A radiomic model to classify response to neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Medical image analysis has evolved to facilitate the development of methods for high-throughput extraction of quantitative features that can potentially contribute to the diagnostic and treatment paradigm of cancer. There is a need for further improvement in the accuracy of predictive markers of response to neo-adjuvant chemotherapy (NAC). The aim of this study was to develop a radiomic classifier to enhance current approaches to predicting the response to NAC breast cancer. METHODS: Data on patients treated for breast cancer with NAC prior to surgery who had a pre-NAC dynamic contrast enhanced breast MRI were included. Response to NAC was assessed using the Miller-Payne system on the excised tumor. Tumor segmentation was carried out manually under the supervision of a consultant breast radiologist. Features were selected using least absolute shrinkage selection operator regression. A support vector machine learning model was used to classify response to NAC. RESULTS: 74 patients were included. Patients were classified as having a poor response to NAC (reduction in cellularity < 90%, n = 44) and an excellent response (> 90% reduction in cellularity, n = 30). 4 radiomics features (discretized kurtosis, NGDLM contrast, GLZLM_SZE and GLZLM_ZP) were identified as pertinent predictors of response to NAC. A SVM model using these features stratified patients into poor and excellent response groups producing an AUC of 0.75. Addition of estrogen receptor status improved the accuracy of the model with an AUC of 0.811. CONCLUSION: This study identified a radiomic classifier incorporating 4 radiomics features to augment subtype based classification of response to NAC in breast cancer.

Preoperative Breast Magnetic Resonance Imaging as a Predictor of Response to Neoadjuvant Chemotherapy.

Introduction: The ability to accurately predict pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast cancer would improve patient selection for specific treatment strategies, would provide important information for patients to aid in the treatment selection process, and could potentially avoid the need for more extensive surgery. The diagnostic performance of magnetic resonance imaging (MRI) in predicting pCR has previously been studied, with mixed results. Magnetic resonance imaging performance may also be influenced by tumour and patient factors. Methods: Eighty-seven breast cancer patients who underwent NAC were studied. Pre-NAC and post-NAC MRI findings were compared with pathologic findings postsurgical excision. The impact of patient and tumour characteristics on MRI accuracy was evaluated. Results: The mean (SD) age of participants was 48.7 (10.3) years. The rate of pCR based on post-NAC MRI was 19.5% overall (19/87). The sensitivity, specificity, positive predictive value (PPV), negative predictive value, and accuracy in predicting pCR were 52.9%, 77.1%, 36.0%, 87.1%, and 72.4%, respectively. Positive predictive value was the highest in nonluminal versus Luminal A disease (45.0% vs 25.0%, P < .001), with higher rates of false positivity in nonluminal subtypes (P = .002). Tumour grade, T category, and histological subtype were all independent predictors of MRI accuracy regarding post-NAC tumour size. Conclusion: Magnetic resonance imaging alone is insufficient to accurately predict pCR in breast cancer patients post-NAC. Magnetic resonance imaging predictions of pCR are more accurate in nonluminal subtypes. Tumour grade, T category, and histological subtype should be considered when evaluating post-NAC tumour sizes.

Oncological Risk in Autologous Stem Cell Donation for Novel Tissue-Engineering Approaches to Postmastectomy Breast Regeneration.

Adipose tissue engineering using adipose-derived stem cells (ADSCs) has emerged as an opportunity to develop novel approaches to postmastectomy breast reconstruction with the potential for an autologous tissue source with a natural appearance and texture. As of yet, the role of ADSCs in breast cancer development and metastasis is not completely understood; therefore, we must consider the oncological safety of employing an autologous source of ADSCs for use in breast regeneration. This study investigated the regenerative properties of ADSCs isolated from breast cancer patients, including those who had received neoadjuvant chemotherapy, and noncancer controls. The ADSCs were characterised for several parameters central to tissue regeneration, including cell viability, proliferation, differentiation potential, and cytokine secretion. A stem cell population was isolated and confirmed by flow cytometry and multilineage differentiation. There was no difference in cell phenotype or surface antigen expression between ADSCs from different sources. Adipose-derived stem cells isolated from the breast of cancer patients exhibited reduced adipogenic differentiation potential compared with ADSCs from other sources. The greatest degree of adipogenic differentiation was observed in ADSCs isolated from the subcutaneous abdominal fat of noncancer controls. The proliferation rate of ADSCs isolated from the breast of cancer patients was increased compared with other sources; however, it was decreased in ADSCs isolated from breast cancer patients who had recently been treated with neoadjuvant chemotherapy. A number of cytokines were detected in the cell conditioned media of ADSCs from different sources, including matrix metalloproteinase-2 (MMP-2), which was detected at higher levels in the secretome of ADSCs from breast cancer patients compared with noncancer controls. This study provides important information relating to the suitability of ADSCs as an autologous cell source for adipose tissue engineering in postcancer reconstruction. Results indicate that while the surface phenotype does not differ, the differentiation capacity, proliferative rate, and secreted cytokine profile are affected by the presence or treatment of breast cancer. These findings support further investigation into the regenerative potential of these ADSCs, if they are to be considered in clinical reconstructive strategies.

A Review of the Impact of Neoadjuvant Chemotherapy on Breast Surgery Practice and Outcomes.

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is increasingly used in locally advanced breast cancer as it facilitates breast conserving surgery (BCS) and allows surgical treatment of patients considered inoperable at baseline. The aim of this study was to assess the trends in breast cancer management with regard to the administration of NAC and adjuvant chemotherapy and the effect this has on surgical practice, patient outcomes, and patterns of disease recurrence. PATIENTS AND METHODS: Patients treated with chemotherapy from 2005 to 2014 were identified from a prospectively maintained database. Clinicopathologic details, timing of chemotherapy delivery, and surgical procedures carried out were analyzed. RESULTS: A total of 1619 patients were included in the study. The NAC group (n = 383) had a higher T stage (P < .001) and higher grade disease than the adjuvant group (P = .017). Luminal A breast cancer was less likely to be treated by NAC. The proportion of patients treated with NAC has increased from 12.1% in 2005 to 48.3% in 2014 (P < .001). There was an increase in the BCS rate over time (P = .002); however, a higher proportion of the neoadjuvant group (55.5%) underwent mastectomy. Timing of chemotherapy influenced the type of reconstructive procedure carried out (P = .003). CONCLUSION: The number of patients with breast cancer being treated with NAC is increasing, which is influencing the increasing rate of BCS, though mastectomy is still central to the surgical management of those in receipt of NAC.

Neoadjuvant chemoradiation and breast reconstruction: the potential for improved outcomes in the treatment of breast cancer.

BACKGROUND: Immediate breast reconstruction (IBR) improves psychosocial and quality of life outcomes. Post-mastectomy radiation therapy is indicated for patients with a high risk of locoregional recurrence including locally advanced tumours (≥ 5 cm) or greater than or equal to four axillary nodes positive for breast cancer and can be a relative contraindication to IBR. Administration of radiation therapy pre-operatively, analogous to neoadjuvant chemotherapy, may reduce time to completion of treatment and facilitate better access to IBR. METHODS: This is a prospective pilot study in a tertiary referral breast cancer unit, comparing surgical, pathological response and oncological outcomes and time to completion of therapy for a prospective group of patients who received neoadjuvant radiotherapy with a cohort of age- and stage-matched patients requiring post-mastectomy (± reconstruction) radiation between 2010 and 2016. RESULTS: Sixteen patients with locally advanced breast cancer underwent neoadjuvant radiation and were age- and stage-matched to 32 patients who received post-mastectomy radiation therapy (PMRT) between 2010 and 2016. Neoadjuvant radiotherapy resulted in shorter time between diagnosis and treatment completion (245.6 ± 44.2 days in the neoadjuvant group, 291.2 ± 36.7 days in the adjuvant group, p = 0.001). A higher proportion of patients undergoing neoadjuvant chemoradiation therapy underwent breast reconstruction (14/16 patients in the neoadjuvant group, 15/32 patients in the adjuvant group, p = 0.007) without an increase in complication rate (p = 0.117). There was a trend towards improved pathological complete response and survival in the neoadjuvant group. CONCLUSION: This pilot study confirms that neoadjuvant chemoradiation is a feasible way of delivering breast cancer treatment and may facilitate improved access to IBR.

Hydrogels in adipose tissue engineering-Potential application in post-mastectomy breast regeneration.

Current methods of breast reconstruction are associated with significant shortcomings, including capsular contracture, infection, rupture, the need for reoperation in implant-based reconstruction, and donor site morbidity in autologous reconstruction. These limitations result in severe physical and psychological issues for breast cancer patients. Recently, research has moved into the field of adipose tissue engineering to overcome these limitations. A wide range of regenerative strategies has been devised utilising various scaffold designs and biomaterials. A scaffold capable of providing appropriate biochemical and biomechanical cues for adipogenesis is required. Hydrogels have been widely studied for their suitability for adipose tissue regeneration and are advantageous secondary to their ability to accurately imitate the native extracellular matrix. The aim of this review was to analyse the use of hydrogel scaffolds in the field of adipose tissue engineering.

Recent Advances and Future Directions in Postmastectomy Breast Reconstruction.

Postmastectomy breast reconstruction (PMBR) has evolved dramatically since it was first described by Vincent Czerny in 1895. The increasing numbers of mastectomy procedures and improved patient survival have placed an increasing emphasis on the aesthetic and psychosocial outcomes, prompting surgeons to develop more sophisticated methods to reconstruct the breast mound. Significant improvements have been made to existing implant and autologous methods of PMBR in recent decades in an effort to reduce donor site morbidity and complication rates and improve cosmesis. The limitations of contemporary methods of PMBR have directed research toward more novel techniques such as autologous fat grafting and adipose tissue engineering. The present review discusses recent advances in the evolution of contemporary approaches to breast reconstruction and the future directions of PMBR using adipose tissue engineering strategies.

The clinical utility of pre-operative neutrophil-to-lymphocyte ratio as a predictor of outcomes in patients undergoing elective laparoscopic cholecystectomy.

BACKGROUND: In recent years, there has been an increasing trend towards day-case surgery for patients undergoing laparoscopic cholecystectomy (LC). We investigated the predictive value that pre-operative neutrophil-to-lymphocyte ratio (PNLR) had on surgical outcomes. METHODS: A review of all patients who underwent LC during a 6-year period in a single institution was performed and PNLR recorded. A PNLR cutoff value of 3 was utilised. We compared operation time, length of stay (LOS), and conversion to open between those with PNLR less and greater than 3. RESULTS: A total of 567 patients underwent elective LC. Those with PNLR>3 had associated prolonged operation time (p < 0.005), prolonged LOS (p < 0.005), and higher rates of conversion to open surgery (p < 0.005). CONCLUSIONS: PNLR correlates with outcomes following LC. It is useful in delineating patients that have higher risk of conversion or prolonged length of hospital stay and is helpful in assessing suitability of day-case surgery.

Adipose-Derived Stem Cells in Novel Approaches to Breast Reconstruction: Their Suitability for Tissue Engineering and Oncological Safety.

Adipose-derived stem cells (ADSCs) are rapidly becoming the gold standard cell source for tissue engineering strategies and hold great potential for novel breast reconstruction strategies. However, their use in patients with breast cancer is controversial and their oncological safety, particularly in relation to local disease recurrence, has been questioned. In vitro, in vivo, and clinical studies using ADSCs report conflicting data on their suitability for adipose tissue regeneration in patients with cancer. This review aims to provide an overview of the potential role for ADSCs in breast reconstruction and to examine the evidence relating to the oncologic safety of their use in patients with breast cancer.