The Use of Machine Learning to Reduce Overtreatment of the Axilla in Breast Cancer: Retrospective Cohort Study.

BACKGROUND: Patients with early breast cancer undergoing primary surgery, who have low axillary nodal burden, can safely forego axillary node clearance (ANC). However, routine use of axillary ultrasound (AUS) leads to 43% of patients in this group having ANC unnecessarily, following a positive AUS. The intersection of machine learning with medicine can provide innovative ways to understand specific risks within large patient data sets, but this has not yet been trialed in the arena of axillary node management in breast cancer. OBJECTIVE: The objective of this study was to assess if machine learning techniques could be used to improve preoperative identification of patients with low and high axillary metastatic burden. METHODS: A single-center retrospective analysis was performed on patients with breast cancer who had a preoperative AUS, and the specificity and sensitivity of AUS were calculated. Standard statistical methods and machine learning methods, including artificial neural network, naive Bayes, support vector machine, and random forest, were applied to the data to see if they could improve the accuracy of preoperative AUS to better discern high and low axillary burden. RESULTS: The study included 459 patients; 142 (31%) had a positive AUS; among this group, 88 (62%) had 2 or fewer macrometastatic nodes at ANC. Logistic regression outperformed AUS (specificity 0.950 vs 0.809). Of all the methods, the artificial neural network had the highest accuracy (0.919). Interestingly, AUS had the highest sensitivity of all methods (0.777), underlining its utility in this setting. CONCLUSIONS: We demonstrated that machine learning improves identification of the important subgroup of patients with no palpable axillary disease, positive ultrasound, and more than 2 metastatically involved nodes. A negative ultrasound in patients with no palpable lymphadenopathy is highly indicative of low axillary burden, and it is unclear whether sentinel node biopsy adds value in this situation. Further studies with larger patient numbers focusing on specific breast cancer subgroups are required to refine these techniques in this setting.

Non-invasive predictors of axillary lymph node burden in breast cancer: a single-institution retrospective analysis.

PURPOSE: Axillary staging is an important prognostic factor in breast cancer. Sentinel lymph node biopsy (SNB) is currently used to stage patients who are clinically and radiologically node-negative. Since the establishment that axillary node clearance (ANC) does not improve overall survival in breast-conserving surgery for patients with low-risk biological cancers, axillary management has become increasingly conservative. This study aims to identify and assess the clinical predictive value of variables that could play a role in the quantification of axillary burden, including the accuracy of quantifying abnormal axillary nodes on ultrasound. METHODS: A retrospective analysis was conducted of hospital data for female breast cancer patients receiving an ANC at our centre between January 2018 and January 2020. The reference standard for axillary burden was surgical histology following SNB and ANC, allowing categorisation of the patients under 'low axillary burden' (2 or fewer pathological macrometastases) or 'high axillary burden' (> 2). After exploratory univariate analysis, multivariate logistic regression was conducted to determine relationships between the outcome category and candidate predictor variables: patient age at diagnosis, tumour focality, tumour size on ultrasound and number of abnormal lymph nodes on axillary ultrasound. RESULTS: One hundred and thirty-five patients were included in the analysis. Logistic regression showed that the number of abnormal lymph nodes on axillary ultrasound was the strongest predictor of axillary burden and statistically significant (P = 0.044), with a sensitivity of 66.7% and specificity of 86.8% (P = 0.011). CONCLUSION: Identifying the number of abnormal lymph nodes on preoperative ultrasound can help to quantify axillary nodal burden and identify patients with high axillary burden, and should be documented as standard in axillary ultrasound reports of patients with breast cancer.

Breast MRI in patients after breast conserving surgery with sentinel node procedure using a superparamagnetic tracer.

BACKGROUND: A procedure for sentinel lymph node biopsy (SLNB) using superparamagnetic iron-oxide (SPIO) nanoparticles and intraoperative sentinel lymph node (SLN) detection was developed to overcome drawbacks associated with the current standard-of-care SLNB. However, residual SPIO nanoparticles can result in void artefacts at follow-up magnetic resonance imaging (MRI) scans. We present a grading protocol to quantitatively assess the severity of these artefacts and offer an option to minimise the impact of SPIO nanoparticles on diagnostic imaging. METHODS: Follow-up mammography and MRI of two patient groups after a magnetic SLNB were included in the study. They received a 2-mL subareolar dose of SPIO (high-dose, HD) or a 0.1-mL intratumoural dose of SPIO (low-dose, LD). Follow-up mammography and MRI after magnetic SLNB were acquired within 4 years after breast conserving surgery (BCS). Two radiologists with over 10-year experience in breast imaging assessed the images and analysed the void artefacts and their impact on diagnostic follow-up. RESULTS: A total of 19 patients were included (HD, n = 13; LD, n = 6). In the HD group, 9/13 patients displayed an artefact on T1-weighted images up to 3.6 years after the procedure, while no impact of the SPIO remnants was observed in the LD group. CONCLUSIONS: SLNB using a 2-mL subareolar dose of magnetic tracer in patients undergoing BCS resulted in residual artefacts in the breast in the majority of patients, which may hamper follow-up MRI. This can be avoided by using a 0.1-mL intratumoural dose.

Axillary dissection versus axillary observation for low risk, clinically node-negative invasive breast cancer: a systematic review and meta-analysis.

PURPOSE: 1. To systematically analyse studies comparing survival outcomes between axillary lymph-node dissection (ALND) and axilla observation (Obs), in women with low-risk, clinically node-negative breast cancer. 2. To consider results in the context of current axillary surgery de-escalation trials and studies. METHODS: 9 eligible studies were identified, 6 RCTs and 3 non-randomized studies (4236 women in total). Outcomes assessed: overall survival (OS) and disease-free survival (DFS). The logged (ln) hazard ratio (HR) was calculated and used as the statistic of interest. Data was grouped by follow-up. RESULTS: Meta-analyses found no significant difference in OS at 5, 10 and 25-years follow-up (5-year ln HR = 0.08, 95% CI - 0.09, 0.25, 10-year ln HR = 0.33, 95% CI - 0.07, 0.72, 25-year ln HR = 0.00, 95% CI - 0.18, 0.19). ALND caused improvement in DFS at 5-years follow-up (ln HR = 0.16, 95% CI 0.03, 0.29), this was not demonstrated at 10 and 25-years follow-up (10-year ln HR = 0.07, 95% CI - 0.09, 0.23, 25-year ln HR = - 0.03, 95% CI - 0.21, 0.16). Studies supporting ALND for DFS at 5-years follow-up had greater relative chemotherapy use in the ALND cohort. CONCLUSION: ALND does not cause a significant improvement in OS in women with clinically node-negative breast cancer. ALND may improve DFS in the short term by tailoring a proportion of patients towards chemotherapy. Our evidence suggests that when the administration of systemic therapy is balanced between the two arms, axillary de-escalation studies will likely find no difference in OS or DFS.

A systematic review of neo-adjuvant radiotherapy in the treatment of breast cancer.

INTRODUCTION: The use of neo-adjuvant radiotherapy (NRT) has been proven effective at improving cancer related outcome measures, including overall-survival (OS) in the management of solid cancers. However, its utilisation in breast cancer has not been explored to the extent of neo-adjuvant chemotherapy (NAC). The evidence for the application of NRT in breast cancer is evaluated. METHODS: PubMed, Embase and the Cochrane Library databases were searched systematically in August 2020 for studies that addressed the role of NRT in the treatment of breast cancer. Studies were deemed eligible if they reported on objective outcome measurements of OS, disease free-survival (DFS) or pathological complete response (pCR) and attained a satisfactory quality assessment. FINDINGS: A total of 23 studies reported upon 3,766 patients who had received NRT of which 3,233 also received NAC concurrently (neo-adjuvant chemo-radiotherapy (NCRT)). The pCR values ranged from 14% to 42%, 5-year DFS 61.4% to 81% and 5-year OS 71.6% to 84.2%. Complications were confined to radiation dermatitis with no cases of implant loss reported during breast reconstruction. The application of NRCT alone showed no significant difference in OS or DFS compared to NCRT followed by surgery. INTERPRETATION: Numbers of patients receiving exclusively NRT is small. However, NCRT is oncologically safe with a low side-effect profile including preceding breast reconstruction. Potential benefits include precise cancer volume targeting, chemosensitisation, elimination of delays in adjuvant therapies and alternatives to chemotherapy in oestrogen receptor positive patients. These factors warrant further exploration within randomised controlled-trials.

Biosensors as a future diagnostic approach for COVID-19.

Biosensors are important devices in clinical diagnostics, food processing, and environmental monitoring for detecting various analytes, especially viruses. These biosensors provide rapid and effective instruments for qualitative and quantitative detection of infectious diseases in real-time. Here, we report the development of biosensors based on various techniques. Additionally, we will explain the mechanisms, advantages, and disadvantages of the most common biosensors that are currently used for viral detection, which could be optical (e.g., surface-enhanced Raman scattering (SERS), Surface plasmon resonance (SPR)) and electrochemical biosensors. Based on that, this review recommends methods for efficient, simple, low-cost, and rapid detection of SARS-CoV-2 (the causative agent of COVID-19) that employ the two types of biosensors depending on attaching hemoglobin ß-chain and binding of specific antibodies with SARS-CoV-2 antigens, respectively.

Conserving the axilla in breast cancer.

It is recognised that surgical conservatism is the most effective way of managing the axilla in breast cancer patients undergoing primary breast conserving surgery. The extended clinical scenarios in which a less aggressive approach can be safely adopted warrant consideration-including a group of patients who potentially could bypass surgical staging of the axilla altogether. The application of omission of further surgical management and axillary radiotherapy in the primary surgical and neoadjuvant chemotherapy settings are considered.

Do soil property variations affect dicyandiamide efficiency in inhibiting nitrification and minimizing carbon dioxide emissions?

Nitrification inhibitors (NIs) are used to retard the nitrification process and reduce nitrogen (N) losses. However, the effects of soil properties on NI efficacy are less clear. Moreover, the direct and indirect effects of soil property variations on NI efficiency in minimizing carbon dioxide (CO2) emissions have not been previously studied. An incubation experiment was conducted for 40 days with two treatments, N (200 mg N-urea kg-1) and N + dicyandiamide (DCD) (20 mg DCD kg-1), and a control group (without the N) to investigate the response of ammonia-oxidizing bacteria (AOB) and archaea (AOA) to DCD application and the consequences for CO2, nitrous oxide (N2O) and ammonia (NH3) emissions from six soils from the Loess Plateau with different properties. The nitrification process completed within 6-18 days for the N treatment and within 30->40 days for the N + DCD treatment. AOB increased significantly with N fertilizer application, while this effect was inhibited in soils when DCD was applied. AOA was not sensitive to N fertilizer and DCD application. The nitrification rate was positively correlated with the clay (p < 0.05) and SOM contents (p < 0.01); DCD was more effective in loam soil with low SOM and high soil pH. Soil pH significantly was decreased with N fertilizer application, while it increased when DCD was applied. Moreover, DCD application decreased CO2 emissions from soils by 22%-172%; CO2 emissions were negatively correlated with the clay and SOM contents. DCD application decreased N2O emissions in each soil by 1.0- to 94-fold compared with those after N fertilizer application. In contrast, DCD application increased NH3 release from soils by 59-278%. NH3 volatilization was negatively correlated with clay (p < 0.05) and SOM (p < 0.01) contents and positively correlated with soil pH (p < 0.01). Therefore, soil texture, SOM and soil pH have significant effects on the DCD performance, nitrification process and gaseous emissions.

Residual effects of tobacco biochar along with different fixing agents on stabilization of trace elements in multi-metal contaminated soils.

The residual effect of tobacco biochar (TB ≥ 500°C) mono and co-application with Ca-hydroxide (CH), Ca-bentonite (CB) and natural zeolite (NZ) on the bio-availability of trace elements TE(s) in alkaline soils has not been deeply studied yet. A pot study that had earlier been investigated TB mono and blended with CH, CB and NZ on the immobilization of Pb, Cu Cd, and Zn by Chinese cabbage. Maize crop in the rotation was selected as test plant to assess the residual impact of amendments on stabilization of Pb, Cu Cd, and Zn in mine polluted (M-P), smelter heavily and low polluted (S-HP and S-LP, respectively) soils. The obtained results showed that stabilization of Pb, Cd, Cu and Zn reached 63.84% with TB + CB, 61.19% with TB + CH, 83.31% with TB + CH and 35.27% with TB + CH for M-P soil, 36.46% with TB + NZ, 38.46% with TB + NZ, 19.40% with TB + CH and 62.43% with TB + CH for S-LP soil, 52.94% TB + NZ, 57.65% with TB + NZ, 52.94% with TB + NZ, and 28.44% with TB + CH for S-LP soil. Conversely, TB + CH and TB alone had mobilized Pb and Zn up to 19.29% and 34.96% in M-P soil. The mobility of Zn reached 8.38% with TB + CB and 66.03% with TB for S-HP and S-LP soils. The uptake and accumulation of Pb, Cd, Cu and Zn in shoot and root were reduced in three polluted soils. Overall, the combination of TB along with CH, CB and NZ has been proven to be effective in Pb, Cd, Cu and Zn polluted mine/smelter soils restoration.

An evaluation of access to critical breast oncoplastic patient information within a regional autologous free-flap reconstruction service.

The configuration of autologous free-flap breast reconstruction services within regional hubs means that increasing numbers of patients operated upon at these units will be external referrals without their oncological investigations carried out at the tertiary receiving centre. Oncoplastic guidelines exist that clearly state the minimum necessary patient information that should be provided by the referring unit to the reconstruction centre. However, the logistics of such critical information transfer can be challenging, but it is essential that such issues are addressed to ensure safe oncological management of patients undergoing autologous breast reconstruction.

Is sentinel node biopsy necessary in the radiologically negative axilla in breast cancer?

PURPOSE: The steady move towards axillary conservatism in breast cancer is based on studies demonstrating that axillary node clearance affords no survival benefit in a subset of patients with a positive pre-operative axillary ultrasound (AUS). However, less attention has been paid to AUS-negative patients who receive sentinel node biopsy as standard. METHODS: Previously assembled systematic review data was reassessed to evaluate nodal burden amongst patients with breast cancer and a clinically and radiologically negative axilla. RESULTS: Pooled data from four cohort studies reporting pre-operative axillary ultrasound in 5139 patients with breast cancer show it has a negative predictive rate of 0.951 (95% confidence interval 0.941-0.960). CONCLUSIONS: Reconsidering the use of ultrasound in patients with early breast cancer and non-palpable axillae reveals that sentinel node biopsy itself may represent surgical over-treatment in patients with a negative axillary ultrasound. The implications of this on the future of surgical management of the axilla are discussed.

Current state of surgical management for male breast cancer.

Management guidelines for male breast cancer have long been extrapolated from those for female breast cancer, which are based on large, randomised-controlled trials. While there are no randomised-controlled trials for male breast cancer management mainly due to the rarity of the disease, the only type of evidence available comes from retrospective studies, subject to selection biases and small sample sizes. Male breast cancer, while similar to female breast cancer in many respects, has some important differences that can affect management choices. Most cancers are oestrogen and progesterone receptor positive, and usually more advanced at presentation than female breast cancer. This is likely due to less breast parenchyma in male patients and delay to diagnosis. The classical management option for male patients with breast cancer is mastectomy, due to small tumour-to-breast ratio and often central position of the tumour. Breast conserving surgery is still useful in selected cases and has similar outcomes when compared to mastectomies in these patients. For patients with clinically negative lymph nodes, sentinel lymph node biopsy offers the same prognosis as axillary lymph node dissection, but with less associated morbidity. Endocrine therapy is of particular use, due to high levels of receptor positivity. Adjuvant endocrine therapy seems to significantly improve overall survival of male patients with breast cancer and while no prospective evidence exists for neoadjuvant hormonal therapy, there is hope that this is a useful management option as well. Radiotherapy is also useful in an adjuvant setting, particularly when combined with endocrine therapy. Better identification of patients, less delay from presentation to diagnosis and more collaborative efforts are key in improving the management, prognosis and outcomes of patients with male breast cancer.

Rare epithelial breast cancer: surgery and adjuvant therapy.

Breast cancer is a heterogenous disease, exhibiting a wide range of morphological phenotypes shaping its prognosis and clinical course. However, optimal management of rarer breast cancer subtypes is often undefined and controversial in literature due to the lack of large studies and randomised trials. This review aims to discuss the treatment of 13 rare epithelial subtypes, focussing on surgery and adjuvant therapies.

Combined use of fluorescence with a magnetic tracer and dilution effect upon sentinel node localization in a murine model.

BACKGROUND: Sentinel node biopsy using radioisotope and blue dye remains a gold standard for axillary staging in breast cancer patients with low axillary burden. However, limitations in the use of radioisotopes have resulted in emergence of novel techniques. This is the first in vivo study to assess the feasibility of combining the two most common novel techniques of using a magnetic tracer and indocyanine green (ICG) fluorescence. MATERIALS AND METHODS: A total of 48 mice were divided into eight groups. Groups 1 and 2, the co-localization groups, received an injection of magnetic tracers (Resovist® and Sienna+®, respectively) and ICG fluorescence; distilled water was used as the solvent of ICG. Groups 3 and 4, the diluted injection groups, received an injection of magnetic tracers (Resovist and Sienna+, respectively) and saline for dilution. Groups 5, 6, and 7, the control groups, received magnetic tracer (Resovist, Sienna+) and ICG alone, respectively. Fluorescent intensity assessment and iron quantification of excised popliteal lymph nodes were performed. Group 1', a co-localization group, received an injection of magnetic tracers (Resovist) and ICG' fluorescence: saline was used as the solvent for ICG. RESULTS: Lymphatic uptake of all tracers was confined to the popliteal nodes only, with co-localization confirmed in all cases and no significant difference in fluorescent intensity or iron content of ex vivo nodes between the groups (except for Group 1'). There was no impact of dilution on the iron content in the diluted Sienna+ group, but it significantly enhanced Resovist uptake (P=0.005). In addition, there was a significant difference in iron content (P=0.003) in Group 1'. CONCLUSION: The combination of a magnetic tracer (Resovist or Sienna+) and ICG fluorescence is feasible for sentinel node biopsy and will potentially allow for precise transcutaneous node identification, in addition to accurate intraoperative assessment. This radioisotope-free "combined technique" warrants further assessment within a clinical trial.

Meta-analysis of tumour burden in pre-operative axillary ultrasound positive and negative breast cancer patients.

BACKGROUND: Management of the axilla in breast cancer is becoming increasingly conservative. Patients identified with a low axillary nodal burden (two or fewer involved nodes) at sentinel node biopsy (SNB) can avoid completion axillary node clearance (cANC). 'Fast track' to ANC in patients with involved nodes on pre-operative ultrasound may be over-treating a subgroup of these patients with low nodal burden, which would have precluded their need for ANC. This systematic review assesses the proportion of patients with involved nodes on pre-operative axillary ultrasound, which would fit low axillary burden criteria. METHODS: Meta-analysis of studies comparing axillary burden of breast cancer patients identified as pre-operative ultrasound negative versus positive was performed. The primary outcome measure was the number of patients with two or fewer involved nodes (macrometastases only). Pooled odds ratio (OR), 95% confidence intervals (CIs), means and probabilities of identifying two or fewer involved nodes versus greater than two were calculated. RESULTS: Six studies reported the axillary burden in 4271 patients who were either directed straight to ANC or cANC after SNB. There was a significantly greater axillary burden in the ultrasound positive versus negative groups (OR 5.95, 95% CI 5.80-6.11) with mean nodal retrieval values of 2.9 [standard error (SE) 0.2] and 1.6 (SE 0.2) nodes, respectively. Cumulative probabilities identified 78.9% of ultrasound negative and 43.2% of ultrasound positive patients possessed low axillary burden. CONCLUSIONS: Pre-operative ultrasound positive patients have significantly higher axillary burden. However, nearly half do fit the criteria of low axillary burden and could be considered for omission of ANC.

Minimally invasive ablative techniques in the treatment of breast cancer: a systematic review and meta-analysis.

PURPOSE: Breast-conserving surgery is effective for breast cancer treatment but is associated with morbidity in particular high re-excision rates. We performed a systematic review and meta-analysis to assess the current evidence for clinical outcomes with minimally invasive ablative techniques in the non-surgical treatment of breast cancer. METHODS: A systematic search of the literature was performed using PubMed and Medline library databases to identify all studies published between 1994 and May 2016. Studies were considered eligible for inclusion if they evaluated the role of ablative techniques in the treatment of breast cancer and included ten patients or more. Studies that failed to fulfil the inclusion criteria were excluded. RESULTS: We identified 63 studies including 1608 patients whose breast tumours were treated with radiofrequency (RFA), high intensity focussed ultrasound (HIFU), cryo-, laser or microwave ablation. Fifty studies reported on the number of patients with complete ablation as found on histopathology and the highest rate of complete ablation was achieved with RFA (87.1%, 491/564) and microwave ablation (83.2%, 89/107). Short-term complications were most often reported with microwave ablation (14.6%, 21/144). Recurrence was reported in 24 patients (4.2%, 24/570) and most often with laser ablation (10.7%, 11/103). The shortest treatment times were observed with RFA (15.6 ± 5.6 min) and the longest with HIFU (101.5 ± 46.6 min). CONCLUSION: Minimally invasive ablative techniques are able to successfully induce coagulative necrosis in breast cancer with a low side effect profile. Adequately powered and prospectively conducted cohort trials are required to confirm complete pathological ablation in all patients.