Shramana Banerjee

Detailed evaluation of one step nucleic acid (OSNA) molecular assay for intra-operative diagnosis of sentinel lymph node metastasis and prediction of non-sentinel nodal involvement: Experience from a London Teaching Hospital

One step nucleic acid (OSNA) is a molecular diagnostic assay for intra-operative detection of sentinel node metastases. This study compared OSNA with standard histopathology in 283 nodes from 170 patients to evaluate sensitivity, specificity and concordance of the two methods. Additional analysis was done to investigate how cytokeratin 19 mRNA copy number affects prediction of non-sentinel node positivity. OSNA sensitivity was 93.2% and specificity 95.8%. Concordance between OSNA and histology was 95.6%. In the patients who had axillary clearance, the OSNA mRNA copy number on the sentinel node had 100% negative predictive value for histologically proven metastasis. mRNA copy numbers <1400 were not associated with histologically proven metastasis in subsequent nodes at axillary clearance. OSNA is a reliable method for the intra-operative evaluation of axillary lymph node metastasis even when half of the lymph node is used. Identification of mRNA copy number threshold predicting the positivity of non-sentinel axillary nodes seems to be feasible and would be clinically important.

The use of one-step nucleic acid amplification (OSNA) and tumor-related factors in the axillary management of breast cancer: A predictive model.

61 Background: Recent trends in surgical practice advocate selective use of axillary nodal clearance (ANC) following sentinel lymph node biopsy (SNB) in the treatment of breast cancer. We aimed to determine the effectiveness of one-step nucleic acid amplification (OSNA) using CK19 mRNA copy number and tumor-related factors in predicting non-sentinel axillary nodal involvement, in order to formulate local guidelines for ANC. METHODS Patients due to have SNB at our institution for invasive breast cancer as well as selected patients with high grade ductal carcinoma in situ with negative assessment of the axilla on pre-operative imaging were included. Alternate slices of each node were sent for assessment by either OSNA or Histopathology. Immediate ANC was performed if OSNA was positive. The CK19 mRNA copy number, the total tumor load (summation of m RNA copy number of positive nodes,TTL), the total nodal status at ANC and tumor characteristics including grade, tumor size and lymphovascular invasion (LVI) for each patient were determined. A model of risk probability was constructed using TTL and tumor related factors. RESULTS 664 nodes were examined from 425 patients who had SNB performed between 2011 and 2014. After excluding 8 patients who did not meet the study criteria, 648 nodes from 417 patients were included for analysis. The concordance between OSNA and histology was 91.4%; positive predictive value (PPV) and negative predictive value (NPV) was 77% and 97% respectively. Patients with TTL less than 1400 did not have additional non sentinel lymph node involvement. TTL (p<0.01), and presence of LVI (p<0.05) were predictive for additional nodal involvement. The risk model identified all patients with more than 2 positive nodes as requiring ANC. All patients with non-sentinel node metastases at ANC were selected. CONCLUSIONS OSNA is a sensitive and reliable intraoperative method for the detection of sentinel node metastases. Our study has shown it can also be used to predict the presence of non-sentinel metastases. Patients deemed high risk may be offered immediate ANC while axillary surgery in other groups may be omitted or be decision-based on risk stratification.

Electrochemotherapy for cutaneous metastases in breast cancer: Experience from a designated treatment centre.

48 Background: Electrochemotherapy (ECT) combines the administration of poorly permeable chemotherapeutic agents with electroporation. It has been shown to be effective when compared with other treatments. This study assessed how breast cancer patients were benefited and identified potential problems at a designated treatment centre. METHODS This was a single centre prospective study of patients with cutaneous metastases from breast cancer. Patients who fulfilled NICE UK (National Institute Of Clinical Excellence) and local guidelines were treated. Gabapentin was given prior to general anaesthesia. Intravenous Bleomycin 15,000IU/m2 was given as a bolus. Treatment was commenced 8 minutes later with Cliniporator. Electrical pulses were delivered via an electrode inserted through the skin surface. Treatment response, disease progression free duration, post-operative pain and length of in-patient stay (LOS) were recorded. Patients recorded a symptom diary post treatment. RESULTS 20 treatments were performed in 16 patients from 2011-2015 with 53 separate areas treated. 8 patients had diffuse lesions, 5 had discrete lesions and 3 had both diffuse and discrete areas. 16 patients were being treated with ECT for the first time and 4 patients required 2 treatments. Median LOS was 3 days. Median follow up was 6 months (range 3-12).12 patients had complete response (75%) and 4 patients partial response. There was no disease progression for 6 months or more in 9 patients (56%) and 2 further patients had disease stabilised for 3 months with systemic or cutaneous progression in the remaining patients in 3 months or less. There were no deaths or immediate adverse events from ECT. 5 Patients (31%) with extensive diffuse chest wall disease reported persistent discomfort post treatment requiring extended period of post treatment analgesia. CONCLUSIONS Electrochemotherapy is safe and effective treatment for cutaneous metastases. Appropriate patient selection for treatment, pre-emptive analgesia, post treatment support and follow up is essential in order to maximise the benefits and minimise potential side-effects particularly in extensive chest wall disease.