Non-Animal Stabilized Hyaluronic Acid (NASHA) Gel Marker vs. Surgical Clips for Tumor Bed Delineation in Breast Cancer Using MR-Simulation

Abstract

Consistent delineation of the tumor bed (TB) after breast conserving surgery (BCS) is critical and remains a challenge with increasing prevalence of oncoplastic surgeries. Clips are generally used to help TB identification on CT-simulation but they are not well identified on MR-simulation. The aim of this study is to assess whether the use of NASHA gel with MR-simulation yields similar interobserver variability (inter-OV) compared to clips with CT-simulation. This prospective single arm feasibility study included patients eligible for BCS. After lumpectomy, the surgeon placed both clips (>5) and NASHA gel drops as markers to define the TB. Patients underwent CT and MRI simulation scans. Five radiation oncologists and one radiologist delineated the TB aided by clips on CT, and gel on MRI. The observers also assessed the visibility and utility of the gel (scale from 1 to 10), as well as the cavity visualization score (CVS, scale from 1 to 5). The primary endpoint was the inter-OV of the delineated TB using the overlap difference of contours using clips and CT versus gel and MRI, with the conformity index measured according to the pair definition of the Dice Similarity Coefficient (DSC). Of the 35 patients recruited, 30 were eligible for inter-OV analysis of TB delineation and 5 patients required further breast surgery for positive margins. One third of the eligible patients underwent an oncoplastic procedure. There were no significant differences between inter-OV of delineated TB using clips and CT versus gel and T2-weighted MRI with the mean DSC (0.60 vs 0.62, p = 0.364). The observers reported higher usefulness of gel in patients with an oncoplastic procedure than not (median US 8.2 vs 6.6, p = 0.024), and higher visibility of gel in patients who had their scans within 6 weeks than beyond post-op (median VS 8.1 vs 6.1, p = 0.013). When the CVS was higher (3-5), the median US of gel was lower (5.9 vs 7.8, p = 0.004), and the conformity index of clip and CT delineated TB was higher (median DSC 0.72 vs 0.53, p <0.001). Interestingly, a higher CVS did not lead to significantly higher conformity index of gel and T2-weighted MR delineated TB (mean DSC 0.67 vs 0.58, p = 0.073). NASHA gel injection added a median of 3 minutes to the operating theatre (OT) time and was rated as 'easy' in 89% of cases by surgeons. There were no immediate adverse events (AE) in OT, while 2 of 35 patients later experienced a grade 3 AE - hematoma which required evacuation in OT day 1 post-BCS, and infected seroma which required drainage and washout in OT 2 months post-BCS and axillary dissection. These reflect common risks with standard BCS and are not clearly attributed to gel injection alone. Use of NASHA gel leads to similar inter-OV of BC TB delineation compared to >5 clips. NASHA gel is hence a reliable alternative to clips when MR-simulation is used.