Diagnostic accuracy of intraoperative techniques for margin assessment in breast cancer surgery: a meta-analysis

OBJECTIVE: The aim of this study was to conduct a systematic review and meta-analysis to clarify the diagnostic accuracy of intraoperative breast margin assessment (IMA) techniques against which the performance of emerging IMA technologies may be compared. SUMMARY OF BACKGROUND DATA: IMA techniques have failed to penetrate routine practice due to limitations, including slow reporting times, technical demands, and logistics. Emerging IMA technologies are being developed to reduce positive margin and re-excision rates and will be compared with the diagnostic accuracy of existing techniques. METHOD: Studies were identified using electronic bibliographic searches up to January 2016. MESH terms and all-field search terms included "Breast Cancer" AND "Intraoperative" AND "Margin." Only clinical studies with raw diagnostic accuracy data as compared with final permanent section histopathology were included. A bivariate model for diagnostic meta-analysis was used to attain overall pooled sensitivity and specificity. RESULTS: Eight hundred thirty-eight unique studies revealed 35 studies for meta-analysis. Pooled sensitivity (Sens), specificity (Spec), and area under the receiver operating characteristic curve (AUROC) values were calculated per group (Sens, Spec, AUROC): frozen section = 86%, 96%, 0.96 (n = 9); cytology = 91%, 95%, 0.98 (n = 11); intraoperative ultrasound = 59%, 81%, 0.78 (n = 4); specimen radiography = 53%, 84%, 0.73 (n = 9); optical spectroscopy = 85%, 87%, 0.88 (n = 3). CONCLUSIONS: Pooled data suggest that frozen section and cytology have the greatest diagnostic accuracy. However, these methods are resource intensive and turnaround times for results have prevented widespread international adoption. Emerging technologies need to compete with the diagnostic accuracy of existing techniques while offering advantages in terms of speed, cost, and reliability

Primary radiotherapy and deep inferior epigastric perforator flap reconstruction for patients with breast cancer (PRADA): a multicentre, prospective, non-randomised, feasibility study

BACKGROUND: Radiotherapy before mastectomy and autologous free-flap breast reconstruction can avoid adverse radiation effects on healthy donor tissues and delays to adjuvant radiotherapy. However, evidence for this treatment sequence is sparse. We aimed to explore the feasibility of preoperative radiotherapy followed by skin-sparing mastectomy and deep inferior epigastric perforator (DIEP) flap reconstruction in patients with breast cancer requiring mastectomy. METHODS: We conducted a prospective, non-randomised, feasibility study at two National Health Service trusts in the UK. Eligible patients were women aged older than 18 years with a laboratory diagnosis of primary breast cancer requiring mastectomy and post-mastectomy radiotherapy, who were suitable for DIEP flap reconstruction. Preoperative radiotherapy started 3-4 weeks after neoadjuvant chemotherapy and was delivered to the breast, plus regional nodes as required, at 40 Gy in 15 fractions (over 3 weeks) or 42·72 Gy in 16 fractions (over 3·2 weeks). Adverse skin radiation toxicity was assessed preoperatively using the Radiation Therapy Oncology Group toxicity grading system. Skin-sparing mastectomy and DIEP flap reconstruction were planned for 2-6 weeks after completion of preoperative radiotherapy. The primary endpoint was the proportion of open breast wounds greater than 1 cm width requiring a dressing at 4 weeks after surgery, assessed in all participants. This study is registered with ClinicalTrials.gov, NCT02771938, and is closed to recruitment. FINDINGS: Between Jan 25, 2016, and Dec 11, 2017, 33 patients were enrolled. At 4 weeks after surgery, four (12·1%, 95% CI 3·4-28·2) of 33 patients had an open breast wound greater than 1 cm. One (3%) patient had confluent moist desquamation (grade 3). There were no serious treatment-related adverse events and no treatment-related deaths. INTERPRETATION: Preoperative radiotherapy followed by skin-sparing mastectomy and immediate DIEP flap reconstruction is feasible and technically safe, with rates of breast open wounds similar to those reported with post-mastectomy radiotherapy. A randomised trial comparing preoperative radiotherapy with post-mastectomy radiotherapy is required to precisely determine and compare surgical, oncological, and breast reconstruction outcomes, including quality of life. FUNDING: Cancer Research UK, National Institute for Health Research

A clinical "near miss" highlights risk management issues surrounding ultrasound-guided and wire-localised breast resections.

BACKGROUND: The introduction of the National Health Service (NHS) Breast Screening Programme has led to a considerable increase in the detection of impalpable breast cancer. Patients with impalpable breast cancer typically undergo oncological resection facilitated either by the insertion of guide wires placed stereo-tactically or through ultra-sound guided skin markings to delineate the extent of a lesion. The need for radiological interventions on the day of surgery adds complexity and introduces the risk that a patient may accidentally transferred to the operating room directly without the image guidance procedure. CASE REPORT: A case is described of a patient who required a pre-operative ultrasound scan in order to localise an impalpable breast cancer but who was accidentally taken directly to the operating theatre (OR) and anaesthetised without pre-operative intervention. The radiologist was called to the OR and an on-table ultrasound was performed without further consequence. CONCLUSION: It is evident that breast cancer patients undergoing image-guided resection are exposed to an additional layer of clinical risks. These risks are not offset by the World Health Organisation surgical safety checklist in its present guise. Here, we review a number of simple and inexpensive changes to the system that may improve the safety of the breast cancer patient undergoing surgery

The impact of temporal variation in indocyanine green administration on tumor identification during fluorescence guided breast surgery.

BACKGROUND: On average, 21% of women in the USA treated with Breast Conserving Surgery (BCS) undergo a second operation because of close positive margins. Tumor identification with fluorescence imaging could improve positive margin rates through demarcating location, size, and invasiveness of tumors. We investigated the technique's diagnostic accuracy in detecting tumors during BCS using intravenous indocyanine green (ICG) and a custom-built fluorescence camera system. METHODS: In this single-center prospective clinical study, 40 recruited BCS patients were sub-categorized into two cohorts. In the first 'enhanced permeability and retention' (EPR) cohort, 0.25 mg/kg ICG was injected ~ 25 min prior to tumor excision, and in the second 'angiography' cohort, ~ 5 min prior to tumor excision. Subsequently, an in-house imaging system was used to image the tumor in situ prior to resection, ex vivo following resection, the resection bed, and during grossing in the histopathology laboratory to compare the technique's diagnostic accuracy between the cohorts. RESULTS: The two cohorts were matched in patient and tumor characteristics. The majority of patients had invasive ductal carcinoma with concomitant ductal carcinoma in situ. Tumor-to-background ratio (TBR) in the angiography cohort was superior to the EPR cohort (TBR = 3.18 ± 1.74 vs 2.10 ± 0.92 respectively, p = 0.023). Tumor detection reached sensitivity and specificity scores of 0.82 and 0.93 for the angiography cohort and 0.66 and 0.90 for the EPR cohort, respectively (p = 0.1051 and p = 0.9099). DISCUSSION: ICG administration timing during the angiography phase compared with the EPR phase improved TBR and diagnostic accuracy. Future work will focus on image pattern analysis and adaptation of the camera system to targeting fluorophores specific to breast cancer

Patient-level costs in margin re-excision for breast-conserving surgery

Background High rates of reoperation following breast‐conserving surgery (BCS) for positive margins are associated with costs to healthcare providers. The aim was to assess the quality of evidence on reported re‐excision costs and compare the direct patient‐level costs between patients undergoing successful BCS versus reoperations after BCS. Methods The study used data from women who had BCS with or without reoperation at a single institution between April 2015 and March 2016. A systematic review of health economic analysis in BCS was conducted and scored using the Quality of Health Economic Studies (QHES) instrument. Financial data were retrieved using the Patient‐Level Information and Costing Systems (PLICS) for patients. Exchange rates used were: US $1 = £0·75, £1 = €1·14 and US$1 = €0·85. Results The median QHES score was 47 (i.q.r. 32·5–79). Only two of nine studies scored in the upper QHES quartile (score at least 75). Costs of initial lumpectomy and reoperation were in the range US $1234–11786 and$655–9136 respectively. Over a 12‐month interval, 153 patients had definitive BCS and 59 patients underwent reoperation. The median cost of reoperations after BCS (59 patients) was £4511 (range 1752–18 019), representing an additional £2136 per patient compared with BCS without reoperation (P < 0·001). Conclusion The systematic review demonstrated variation in methodological approach to cost estimates and a paucity of high‐quality cost estimate studies for reoperations. Extrapolating local PLICS data to a national level suggests that getting BCS right first time could result in substantial savings

A ‘best practice’ care pathway improves management of mastitis and breast abscess

Background: As a result of surgical sub-specialisation, mastitis and breast abscess may be managed with unnecessary hospitalisation, prolonged admission, variable antibiotic prescribing, incision and drainage rather than aspiration, and loss to follow-up. Objective: To evaluate a ‘best-practice’ algorithm to improve management across a multi-site NHS Trust; focusing on uniformity of antibiotic prescribing, ultrasound assessment, admission rates, length of stay, intervention by aspiration or incision and drainage, and follow-up. Methods: Management was initially evaluated in a retrospective cohort (Phase-I: “PRE-pathway”, n=53) and subsequently compared to two prospective cohorts (Phase II and III = “POST-pathway”, n=141), one immediately following pathway introduction (Phase II n=61), and a further loop-closing audit (Phase-III, n=80) to assess sustainability of quality improvements. Results: The management pathway and referral proforma improved compliance with antibiotic guidelines (Pre=34.0% vs. Post=58.2%, p<0.01), which was maintained (Phase-II=54.1% vs. III=61.3%, p=0.68) and sustainably increased ultrasound assessment (Pre=37.7% vs. Post=77.3%, p<0.001; Phase-II=75.4% vs. III=78.8%, p=0.89). Reductions in rates of incision and drainage (Pre=7.5% vs. Post=0.7%, p<0.01) were maintained (Phase-II=0% vs. III=1.3%, p=0.38), and follow-up consistently improved (Pre=43.4% vs. Post=95.7%, p<0.001; Phase-II=91.8% vs. III=98.8%, p=0.12). Reduced hospital admission (Pre=30.2% vs. Post=20.6%, p=0.25) and median length of stay [Pre=2 days (range=1-5) vs. Post=1 day (range=1-6), p=0.07] were not statistically significant