Evaluation of the Impact of Adaptive Progressive Supervised Resistance Training on Strength and Quality of Life in Patients with Breast Cancer During Chemotherapy: The VALESCO Study.

INTRODUCTION: Breast Cancer Patients (BCP) experience considerable side effects during and after treatment. Several studies have shown positive effects of exercise on therapy-related side-effects such as loss of muscle strength, loss of bone mineral density, lymphedema and several elements of quality of life (QoL). Resistance exercise has proven effective and beneficial for BCP; however optimal individual training parameters remain to be determined. METHODS: The aim of our study was to implement an adaptive, progressive, supervised resistance protocol for breast cancer patients during chemotherapy, improving muscle strength, physical condition, and overall QoL while reducing therapy-induced side-effects. 40 patients receiving adjuvant chemotherapy were included six to twelve weeks post-OP. 20 patients underwent high intensity resistance-training twice a week for twelve weeks, and the control group received usual care. RESULTS: Strength parameters improved significantly in the intervention group and in different scales of QoL. We documented a cyclic performance level underlining the importance of adaptive training and training control in further trials.

Sonographic Assessment of Breast Implants Using Strain Elastography and Shear Wave Elastography in an Animal Model.

BACKGROUND/AIM: To date, magnetic resonance imaging (MRI) remains the gold standard for diagnosing breast implant rupture. As MRI is an expensive procedure with limited availability, the improvement of sonographic assessment is desirable. A potentially useful tool in this regard is elastography. To evaluate the diagnostic benefits of strain elastography and shear wave elastography under standardized conditions we developed an animal model. MATERIALS AND METHODS: An animal model was created by preparing an implant site in a chicken breast, imitating tissue layers covering a breast implant after mastectomy. Different broken and intact implants were inserted. Thereby, measurements were performed using strain elastography and shear wave elastography. For strain elastography, the resulting images were investigated on repeated patterns. The data generated by shear wave elastography were analyzed for significant differences between the ruptured and intact implants. RESULTS: The animal model using chicken breast generated realistic images and measurements comparable to those of a human breast. Hence, ruptured and intact implants could be compared under standardized conditions. Statistical analysis showed no significant difference between intact and ruptured implants with respect to the data generated by shear wave elastography. Qualitative analysis using strain wave elastography showed different patterns between intact and ruptured implants in the animal model. Intact implants showed a characteristic sonographic image of three layers in certain levels. CONCLUSION: Shear wave elastography does not seem to produce reliable data for the evaluation of breast implants, whereas qualitative analysis using strain elastography might be a useful tool to improve diagnostic accuracy.

Assignment of the biological value of solid breast masses based on quantitative evaluations of spectral CT examinations using electron density mapping, Zeffective mapping and iodine mapping.

OBJECTIVE: We aimed to asses, in a clinical setting, whether the newly available quantitative evaluation of electron density (ED) in spectral CT examinations of the breast provide information on the biological identity of solid breast masses and whether ED maps yield added value to the diagnostic information of iodine maps and Zeff maps calculated from the same CT image datasets. METHODS: All patients at the University Breast Cancer Center who underwent a clinically indicated Dual Layer Computed Tomography (DLCT) examination for staging of invasive breast cancer from 2018 to 2020 were prospectively included. Iodine concentration maps, Zeff maps and ED maps were automatically reconstructed from the DLCT datasets. Region of interest (ROI) based evaluations in the breast target lesions and in the aorta were performed semi-automatically in identical anatomical positions using dedicated evaluation software. Case-by-case evaluations were carried independently by 2 of 4 radiologists for each examination, respectively. Statistical analysis derived from the ROIs was done by calculating ROC/AUC curves and Youden indices. RESULTS: The evaluations comprised 166 DLCT examinations. In the ED maps the measurements in the breast target lesions yielded Youden cutpoints of 104.0% (reader 1) and 103.8% (reader 2) resulting in AUCs of 0.63 and 0.67 at the empirical cutpoints. The variables "Zeff" and "iodine content" derived from the target lesions showed superior diagnostical results, with a Youden cutpoint of 8.0 mg/ml in the iodine maps and cutpoints of 1.1/1.2 in the Zeff maps the AUCs ranging from 0.84 to 0.85 (p = 0.023 to <0.000). The computational combination of Zeff and ED measurements in the target lesions yielded a slight AUC increase (readers 1: 0.85-0.87; readers 2: 0.84-0.94). The ratios of the measured values in the target lesions normalized to the values measured in the aorta showed comparable results. The AUCs of ED derived from the cutpoints showed inferior results to those derived from the Zeff maps and iodine maps (ED: 0.64 and 0.66 for reader 1 and 2; Zeff: 0.86 for both readers; iodine content: 0.89 and 0.86 for reader 1 and 2, respectively). The computational combination of the ED results and the Zeff measurements did not lead to a clinically relevant diagnostic gain with AUCs ranging from 0.86 to 0.88. CONCLUSIONS: Quantitative assessments of Zeff, iodine content and ED all targeting the physical and chemical aspects of iodine uptake in solid breast masses confirmed diagnostically robust cutpoints for the differentiation of benign and malignant findings (Zeff < 7.7, iodine content of <0.8 mg/ml). The evaluations of the ED did not indicate any added diagnostic value beyond the quantitative assessments of Zeff and iodine content. Further research is warranted to develop suitable clinical indications for the use of ED maps.

Minimally Invasive Breast Biopsy After Neoadjuvant Systemic Treatment to Identify Breast Cancer Patients with Residual Disease for Extended Neoadjuvant Treatment: A New Concept.

BACKGROUND: Breast cancer patients with residual disease after neoadjuvant systemic treatment (NAST) have a worse prognosis compared with those achieving a pathologic complete response (pCR). Earlier identification of these patients might allow timely, extended neoadjuvant treatment strategies. We explored the feasibility of a vacuum-assisted biopsy (VAB) after NAST to identify patients with residual disease (ypT+ or ypN+) prior to surgery. METHODS: We used data from a multicenter trial, collected at 21 study sites (NCT02948764). The trial included women with cT1-3, cN0/+ breast cancer undergoing routine post-neoadjuvant imaging (ultrasound, MRI, mammography) and VAB prior to surgery. We compared the findings of VAB and routine imaging with the histopathologic evaluation of the surgical specimen. RESULTS: Of 398 patients, 34 patients with missing ypN status and 127 patients with luminal tumors were excluded. Among the remaining 237 patients, tumor cells in the VAB indicated a surgical non-pCR in all patients (73/73, positive predictive value [PPV] 100%), whereas PPV of routine imaging after NAST was 56.0% (75/134). Sensitivity of the VAB was 72.3% (73/101), and 74.3% for sensitivity of imaging (75/101). CONCLUSION: Residual cancer found in a VAB specimen after NAST always corresponds to non-pCR. Residual cancer assumed on routine imaging after NAST corresponds to actual residual cancer in about half of patients. Response assessment by VAB is not safe for the exclusion of residual cancer. Response assessment by biopsies after NAST may allow studying the new concept of extended neoadjuvant treatment for patients with residual disease in future trials.

A Retrospective Multicenter Analysis of Diagon/Gel® 4Two Implant in 209 Cases of Reconstructive Breast Surgery.

BACKGROUND/AIM: Breast cancer was the most common cancer in women in 2020. Breast reconstruction is an elementary component of modern breast surgery. This is especially important after oncological treatments. This is a retrospective multicenter study comparing Diagon\Gel® 4Two implants with different implants chosen by the treating surgeon. Diagon\Gel® 4Two (Polytech Health & Aesthetics, Germany) are anatomical silicone implants. PATIENTS AND METHODS: A total of 209 patients underwent surgery. All patients were treated in the period from 2001 to 2019. All procedures were subcutaneous mastectomies. The surgical techniques used were either skin-sparing mastectomies or nipple-sparing mastectomies. Surgery was performed with Diagon/Gel® 4Two implant or treatment of choice implant by the treating physician. Endpoints were major and minor complication rates. The average follow-up time was 5 years. In total, 110 subjects were asked about their satisfaction with the treatment. RESULTS: A total of 155 procedures were performed in the Diagon/Gel® 4Two implant group. One hundred and sixty procedures were done in the comparison group. Concerning either minor or major complications, there were no significant differences between both groups. The postoperative patient survey showed high satisfaction scores for both. There was significantly higher patient satisfaction among the study participants in the Diagon/Gel® 4Two implant group compared to the comparison group (p<0.01). CONCLUSION: The Diagon/Gel® 4Two implants are safe alternatives in direct comparison to previously used breast implants. Our study even demonstrated a slight superiority concerning patient satisfaction. Based on this study, further implants can be compared concerning both the direct perioperative complication rate and patient satisfaction.

Intermodal correlation of quantitative CT-data and MRI-biomarkers derived from synchronous spectral CT-maps and breast MRI-examinations with molecular biomarkers in invasive ductal breast carcinomas.

OBJECTIVE: To asses the correlation of data derived from dual-layer (DL)-CT material-maps and breast MRI data with molecular biomarkers in invasive breast carcinomas. METHODS: All patients at the University Breast Cancer Center who underwent a clinically indicated DLCT-scan and a breast MRI for staging of invasive ductal breast cancer from 2016 to 2020 were prospectively included. Iodine concentration-maps, and Zeffective-maps were reconstructed from the CT-datasets. T1w- and T2w-signal intensities, ADC and the clustered shapes of the dynamic-curves (washout, plateau, persistent) were derived from the MRI-datasets. ROI-based evaluations of the cancers and the reference "musculature" were performed semi-automatically in identical anatomical positions using dedicated evaluation software. Statistical analysis was essentially descriptive using Spearmans rank correlation and (multivariable) partial correlation. RESULTS: The signal intensities measured in the 3rd phase of the contrast dynamics correlated at an intermediate level of significance with the iodine content and the Zeffective-values derived from the breast target lesions (Spearmans rank correlation-coefficient r = 0.237/0.236, p = 0.002/0.003). The bivariate and the multivariate analyses displayed correlations of an intermediate significance level of the iodine content and the Zeff-values measured in the breast target lesions with immunhistochemical subtyping (r = 0.211-0.243, p = 0.002-0.009, respectively). The Zeff-values showed the strongest correlations when normalized to the values measured in the musculature and in the aorta (r = -0.237 to -0.305, r=<0.001-0.003). The MRI-assessments showed correlations of intermediate to high significance and low to intermediate significance between the ratios of the T2w-signal intensities and the trends of the dynamic curves measured in the breast target lesions and in musculature and immunohistochemical cancer subtyping, respectively (T2w: r = 0.232-0.249, p = 0.003/0.002; dynamics: r = -0.322/-0.245, p=<0.001/0.002). The ratios of the clustered trends of the dynamic curves measured in the breast target lesions and in musculature correlated with tumor grading on intermediate significance level (r = -0.213 and -0.194, p = 0.007/0.016) and with Ki-67 on a low significance level (bivariate analysis: r = -0.160, p = 0.040). There was only a weak correlation between the ADC-values measured in the breast target lesions and HER2-expression (bivariate ansalysis: r = 0.191, p = 0.030). CONCLUSIONS: Our preliminary results indicate that evaluation of perfusion based DLCT-data and MRI-biomarkers show correlations with the immunhistochemical subtyping of invasive ductal breast carcinomas. Further clinical research is warranted in order to validate the value of the results and define clinical situations in which the use of the described DLCT-biomaker and MRI biomarkers may be helpful in clinical patient care.

Ex Vivo Infection of Human Skin Models with Herpes Simplex Virus 1: Accessibility of the Receptor Nectin-1 during Formation or Impairment of Epidermal Barriers Is Restricted by Tight Junctions.

Herpes simplex virus 1 (HSV-1) must overcome epidermal barriers to reach its receptors on keratinocytes and initiate infection in human skin. The cell-adhesion molecule nectin-1, which is expressed in human epidermis, acts as an efficient receptor for HSV-1 but is not within reach of the virus upon exposure of human skin under nonpathological conditions. Atopic dermatitis skin, however, can provide an entry portal for HSV-1 emphasizing the role of impaired barrier functions. Here, we explored how epidermal barriers impact HSV-1 invasion in human epidermis and influence the accessibility of nectin-1 for the virus. Using human epidermal equivalents, we observed a correlation of the number of infected cells with tight-junction formation, suggesting that mature tight junctions prior to formation of the stratum corneum prevent viral access to nectin-1. Consequently, impaired epidermal barriers driven by Th2-inflammatory cytokines interleukin 4 (IL-4) and IL-13 as well as the genetic predisposition of nonlesional atopic dermatitis keratinocytes correlated with enhanced infection supporting the impact of functional tight junctions for preventing infection in human epidermis. Comparable to E-cadherin, nectin-1 was distributed throughout the epidermal layers and localized just underneath the tight-junctions. While nectin-1 was evenly distributed on primary human keratinocytes in culture, the receptor was enriched at lateral surfaces of basal and suprabasal cells during differentiation. Nectin-1 showed no major redistribution in the thickened atopic dermatitis and IL-4/IL-13-treated human epidermis in which HSV-1 can invade. However, nectin-1 localization toward tight junction components changed, suggesting that defective tight-junction barriers make nectin-1 accessible for HSV-1 which enables facilitated viral penetration. IMPORTANCE Herpes simplex virus 1 (HSV-1) is a widely distributed human pathogen which productively infects epithelia. The open question is which barriers of the highly protected epithelia must the virus overcome to reach its receptor nectin-1. Here, we used human epidermal equivalents to understand how physical barrier formation and nectin-1 distribution contribute to successful viral invasion. Inflammation-induced barrier defects led to facilitated viral penetration strengthening the role of functional tight-junctions in hindering viral access to nectin-1 that is localized just underneath tight junctions and distributed throughout all layers. We also found nectin-1 ubiquitously localized in the epidermis of atopic dermatitis and IL-4/IL-13-treated human skin implying that impaired tight-junctions in combination with a defective cornified layer allow the accessibility of nectin-1 to HSV-1. Our results support that successful invasion of HSV-1 in human skin relies on defective epidermal barriers, which not only include a dysfunctional cornified layer but also depend on impaired tight junctions.

De-Escalated Neoadjuvant Trastuzumab-Emtansine With or Without Endocrine Therapy Versus Trastuzumab With Endocrine Therapy in HR+/HER2+ Early Breast Cancer: 5-Year Survival in the WSG-ADAPT-TP Trial.

PURPOSE: Neoadjuvant chemotherapy is standard of care in human epidermal growth factor receptor 2-positive (HER2+) early breast cancer (EBC), irrespective of the hormone receptor status. Trastuzumab-emtansine (T-DM1), antibody-drug conjugate, is highly effective in HER2+ EBC; however, no survival data are available for de-escalated antibody-drug conjugate-based neoadjuvant therapy without conventional chemotherapy. PATIENTS AND METHODS: In the WSG-ADAPT-TP (ClinicalTrials.gov identifier: NCT01779206) phase II trial, 375 centrally reviewed patients with hormone receptor-positive (HR+)/HER2+ EBC (clinical stage I-III) were randomly assigned to 12 weeks of T-DM1 with or without endocrine therapy (ET) or trastuzumab + ET once every 3 weeks (ratio 1:1:1). Adjuvant chemotherapy (ACT) omission was allowed in patients with pathologic complete response (pCR). In this study, we report the secondary survival end points and biomarker analysis. Patients who received at least one dose of study treatment were analyzed. Survival was analyzed using the Kaplan-Meier method, two-sided log-rank statistics, and Cox regression models stratified for nodal and menopausal status. P values < .05 were considered statistically significant. RESULTS: T-DM1, T-DM1 + ET, and trastuzumab + ET induced similar 5-year invasive disease-free survival (iDFS; 88.9%, 85.3%, 84.6%; Plog-rank = .608) and overall survival rates (97.2%, 96.4%, 96.3%; Plog-rank = .534). Patients with pCR versus non-pCR had improved 5-year iDFS rates (92.7% v 82.7%; hazard ratio, 0.40 [95% CI, 0.18 to 0.85]). Among the 117 patients with pCR, 41 did not receive ACT; 5-year iDFS rates were similar in those with (93.0% [95% CI, 84.0 to 97.0]) and without ACT (92.1% [95% CI, 77.5 to 97.4]; Plog-rank = .848). Translational research revealed that tumors with PIK3CA wild type, high immune marker expression, and luminal-A tumors (by PAM50) had an excellent prognosis with de-escalated anti-HER2 therapy. CONCLUSION: The WSG-ADAPT-TP trial demonstrated that pCR after 12 weeks of chemotherapy-free de-escalated neoadjuvant therapy was associated with excellent survival in HR+/HER2+ EBC without further ACT. Despite higher pCR rates for T-DM1 ± ET versus trastuzumab + ET, all trial arms had similar outcomes because of mandatory standard chemotherapy after non-pCR. WSG-ADAPT-TP demonstrated that such de-escalation trials in HER2+ EBC are feasible and safe for patients. Patient selection on the basis of biomarkers or molecular subtypes may increase the efficacy of systemic chemotherapy-free HER2-targeted approaches.

Trophoblast Cell Surface Antigen 2 (TROP2) as a Predictive Bio-Marker for the Therapeutic Efficacy of Sacituzumab Govitecan in Adenocarcinoma of the Esophagus.

INTRODUCTION: The Trophoblast cell surface antigen 2 (TROP2) is expressed in many carcinomas and may represent a target for treatment. Sacituzumab govitecan (SG) is a TROP2-directed antibody-drug conjugate (ADC). Nearly nothing is known about the biological effectiveness of SG in esophageal adenocarcinoma (EAC). MATERIAL AND METHODS: We determined the TROP2 expression in nearly 600 human EAC. In addition, we used the EAC cell lines (ESO-26, OACM5.1C, and FLO-1) and a xenograft mouse model to investigate this relationship. RESULTS: Of 598 human EACs analyzed, 88% showed varying degrees of TROP2 positivity. High TROP2 positive ESO-26 and low TROP2 positive OACM5.1C showed high sensitivity to SG in contrast to negative FLO-1. In vivo, the ESO-26 tumor shows a significantly better response to SG than the TROP2-negative FLO-1 tumor. ESO-26 vital tumor cells show similar TROP2 expression on all carcinoma cells as before therapy initiation, FLO-1 is persistently negative. DISCUSSION: Our data suggest that sacituzumab govitecan is a new therapy option in esophageal adenocarcinoma and the TROP2 expression in irinotecan-naïve EAC correlates with the extent of treatment response by sacituzumab govitecan. TROP2 is emerging as a predictive biomarker in completely TROP2-negative tumors. This should be considered in future clinical trials.

Correlation of CT-data derived from multiparametric dual-layer CT-maps with immunohistochemical biomarkers in invasive breast carcinomas.

OBJECTIVE: To examine the correlation of quantitative measurements from material decomposition maps calculated from dual-layer CT (DLCT)-image datasets with immunohistochemical biomarkers of invasive breast carcinomas. MATERIAL AND METHODS: All patients at the University Breast Cancer Center who underwent a clinically indicated dual-layer CT-scan for staging of invasive ductal breast carcinoma from 01/2016 to 07/2020 were prospectively included. Iodine concentration maps and maps of the effective atomic numbers (Zeffective) were reconstructed from the image datasets. ROI-based evaluations of the index tumors and predefined references tissues for normalization were performed semi-automatically in identical anatomical positions using dedicated evaluation software. Statistical analysis was essentially descriptive using Spearmans rank correlation and (multivariable) partial correlation. RESULTS: Bivariate showed statistically significant correlations of iodine contents (r = -0.154/-0.202/0.180, p = 0.039/0.006/0.015), and Zeffective-values (r = -0.158/-0.199/0.179, p = 0.034/0.007/0.016) for all 184 carcinomas and the subgroup of 168 invasive ductal carcinomas. The results were confirmed by multivariate analyses with "age", "diameter" and "ACR-grade" as possible confounders. Normalization of the measured target values with those in the aorta confirmed significant correlations of iodine content and Zeffective compared to Estrogen (r = 0.174, p = 0.019), Progesteron (r = 0.168/0.177, p = 0.024/0.017), and HER2 receptor expression (r = -0.222/-0.184, p = 0.003/0.013). All CT-parameters showed significant correlations with immunohistochemical subtyping (r = 0.191/0.192, p = 0.010). CONCLUSIONS: Our preliminary results indicate that iodine content and Zeffective-values derived from DLCT-examinations correlate with hormone receptor expression in invasive breast carcinomas. Assignments to benign entities already seam feasible in clinical routine CT-diagnostics. After further investigations iodine content and Zeffective may be translated as diagnostical and prognostical biomarkers into clinical routine in the long term.

Evaluation of Real-world Data for Breast-MRI BI-RADS IV Lesions.

BACKGROUND/AIM: Magnetic resonance imaging (MRI) is an important diagnostic tool in the detection of breast cancer. The Breast Center of the municipal Hospital Holweide, Cologne, annually cares for and treats patients with changes in the breast. A special problem is posed by Breast Imaging-Reporting and Data System (BI-RADS) 4 lesions. If a BI-RADS 4 finding is present, is a vacuum biopsy indicated in every case or, if there is already an indication for surgery due to other findings, can the corresponding finding be removed openly without histological clarification? We require real world data regarding the actual in-center likelihood of a BIRADS 4 lesion to be DCIS (Ductal carcinoma in situ) or invasive disease. PATIENTS AND METHODS: This is a retrospective study of 1,641 patients who received MRI examination in the radiological department of the municipal hospital Holweide in 2012 and 2013. Each BI-RADS 4 finding (or higher) classified by MRI was compared with the final histological result. RESULTS: 347 MRIs showed BI-RADS 4 findings or higher and 280 (80.7%) cases showed benign histology. In 67 (19.3%) cases, histology showed DCIS or invasive carcinoma. CONCLUSION: BI-RADS 4 lesions have a low probability of malignancy based on real-world data from this center. If there is already an indication for surgery due to other lesions, the patient can also be offered a simultaneous open biopsy in the context of the already initiated surgical treatment. Each center should know the sensitivity and specificity of the MRI imaging performed and counsel patients based on that.

Herpes Simplex Virus 1 Can Bypass Impaired Epidermal Barriers upon Ex Vivo Infection of Skin from Atopic Dermatitis Patients.

To infect its human host, herpes simplex virus 1 (HSV-1) must overcome the protective barriers of skin and mucosa. Here, we addressed whether pathological skin conditions can facilitate viral entry via the skin surface and used ex vivo infection studies to explore viral invasion in atopic dermatitis (AD) skin characterized by disturbed barrier functions. Our focus was on the visualization of the onset of infection in single cells to determine the primary entry portals in the epidermis. After ex vivo infection of lesional AD skin, we observed infected cells in suprabasal layers indicating successful invasion in the epidermis via the skin surface which was never detected in control skin where only sample edges allowed viral access. The redistribution of filaggrin, loricrin, and tight-junction components in the lesional skin samples suggested multiple defective mechanical barriers. To dissect the parameters that contribute to HSV-1 invasion, we induced an AD-like phenotype by adding the Th2 cytokines interleukin 4 (IL-4) and IL-13 to healthy human skin samples. Strikingly, we detected infected cells in the epidermis, implying that the IL-4/IL-13-driven inflammation is sufficient to induce modifications allowing HSV-1 to penetrate the skin surface. In summary, not only did lesional AD skin facilitate HSV-1 penetration but IL-4/IL-13 responses alone allowed virus invasion. Our results suggest that the defective epidermal barriers of AD skin and the inflammation-induced altered barriers in healthy skin can make receptors accessible for HSV-1. IMPORTANCE Herpes simplex virus 1 (HSV-1) can target skin to establish primary infection in the epithelium. While the human skin provides effective barriers against viral invasion under healthy conditions, a prominent example of successful invasion is the disseminated HSV-1 infection in the skin of atopic dermatitis (AD) patients. AD is characterized by impaired epidermal barrier functions, chronic inflammation, and dysbiosis of skin microbiota. We addressed the initial invasion process of HSV-1 in atopic dermatitis skin to understand whether the physical barrier functions are sufficiently disturbed to allow the virus to invade skin and reach its receptors on skin cells. Our results demonstrate that HSV-1 can indeed penetrate and initiate infection in atopic dermatitis skin. Since treatment of skin with IL-4 and IL-13 already resulted in successful invasion, we assume that inflammation-induced barrier defects play an important role for the facilitated access of HSV-1 to its target cells.

Endocrine Therapy Response and 21-Gene Expression Assay for Therapy Guidance in HR+/HER2- Early Breast Cancer.

PURPOSE: To our knowledge, WSG-ADAPT-HR+/HER2- (ClinicalTrials.gov identifier: NCT01779206; n = 5,625 registered) is the first trial combining the 21-gene expression assay (recurrence score [RS]) and response to 3-week preoperative endocrine therapy (ET) to guide systemic therapy in early breast cancer. MATERIALS AND METHODS: Baseline and postendocrine Ki67 (Ki67post) were evaluated centrally. In the endocrine trial, all patients received exclusively ET: patients with pathologic regional lymph node status (pN) 0-1 (ie, 0-3 involved lymph nodes) entered control arm if RS ≤ 11 and experimental arm if RS12-25 with ET response (Ki67post ≤ 10%). All other patients (including N0-1 RS12-25 without ET response) received dose-dense chemotherapy (CT) followed by ET in the CT trial. Primary end point of the endocrine trial was noninferiority of 5-year invasive disease-free survival (5y-iDFS) in experimental (v control) arm; secondary end points included distant DFS, overall survival, and translational research. RESULTS: Intention-to-treat population comprised 2,290 patients (n = 1,422 experimental v n = 868 control): 26.3% versus 34.6% premenopausal and 27.4% versus 24.0% pN1. One-sided 95% lower confidence limit of the 5y-iDFS difference was -3.3%, establishing prespecified noninferiority (P = .05). 5y-iDFS was 92.6% (95% CI, 90.8 to 94.0) in experimental versus 93.9% (95% CI, 91.8 to 95.4) in control arm; 5-year distant DFS was 95.6% versus 96.3%, and 5-year overall survival 97.3% versus 98.0%, respectively. Differences were similar in age and nodal subgroups. In N0-1 RS12-25, outcome of ET responders (ET alone) was comparable with that of ET nonresponders (CT) for age > 50 years and superior for age ≤ 50 years. ET response was more likely with aromatase inhibitors (mostly postmenopausal) than with tamoxifen (mostly premenopausal): 78.1% versus 41.1% (P < .001). ET response was 78.8% in RS0-11, 62.2% in RS12-25, and 32.7% in RS > 25 (n = 4,203, P < .001). CONCLUSION: WSG-ADAPT-HR+/HER2- demonstrates that guiding systemic treatment by both RS and ET response is feasible in clinical routine and spares CT in pre- and postmenopausal patients with ≤ 3 involved lymph nodes.

Platelet-rich plasma (PRP) in oncological patients: long-term oncological outcome analysis of the treatment of subcutaneous venous access device scars in 89 breast cancer patients.

PURPOSE: Platelet-rich plasma (PRP) is widely used product, and meta-analyses showed this product to be beneficial when applied to a wound area. This study group has already demonstrated increased patient satisfaction and lower complication rates in breast cancer patients who received PRP after removal of their subcutaneous venous access device. This work is a follow-up analysis focusing on oncologic safety. Currently, there is no long-term data on the use of PRP products in cancer patients available yet. METHODS: Between the years 2012-2016, venous access device removal was supported with the application of Arthrex ACP® (Autologous Conditioned Plasma)-a PRP product to improve the wound-healing process. All surgeries were performed in the breast cancer center of the municipal hospital of Cologne, Holweide, Germany. 35 patients received an application of Arthrex ACP® after port removal compared to the control group of 54 patients. Endpoints were local recurrence-free, distant recurrence-free as well as overall survival. RESULTS: Median follow-up was 45 months. No (0) adverse events were shown for cancer recurrence within the subcutaneous venous access device scar area. Thus, there seems to be no local oncogenic potential of the PRP product. All other endpoints as well as any-cause death numerically favor PRP use. CONCLUSION: PRP products such as Arthrex ACP® seem to be oncological inert when applied after removal of subcutaneous access devices. This is the first study providing long-term data about overall survival, distant recurrence-free and local recurrence-free survival after applying PRP in high-risk cancer patients.

Improving Breast Conserving Surgery Using the Faxitron® OR Specimen Radiography System - A Complication Analysis, Cost Evaluation and Literature Review.

BACKGROUND/AIM: The combination of pre-surgical clip placement and hook-wire guided surgery is considered the gold standard for adequately locating non-palpable lesions during breast conserving surgery. After surgical removal of the segment, radiography is required to confirm clip removal, increasing surgical time, post-surgical complication rates, and cost. PATIENTS AND METHODS: We performed a retrospective analysis, using the Faxitron® in-theater specimen radiography system, of the following primary endpoints: surgical time and complication rates. The secondary endpoints were cost effectiveness and clip-location rates. The Control cohort included breast conserving surgery patients prior to May 2019 (n=150) and the Validation cohort included breast conserving surgery patients after May 2019 (n=53). RESULTS: The analysis showed an improvement in surgical time when using the Faxitron® system, which is directly linked to a benefit in cost effectiveness. A numerical benefit in complication rates was also shown. A subgroup analysis showed a significant advantage in surgical time for breast conserving surgery plus sentinel node biopsy and open breast biopsies. CONCLUSION: Use of the Faxitron® system significantly reduces surgical time, which increases cost efficiency while maintaining a low complication rate.

Intelligent Vacuum-Assisted Biopsy to Identify Breast Cancer Patients With Pathologic Complete Response (ypT0 and ypN0) After Neoadjuvant Systemic Treatment for Omission of Breast and Axillary Surgery.

PURPOSE: Neoadjuvant systemic treatment (NST) elicits a pathologic complete response in 40%-70% of women with breast cancer. These patients may not need surgery as all local tumor has already been eradicated by NST. However, nonsurgical approaches, including imaging or vacuum-assisted biopsy (VAB), were not able to accurately identify patients without residual cancer in the breast or axilla. We evaluated the feasibility of a machine learning algorithm (intelligent VAB) to identify exceptional responders to NST. METHODS: We trained, tested, and validated a machine learning algorithm using patient, imaging, tumor, and VAB variables to detect residual cancer after NST (ypT+ or in situ or ypN+) before surgery. We used data from 318 women with cT1-3, cN0 or +, human epidermal growth factor receptor 2-positive, triple-negative, or high-proliferative Luminal B-like breast cancer who underwent VAB before surgery (ClinicalTrials.gov identifier: NCT02948764, RESPONDER trial). We used 10-fold cross-validation to train and test the algorithm, which was then externally validated using data of an independent trial (ClinicalTrials.gov identifier: NCT02575612). We compared findings with the histopathologic evaluation of the surgical specimen. We considered false-negative rate (FNR) and specificity to be the main outcomes. RESULTS: In the development set (n = 318) and external validation set (n = 45), the intelligent VAB showed an FNR of 0.0%-5.2%, a specificity of 37.5%-40.0%, and an area under the receiver operating characteristic curve of 0.91-0.92 to detect residual cancer (ypT+ or in situ or ypN+) after NST. Spiegelhalter's Z confirmed a well-calibrated model (z score -0.746, P = .228). FNR of the intelligent VAB was lower compared with imaging after NST, VAB alone, or combinations of both. CONCLUSION: An intelligent VAB algorithm can reliably exclude residual cancer after NST. The omission of breast and axillary surgery for these exceptional responders may be evaluated in future trials.

Tacks vs. sutures: a biomechanical analysis of sacral bony fixation methods for laparoscopic apical fixations in the porcine model.

PURPOSE: There is a novel surgical procedure, called cervicosacropexy (CESA) and vaginosacropexy (VASA) to treat pelvic organ prolapse and a concomitant urgency and mixed urinary incontinence. As there is little experience with the tapes so far and literature is scanty, the aim of this study was to investigate biomechanical properties for the fixation of the PVDF-tapes with three different fixation methods in context of apical fixations. METHODS: Evaluation was performed on porcine, fresh cadaver sacral spines. A total of 40 trials, divided into 4 subgroups, was performed on the anterior longitudinal ligament. Recorded biomechanical properties were displacement at failure, maximum load and stiffness in terms of the primary endpoints. The failure mode was a secondary endpoint. Group 4 was a reference group to compare single sutures on porcine tissue with those on human tissue. Biomechanical parameters for single sutures on the human anterior longitudinal ligament were evaluated in a previous work by Hachenberg et al. RESULTS: The maximum load for group 1 (two single sutures) was 65 ± 12 N, for group 2 (three titanium tacks arranged in a row) it was 25 ± 10 N and for group 3 (three titanium tacks arranged in a triangle) it was 38 ± 12 N. There was a significant difference between all three groups. The most common failure mode was a "mesh failure" in 9/10 trials for groups 1-3. CONCLUSION: The PVDF-tape fixation with two single sutures endures 2.6 times more load than titanium tacks arranged in a row and 1.7 times more load than titanium tacks arranged in a triangle. The presacral fixation with titanium tacks reduced surgical time compared to the fixation with sutures, nevertheless sutures represent the significantly stronger and cheaper fixation method.

Impact of demographic and perioperative risk factors on complication rates in skin-sparing/nipple-sparing mastectomy with implant-based reconstruction using titanized polypropylene mesh (TiLOOP® Bra).

BACKGROUND: Skin/nipple-sparing mastectomies (SSM/NSSM) have been reported to have acceptable complication rates and good aesthetic outcomes with high patient satisfaction. However, in this relatively young and rapidly expanding field of reconstructive plastic surgery, differences in perioperative management are noted between breast centers. Prospective studies of complication rates using a titanized polypropylene mesh (TiLOOP® Bra) are currently lacking. METHODS: A prospective subgroup analysis was performed based on the data set of the prospective, single-arm, multicenter observational study (PRO-BRA). Early complication rates after skin/nipple-sparing mastectomy with implant-based immediate or secondary reconstruction using a titanized polypropylene mesh (TiLOOP® Bra) subpectorally were investigated in relation to demographic factors, as well as intra-and postoperative management. The subgroup consists of 258 patients. Complications were categorised into necrosis, infection, postoperative bleeding or hematoma, seroma, wound healing delays and R1-situations. RESULTS: Early complication rates of SSM/NSSM using titanium-based meshes are comparable to complication-rates using ADM's. Logistic regression shows significantly higher risk for wound healing delays, necrosis and seroma with increasing BMI, abladat- and implant-weight (OR 1,17 -1,66, p-value < 0,001). Smokers have significantly higher necrosis rates (20.7%) compared to non-smokers (5.5%) (p-value = 0.002). Discharge with drainage results in a trend toward higher rates of wound healing complications. CONCLUSION: The use of TiLOOP® Bra meshes was shown to have acceptable complication rates. Complication rates depend on certain demographic and intraoperative risk factors and should be considered in indications and information of patients.

A biomechanical analysis of different meshes for reconstructions of the pelvic floor in the porcine model.

PURPOSE: Many different surgical approaches have been established for the repair of a pelvic organ prolapse. Especially in laparoscopic surgery, it is important to generate easy surgical techniques with similar stability. This study shall simplify the choice of mesh by evaluating three polypropylene meshes regarding their biomechanical properties. METHODS: Biomechanical testing was performed in the porcine model. The meshes are fixated on porcine fresh cadaver cervices after subtotal hysterectomy. The apical part of the mesh is fixated with parallel screw clamps at the testing frame. Forty-one trials were performed overall, subdivided into four subgroups. The groups differ in mesh type and fixation method. Maximum load, displacement at failure and stiffness parameters were evaluated with an Instron 5565® test frame. RESULTS: SERATEX® E11 PA (E11) showed the highest values for maximum load (199 ± 29N), failure displacement (71 ± 12 mm) and stiffness (3.93 ± 0.59 N/mm). There was no significant difference in all three evaluated parameters between SERATEX® B3 PA (B3) and SERATEX® SlimSling® with bilateral fixation (SSB). SERATEX® SlimSling® with unilateral fixation (SSU) had the lowest stiffness (0.91 ± 0.19 N/mm) and maximum load (30 ± 2 N) but no significant difference in displacement at failure. CONCLUSION: All meshes achieved a good tensile strength, but the results of maximum load show that the E11 is superior to the other meshes. Through a bilateral fixation of SERATEX® SlimSling®, a simple operating method is generated without a loss of stability.