Anushka Chaudhry

The real-time intra-operative evaluation of sentinel lymph nodes in breast cancer patients using One Step Nucleic Acid Amplification (OSNA) and implications for clinical decision-making.

INTRODUCTION One Step Nucleic Acid Amplification (OSNA) method for the intraoperative analysis of sentinel lymph nodes (SLNs) in breast cancer, obviates a second operation to the axilla and thereby expedites progression to adjuvant therapy. Recent NICE guidelines have approved OSNA as a method of sentinel node diagnosis to support the above case.(1) METHOD: This is a single centre prospective cohort analysis of all patients undergoing breast cancer surgery including sentinel node biopsy from February 2010 to June 2012. Patients with negative SLN(s) on OSNA had no further axillary surgery. A validation phase was performed prior to using OSNA routinely. Those with micrometastases underwent a level 1 clearance, and >one SLN with macrometastases, underwent treatment by level 2 axillary dissection. The length of time from sentinel node retrieval to OSNA result was recorded. RESULTS Four hundred and forty nodes were analysed in 212 patients with a mean age of 55 years (range 24-98). The sensitivity and specificity of OSNA was 93% and 94% respectively in cases of macrometastases. The process required additional median anaesthesia time of 20 min (range -48 to +65 min). Non-sentinel node positivity was 5% and 48% for micrometastasis and macrometastasis respectively. CONCLUSION OSNA identified 62 of 212 patients with at least one positive sentinel node, thereby sparing 29% from a second procedure to clear the axilla subsequently. The median waiting time of 20 min for node results from completion of breast procedure is acceptable and allows for an efficient operating list. OSNA can be incorporated into routine practice and with improved methods of imaging preoperatively, can be an excellent adjunct to the breast cancer patient pathway of care.

P2-16-06: A Systematic Review of Standardised Clinical Outcomes and Patient Reported Outcome Measures (PROMS) in Breast Reconstruction.

Introduction: Failure to prospectively define and report surgical complications across a range of study designs is a confounding factor that fundamentally compromises the interpretation of data on health-related quality of life (HRQL) and PROMS. The UK National Mastectomy and Breast Reconstruction audit on 5000 breast reconstruction patients found higher than expected levels of complications (including rates of reoperation and levels of infection). We aimed to analyze the reporting of complications in a systematic review of all studies evaluating PROMS in breast reconstruction since 1978 1 . Methods: Efficace criteria for HRQL methodology were used to assess the inclusion eligibility for each study 1 . Two out of 34 eligible studies were excluded due to overlapping patient datasets and small numbers (n 2 and their integration into the evaluation of PROMS results. RS were evaluated for the reporting of complications and their statistical methodology. Results: A total of 3213 patients were included in the 32 studies. The type of reconstruction was only recorded in 71% of patients. The majority of patients in these studies underwent abdominal flap reconstruction, compared to implant only techniques (32%), and less than 10% comprising Latissimus dorsi flaps. Only 19% of studies recorded complications with the majority (81%) failing to report any complications. Only 3 studies provided details of the numbers and level of complications amongst a total of 44 patients (1.4% of the total number of patients). Reported complications were graded and classified either as major (requiring surgical intervention) or minor comprising 55% and 45%, respectively. None of the RCT or PLS studies defined either the type or level of complications a priori, nor stratified complications based on risk factors such as age, body mass index, smoking and diabetes. Conclusion: There is a significant under estimation of the contribution of complications to HRQL and PROMS reporting. This fact diminishes the current evidence on the effects of breast reconstruction on PROMS. There should be collective efforts to improve the standards of documentation for clinical outcomes in breast reconstruction. This together with standardized reporting of PROMS will consolidate clinical evidence upon which decision-making and provision of patient information can be confidently based. 1. Winters ZE, Benson JR, Pusic AL. Annals of Surgery 2010;252(6):929–42 2. Dindo D et al. Annals of Surgery 2004;240(2):205–213 Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-16-06.

P2-16-01: A Multi-Centre Prospective Cohort Study Evaluating Health Related Quality of Life after Types of Immediate Latissimus Dorsi (LD) Breast Reconstruction.

Introduction : Evidence for the clinical effectiveness of breast reconstruction based on Patient Reported Outcome Measures (PROMS) is lacking. Methodology evaluating PROMS after types of breast reconstruction has been poor with respect to study design, statistics, missing data and absence of prospective documentation of pre-defined complication data in a systematic review of all studies since 1978 1 . Furthermore, there is no reliable data on the effects of associated radiotherapy (RT) in this context. As a prelude to a proposed randomised trial in breast reconstruction, our aim was to conduct a ‘robust’ cohort study evaluating the effects of either implant-assisted LD (LDI) or tissue only (ALD) LD flap reconstruction in relation to key determinants including clinico-pathological parameters, complications and treatment schedules over a 36 month period. Methods : An MREC approved prospective longitudinal cohort study involving 6 centres commenced in early 2007. Serial PROMS using the EORTC QLQ-C30, BR-23, FACT-B, BIS and HADS, were completed pre-operatively and at 3, 6, 12, 24 and 36 months after surgery. Data up to 12 months were included in this analysis as data were sparse beyond this point; follow-up is ongoing. Demographic and clinical data were compared between the surgical groups. Generalised estimating equations were used to investigate demographic and clinical predictors of HRQL over time. Results : A total of 189 patients (107-ALD, 82-LDI) were recruited, with a mean age of 50 years (range 22–70). Baseline questionnaires were completed by 149 (79%) women, with 167 (88%) available at 12 months. Patients in the ALD group had a higher BMI (mean 27.3 versus 25.2 in LDI, p=0.001) and a greater likelihood of post-mastectomy RT (52% versus 30% in LDI, p=0.004). Only role functioning (p=0.001) and pain (p=0.003) were significantly adversely affected in the ALD v LDI group, with no statistically significant effects from PMRT on HRQL, although chemotherapy impaired global QoL (p Conclusion : There is increasing evidence of clinical equipoise between types of LD breast reconstruction and despite acknowledged cosmetic disadvantages the overall effects of PMRT on HRQL are minimal. The identification of important variables that may affect HRQL is crucial in all studies evaluating the effects of surgery on PROMS. Their integration into study results is essential for correct interpretation of clinically based assessments. This remains a challenging aspect in cohort studies, and emphasises the need for pragmatism in design of trials in the field. 1. Winters ZE, Benson JR, Pusic AL. Annals of Surgery 2010;252(6):929–42 Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-16-01.

P3-07-23: Intraoperative Molecular Analysis of Sentinel Lymph Nodes in Breast Cancer Using One Step Nucleic Acid Amplification (OSNA).

Abstracts: Thirty-Fourth Annual CTRC‐AACR San Antonio Breast Cancer Symposium‐‐ Dec 6‐10, 2011; San Antonio, TX Introduction: The OSNA method for the intra-operative analysis of sentinel lymph nodes (SLNs) in breast cancer has been introduced in 3 UK centres since 2007. The methodology uses a polymerase chain reaction to quantitate CK19, a cytokeratin specific to breast duct epithelial cells. OSNA provides “real-time” results on SLNs analysed as negative (−) or positive with either micro (+) or macrometastases (++). Method: This is a single-centre prospective pilot study of all patients undergoing breast cancer surgery including sentinel node biopsy from February 2010 to May 2011. SLN identification was performed using a dual localization technique with peri-areolar Patente V blue dye and Tc99 radio-active isotope. SLNs were cut into 4 slices labeled as A, B, C and D, respectively after the removal of all perinodal fat. In all SLNs, slices A and C were processed in OSNA and slices B and D underwent histological assessment by HE 23 mastectomies and 22 SLNB alone. The mean time for OSNA was 40.5, 51.8, 54 and 61.5 minutes for 1,2,3, and 4 sentinel lymph nodes respectively. Operation time was prolonged by a median of 20 minutes (range −48 to +65 minutes) WLEs were delayed by the greatest time Exclusions: Nodes that were not available for histological comparison i) nodes weighing <0.05g (n=34) were processed whole. ii) Departmental agreement from mid March 2011 to process nodes whole via OSNA (n=51); 6 had micro or macrometastases. Conclusion: OSNA prevented staged axillary surgery in 24 (21%) of patients. A median time of 20 minutes for the OSNA procedure is comparable with acceptable operating times. Current experience supports the use of OSNA for each individual whole SLN analysis. The pilot data has resulted in a prescribed change in policy to analyse the whole SLN using this technique. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-23.