastectomy radiation therapy (PMRT) is limited, and its benefits remain unclear. Objectives: We conducted this meta-analysis to determine the impact of PMRT on clinical outcomes of men with breast cancer. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of English language, diagnosis of invasive non-metastatic male breast cancer (MBC), comparative studies of PMRT versus none, and studies that reported the incidence of local and distant recurrences as well as survival data in the compared arms. A meta-analysis using the Mantel-Haenszel method for calculating the weighted pooled relative risk (RR) under the fixed effects model. Subsequently, the heterogeneity statistic gets incorporated to calculate the summary RR under the random effects model. Results: Ten retrospective comparative studies with 3912 patients were included and analyzed. Eight studies reported survival data. Six and three studies reported local and distant recurrence incidence, respectively. PMRT did not have an impact on overall survival or distant recurrences. However, PMRT significantly lowered the RR of locoregional recurrences (RR=0.53, 95%CI 0.31-0.92). In addition, when survival was analyzed by TNM stage and N status, PMRT was found to have a significant reduction in RR of death in stage III (RR=0.85, 95%CI 0.75-0.97), N1 (RR=0.77, 95%CI 0.61-0.98), and N2 (RR=0.61, 95%CI 0.49-0.78) disease. Conclusions: This is the first meta-analysis to show that PMRT is associated with a lower relative risk of death in stage III MBC as well as N1 and N2 disease. It also demonstrates a significant reduction in RR of locoregional recurrences. In the absence of randomized clinical trials, it represents the most compelling data supporting the use of PMRT in this MBC patient population. Citation Format: Philip A. Haddad, Usman Zaheer. PD6-10 The impact of post mastectomy radiation therapy on clinical outcomes of male breast cancer: A meta-analysis of comparative studies [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD6-10.