Citations

Background: Texturing of breast implants is done to decrease the risk of associated complications. Each manufacturer utilizes unique and at times proprietary techniques to texture the surface of their implants. Little is known about the integrity of this surface structure texturing or the propensity for the surfaces to shed particulate matter. This study aimed to determine the extent of surface particulate shedding from 3 textured implants approved by the US Food and Drug Administration (FDA), which are manufactured by Allergan, Mentor, and Sientra. Methods: Control images of each of the 3 textured breast implants were obtained with scanning electron microscopy (SEM). A liquid adhesive, ethylene vinyl acetate (EVA) copolymer was then applied to the external shell of the implants, allowed to cool, and peeled from the surface. Images of the EVA copolymer were taken with SEM to qualitatively analyze displacement of surface particulate debris. Scanning electron microscopy imaging of the implants was repeated for qualitative comparisons with the control images. Results: The peeled copolymer of the 3 implants exhibited surface shedding. Comparison of the 3 breast implants showed the shedding to be greatest for the Allergan implant. Conclusions: This study highlights the dynamic surface material properties of the 3 FDA-approved breast implants. Shedding of particulate matter from the implant surfaces can be precipitated by moderate adhesion. Our qualitative examination of SEM findings showed more debris shed from the Allergan breast implants than from the Mentor or Sientra implants.

To increase the efficiency and effectiveness of clinical research studies, cerebral palsy (CP) specific Common Data Elements (CDEs) were developed through a partnership between the National Institute of Neurological Disorders and Stroke (NINDS) and the American Academy of Cerebral Palsy and Developmental Medicine (AACPDM). International experts reviewed existing NINDS CDEs and tools used in studies of children and young people with CP. CDEs were compiled, subjected to internal review, and posted online for external public comment in September 2016. Guided by the International Classification of Functioning, Disability and Health framework, CDEs were categorized into six domains: (1) participant characteristics; (2) health, growth, and genetics; (3) neuroimaging; (4) neuromotor skills and functional assessments; (5) neurocognitive, social, and emotional assessments; and (6) engagement and quality of life. Version 1.0 of the NINDS/AACPDM CDEs for CP is publicly available on the NINDS CDE and AACPDM websites. Global use of CDEs for CP will standardize data collection, improve data quality, and facilitate comparisons across studies. Ongoing collaboration with international colleagues, industry, and people with CP and their families will provide meaningful feedback and updates as additional evidence is obtained. These CDEs are recommended for NINDS‐funded research for CP.What this paper adds This is the first comprehensive Common Data Elements (CDEs) for children and young people with CP for clinical research. The CDEs for children and young people with CP include common definitions, the standardization of case report forms, and measures. The CDE guides the standardization for data collection and outcome evaluation in all types of studies with children and young people with CP. The CDE ultimately improves data quality and data sharing.

5 Background: Triple-negative breast cancer (TNBC) is an immunogenic breast cancer subtype, with a greater percentage of tumors containing tumor-infiltrating lymphocytes (TILs) compared to non-TNBC. TILs are prognostic for recurrence and predictive for chemotherapy benefit in TNBC, but not in estrogen receptor (ER)-positive tumors. A subset of TNBC expresses the androgen receptor (AR), and resembles ER-positive breast cancer in terms of demographics (older age) and clinical course (later recurrences that tend to involve bone). However, little is known regarding the association between TILs and AR expression in TNBC. Methods: From a cohort of 9982 women with surgically-treated non-metastatic breast cancer, patients who met criteria for TNBC (ER/PR < 1% and HER2-negative) by centralized-pathology review were included as previously published [Leon-Ferre et al, Breast Cancer Res Treat 2017]. Stromal TILs in these tumors were quantified on full-face hematoxylin and eosin sections from the surgical specimen, following the 2014 TIL Working Group recommendations [Salgado et al, Ann Oncol 2014]. The expression of AR [EPR1535(2), Abcam] was scored as a continuous variable (1% increments), and categorized as absent (0%), low (1-25% ), low-moderate (26-50%) moderate (51-75%) and high (> 75%) and correlated with TIL density. Results: 605 patients met criteria for TNBC. The median age was 56 years. Most tumors were T1-2 (95%), N0-1 (86%), and high grade (88%). The median stromal TIL content was 20% (0-90%). Tumor tissue was available for AR staining in 509/605 patients. 165 (32%) tumors expressed AR as follows: low: 12%, low-moderate: 7%, moderate: 5%, and high: 8%. Apocrine tumors (n = 30) expressed AR most frequently (86%) and at higher levels (AR high: 50%). For all 509 tumors, the median stromal TIL content according to AR expression was AR absent: 20%, AR low: 20%, AR low-moderate: 15%, AR high: 10%. AR and stromal TILs (both as continuous variables) demonstrated a weak inverse correlation (correlation coefficient -0.1064, p = 0.017). Conclusions: AR expression in TNBC is associated with lower levels of stromal TILs. Additional data correlating the AR, stromal TILs and outcomes in this cohort will be presented at the meeting.

An analysis of the cement mantle obtained with the Exeter impaction allografting system at one centre showed that it was either deficient or absent in almost 47% of Gruen zones. We therefore examined the mantle obtained using this system at another hospital and compared the results with those from the CPT and Harris Precoat Systems at other centres. The surgical indications for the procedure and the patient details were broadly similar in all four hospitals. There was some variation in the frequency of use of cortical strut allografts, cerclage wires and wire mesh to supplement the impaction allograft. Analysis of the cement mantles showed that when uncertain Gruen zones were excluded, the incidence of zones with areas of absence or deficiency of the cement was 47% and 50%, respectively, for the two centres using the Exeter system, 21% for the CPT system and 18% for the Harris Precoat system. We measured the difference in size between the proximal allograft impactors and the definitive prosthesis for each system. The Exeter system impactors are shorter than the definitive prosthesis and taper sharply so that the cavity created is inadequate, especially distally. The CPT proximal impactors are considerably longer than the definitive prosthesis and are designed to give a mantle of approximately 2 mm medially and laterally and 1.5 mm anteriorly and posteriorly. The Harris Precoat proximal impactors allow for a mantle with a circumference of 0.75 mm in the smaller sizes and 1 mm in the larger. Many reports link the longevity of a cemented implant to the adequacy of the cement mantle. For this reason, femoral impaction systems require careful design to achieve a cement mantle which is uninterrupted in its length and adequate in its thickness. Our results suggest that some current systems require modification.

Abstract Background: While TNBC remains the most aggressive type of breast cancer (BC), substantial heterogeneity in biology and outcomes exists among TNBC subtypes. Historically, risk stratification of TNBC has been based on anatomic factors such as tumor size, nodal involvement and presence of distant metastases. However, these features alone fail to accurately predict outcomes. Tumor immune infiltration (sTILs) and distribution of immune cell subsets in the perip heral blood (NLR) have emerged as variables reported to be associated with outcomes in TNBC. We sought to evaluate whether NLR and sTILs provided independent prognostic information in TNBC. Methods: From a cohort of 9,982 women who underwent BC surgery at Mayo Clinic, Rochester, MN between Jan 1985 and Dec 2012, we identified 605 centrally-confirmed TNBC tumors. Patients (pts) with prior BC, bilateral BC, non-invasive disease, stage IV, neoadjuvant therapy, endocrine therapy, or adenoid cystic histology were excluded. For eligible tumors, clinical and pathologic variables were evaluated, including peripheral blood NLR and central assessment of sTILs per the 2014 International TILs Working Group recommendations. We calculated the Pearson correlation coefficient (PCC) between NLR and sTILs and constructed Cox Proportional Hazards Models to evaluate their association with invasive-disease free (IDFS) and overall survival (OS). NLR and sTILs were both analyzed as continuous variables. Results: Most pts had T1-2 (95%) and N0-1 disease (86%). Median OS follow-up was 10.6yrs. Median IDFS was 12yrs (95%CI 10.2-16.7) and median OS was 18.8yrs (95%CI 15.6-20.8). NLR and sTILs were available in 408 and 599 pts, respectively. The median NLR and sTIL content were 2.29 (0.14-10.50) and 20% (0-90%), respectively. NLR and sTILs were poorly correlated (PCC 0.0237). On univariate analysis (UVA), a higher NLR was associated with worse IDFS (HR 1.13; 95%CI 1.02-1.26, p=0.02) and OS (HR 1.17; 95%CI 1.04-1.31, p=0.01). Each 1% increment in sTILs was associated with improved IDFS (HR 0.99; 95%CI 0.98-0.99, p&lt;0.001) and OS (HR 0.99, 95%CI 0.98-1.00, p&lt;0.001). Among pts with high sTILs (≥20%), a higher NLR remained significantly associated with worse IDFS (HR 1.21; 95%CI 1.05-1.38, p=0.007) and OS (HR 1.25; 95%CI 1.09-1.44, p=0.001). In contrast, among pts with low sTILs (&lt;20%), NLR was not associated with IDFS (HR 1.07; 95%CI 0.89-1.28, p=0.49) or OS (HR 1.07; 95%CI 0.88-1.30, p=0.49). The interaction test between NLR and sTILs did not reach statistical significance. A multivariate analysis (MVA; including age, menopausal status, histologic subtype, grade, tumor size, nodal stage, Ki-67, NLR, sTILs, adjuvant chemotherapy, type of surgery and adjuvant radiation) showed that sTILs remained independently associated with IDFS (HR 0.99, 95%CI 0.97-1.0, p=0.019) and OS (HR 0.99, 95% CI 0.97-1.0, p=0.044), whereas NLR did not. Conclusions: A lower NLR and a higher sTIL content were each associated with improved IDFS and OS among pts with nonmetastatic TNBC on UVA. However, when evaluated on a MVA, only sTILs remained independently associated with IDFS and OS. Our data suggest that the effect of sTILs on outcomes may not be modified by the NLR. Citation Format: Leon-Ferre RA, Polley M-Y, Liu H, Gilbert J, Cafourek V, Hillman D, Negron V, Boughey JC, Liu MC, Ingle JN, Kalari K, Couch FJ, Visscher DW, Goetz MP. Prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and its relation to stromal tumor infiltrating lymphocytes (sTILs) in triple negative breast cancer (TNBC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-05-06.

AbstractWe performed analyses of the randomized phase 3 ASPIRE and ENDEAVOR trials to investigate the efficacy of carfilzomib among subgroups of relapsed or refractory multiple myeloma patients who had early or late disease relapse following initiation of the immediately prior therapy. In ASPIRE and ENDEAVOR, patients had received 1 to 3 prior lines of therapy. Patients in ASPIRE received carfilzomib, lenalidomide, and dexamethasone (KRd) or lenalidomide and dexamethasone (Rd), and patients in ENDEAVOR received carfilzomib and dexamethasone (Kd) or bortezomib and dexamethasone (Vd). Patients with relapse ≤1 year after initiating the most recent prior line of therapy were categorized as early relapsers, and patients with relapse after >1 year were categorized as late relapsers. The median progression‐free survival (PFS) in ASPIRE for early relapsers was 21.4 months for KRd vs 10.7 months for Rd (hazard ratio [HR]: 0.714; 95% confidence interval [CI]: 0.508–1.004; P = 0.0257), and for late relapsers was 29.7 months for KRd vs 18.2 months for Rd (HR: 0.675; 95% CI: 0.533–0.854; P = 0.0005). The overall response rate (ORR) for early relapsers was 83.2% for KRd vs 54.8% for Rd, and for late relapsers was 89.0% for KRd vs 69.7% for Rd. The median PFS in ENDEAVOR (Kd vs Vd) for early relapsers was 13.9 months vs 5.7 months (HR: 0.598; 95% CI: 0.423–0.846; P = 0.0017), and for late relapsers was 22.2 months vs 10.2 months (HR: 0.486; 95% CI: 0.382–0.620; P < 0.0001). The ORR (Kd vs Vd) for early relapsers was 63.4% vs 49.1% and for late relapsers was 81.8% vs 66.8%. In conclusion, patients with relapsed or refractory multiple myeloma who received carfilzomib‐containing regimens had improved PFS and ORR compared with control groups, regardless of whether they had an early or late relapse following the most recent prior therapy.