Resection Ratios and Tumor Eccentricity in Breast-Conserving Surgery Specimens for Surgical Accuracy Assessment

This study aims to evaluate several defined specimen parameters that would allow to determine the surgical accuracy of breast-conserving surgeries (BCS) in a representative population of patients. These specimen parameters could be used to compare surgical accuracy when using novel technologies for intra-operative BCS guidance in the future. Different specimen parameters were determined among 100 BCS patients, including the ratio of specimen volume to tumor volume (resection ratio) with different optimal margin widths (0 mm, 1 mm, 2 mm, and 10 mm). Furthermore, the tumor eccentricity [maximum tumor-margin distance − minimum tumor-margin distance] and the relative tumor eccentricity [tumor eccentricity ÷ pathological tumor diameter] were determined. Different patient subgroups were compared using Wilcoxon rank sum tests. When using a surgical margin width of 0 mm, 1 mm, 2 mm, and 10 mm, on average, 19.16 (IQR 44.36), 9.94 (IQR 18.09), 6.06 (IQR 9.69) and 1.35 (IQR 1.78) times the ideal resection volume was excised, respectively. The median tumor eccentricity among the entire patient population was 11.29 mm (SD = 3.99) and the median relative tumor eccentricity was 0.66 (SD = 2.22). Resection ratios based on different optimal margin widths (0 mm, 1 mm, 2 mm, and 10 mm) and the (relative) tumor eccentricity could be valuable outcome measures to evaluate the surgical accuracy of novel technologies for intra-operative BCS guidance.</p

From Multiple Quality Indicators of Breast Cancer Care Toward Hospital Variation of a Summary Measure

Objectives: To improve quality in breast cancer care, large numbers of quality indicators are collected per hospital, but benchmarking remains complex. We aimed to assess the validity of indicators, develop a textbook outcome summary measure, and compare case-mix adjusted hospital performance. Methods: From a nationwide population-based registry, all 79 690 nonmetastatic breast cancer patients surgically treated between 2011 and 2016 in 91 hospitals in The Netherlands were included. Twenty-one indicators were calculated and their construct validity tested by Spearman's rho. Between-hospital variation was expressed by interquartile range (IQR), and all valid indicators were included in the summary measure. Standardized scores (observed/expected based on case mix) were calculated as above (>100) or below (<100) expected. The textbook outcome was presented as a continuous and all-or-none score. Results: The size of between-hospital variation varied between indicators. Sixteen (76%) of 21 quality indicators showed construct validity, and 13 were included in the summary measure after excluding redundant indicators that showed collinearity with others owing to strong construct validity. The median all-or-none textbook outcome score was 49% (IQR 42%-54%) before and 49% (IQR 48%-51%) after case-mix adjustment. From the total of 91 hospitals, 3 hospitals were positive (3%) and 9 (10%) were negative outlier

Systematic review of targeted axillary dissection in node-positive breast cancer treated with neoadjuvant systemic therapy:variation in type of marker and timing of placement

Background: In node-positive (cN+) breast cancer treated with neoadjuvant systemic therapy, combining sentinel lymph node biopsy and targeted lymph node excision, that is targeted axillary dissection, increases accuracy. Targeted axillary dissection procedures differ in terms of the targeted lymph node excision technique. This systematic review aimed to provide an overview of targeted axillary dissection procedures regarding definitive marker type and timing of placement: before neoadjuvant systemic therapy (1-step procedure) or after neoadjuvant systemic therapy adjacent to a clip placed before the neoadjuvant therapy (2-step procedure). Methods: PubMed and Embase were searched, to 4 July 2023, for RCTs, cohort studies, and case-control studies with at least 25 patients. Studies of targeted lymph node excision only (without sentinel lymph node biopsy), or where intraoperative localization of the targeted lymph node was not attempted, were excluded. For qualitative synthesis, studies were grouped by definitive marker and timing of placement. The targeted lymph node identification rate was reported. Study quality was assessed using a National Institutes of Health quality assessment tool.Results: Of 277 unique records, 51 studies with a total of 4512 patients were included. Six definitive markers were identified: wire, 125I-labelled seed, 99mTc, (electro)magnetic/radiofrequency markers, black ink, and a clip. Fifteen studies evaluated one-step procedures, with the identification rate of the targeted lymph node at surgery varying from 8 of 13 to 47 of 47. Forty-one studies evaluated two-step procedures, with the identification rate of the clipped targeted lymph node on imaging after neoadjuvant systemic therapy varying from 49 to 100%, and the identification rate of the targeted lymph node at surgery from 17 of 24 to 100%. Most studies (40 of 51) were rated as being of fair quality.Conclusion: Various targeted axillary dissection procedures are used in clinical practice. Owing to study heterogeneity, the optimal targeted lymph node excision technique in terms of identification rate and feasibility could not be determined. Two-step procedures are at risk of not identifying the clipped targeted lymph node on imaging after neoadjuvant systemic therapy.</p

Margin assessment during breast conserving surgery using diffuse reflectance spectroscopy

Significance: During breast-conserving surgeries, it is essential to evaluate the resection margins (edges of breast specimen) to determine whether the tumor has been removed completely. In current surgical practice, there are no methods available to aid in accurate real-time margin evaluation.Aim: In this study, we investigated the diagnostic accuracy of diffuse reflectance spectroscopy (DRS) combined with tissue classification models in discriminating tumorous tissue from healthy tissue up to 2 mm in depth on the actual resection margin of in vivo breast tissue.Approach: We collected an extensive dataset of DRS measurements on ex vivo breast tissue and in vivo breast tissue, which we used to develop different classification models for tissue classification. Next, these models were used in vivo to evaluate the performance of DRS for tissue discrimination during breast conserving surgery. We investigated which training strategy yielded optimum results for the classification model with the highest performance.Results: We achieved a Matthews correlation coefficient of 0.76, a sensitivity of 96.7% (95% CI 95.6% to 98.2%), a specificity of 90.6% (95% CI 86.3% to 97.9%) and an area under the curve of 0.98 by training the optimum model on a combination of ex vivo and in vivo DRS data.Conclusions: DRS allows real-time margin assessment with a high sensitivity and specificity during breast-conserving surgeries.</p

Association between initiation of adjuvant chemotherapy beyond 30 days after surgery and overall survival among patients with triple-negative breast cancer

Delayed time to chemotherapy (TTC) is associated with decreased outcomes of breast cancer patients. Recently, studies suggested that the association might be subtype-dependent and that TTC within 30 days should be warranted in patients with triple-negative breast cancer (TNBC). The aim of the current study is to determine if TTC beyond 30 days is associated with reduced 10-year overall survival in TNBC patients. We identified all TNBC patients diagnosed between 2006 and 2014 who received adjuvant chemotherapy in the Netherlands. We distinguished between breast-conserving surgery (BCS) vs. mastectomy given the difference in preoperative characteristics and outcomes. The association was estimated with hazard ratios (HRs) using propensity-score matched Cox proportional hazard analyses. In total, 3,016 patients were included. In matched patients who underwent BCS (n = 904), 10-year overall survival was favorable for patients with TTC within 30 days (84.4% vs. 76.9%, p = 0.001). Patients with TTC beyond 30 days were more likely than those with TTC within 30 days to die within 10 years after surgery (HR 1.69 (95% CI 1.22–2.34), p = 0.002). In matched patients who underwent mastectomy (n = 1,568), there was no difference in 10 years overall survival between those with TTC within or beyond 30 days (74.5% vs. 74.7%, p = 0.716), nor an increased risk of death for those with TTC beyond 30 days (HR 1.04 (95% CI 0.84–1.28), p = 0.716). Initiation of adjuvant chemotherapy beyond 30 days is associated with decreased 10 years overall survival in TNBC patients who underwent BCS. Therefore, timelier initiation of chemotherapy in TNBC patients undergoing BCS seems warranted

Diffuse reflectance spectroscopy for accurate margin assessment in breast-conserving surgeries:importance of an optimal number of fibers

During breast-conserving surgeries, it remains challenging to accomplish adequate surgical margins. We investigated different numbers of fibers for fiber-optic diffuse reflectance spectroscopy to differentiate tumorous breast tissue from healthy tissue ex vivo up to 2 mm from the margin. Using a machine-learning classification model, the optimal performance was obtained using at least three emitting fibers (Matthew's correlation coefficient (MCC) of 0.73), which was significantly higher compared to the performance of using a single-emitting fiber (MCC of 0.48). The percentage of correctly classified tumor locations varied from 75% to 100% depending on the tumor percentage, the tumor-margin distance and the number of fibers.</p

Method for Multiple Portal Vein Infusions in Mice: Quantitation of Adenovirus-Mediated Hepatic Gene Transfer

For many preclinical studies, the mouse has been an invaluable model. For hepatic studies, including gene therapy, the use of the mouse has been limited because of the inability to obtain long-term portal vein access. In this study, we have developed a surgical cannula model that allows for repeat portal vein infusion in a noninvasive manner. We have used this model to establish that the tissue distribution of recombinant adenoviral vectors is similar after portal vein or peripheral vein infusion. The majority of the vector was present in the liver, ranging from 14 to 28 copies per hepatocyte. The second most prevalent tissues were the spleen and lung with 1/10 less adenoviral DNA. The brain and ovaries had the least DNA, 1/1000 less than the liver. Additional studies were performed to study the effects of secondary adenovirus infusion through the portal vein cannula. Permanent portal vein access in a mouse model will be invaluable for a large number of medical studies, including the development of new technologies for hepatic gene transfer

MINImal vs. MAXimal Invasive Axillary Staging and Treatment After Neoadjuvant Systemic Therapy in Node Positive Breast Cancer: Protocol of a Dutch Multicenter Registry Study (MINIMAX)

Background : Node positive breast cancer (cN+) patients with an axillary pathologic complete response after neoadjuvant systemic therapy (NST) are not expected to benefit from axillary lymph node dissection (ALND). Therefore, less invasive axillary staging procedures have been introduced to establish response-guided treatment. However, evidence is lacking with regard to their oncologic safety and impact on quality of life (QoL). We hypothesize that if response-guided treatment is given, less invasive staging procedures are non-inferior to standard ALND in terms of oncologic safety, and superior to standard ALND in terms of QoL. Patients and Methods : MINIMAX is a Dutch multicenter registry study that includes patients with cN1-3M0 unilateral invasive breast cancer, who receive NST, followed by axillary staging and treatment according to local protocols. In a retrospective registry of ±4000 patients, the primary endpoint is oncologic safety at 5 and 10 years (disease-free, breast-cancer-specific and overall survival, and axillary recurrence rate). In a prospective multicenter registry, the primary endpoints are QoL at 1 and 5 years, and we aim to verify the 5-year oncologic safety. With an estimated 5-year disease-free survival of 72.5% and anticipated loss to follow-up of 10%, a sample size of 549 is needed to have 80% power to detect non-inferiority (with a 10% margin) of less invasive staging procedures. Conclusion : In cN+ patients treated with NST, less invasive axillary staging procedures are already implemented globally. Evidence is needed to support the assumed oncologic safety and superior QoL of such procedures. This study will contribute to evidence-based guidelines