Abstract Background There is growing evidence that circulating tumor cells (CTCs) have prognostic impact in patients (pts) with early breast cancer (EBC). In this study the persistence of CTCs immediately after and two years after chemotherapy (Ctx) was prospectively evaluated according to molecular subtypes within the German multicentre SUCCESS trials. Methods SUCCESS A and C were randomized Phase III studies including pts with node positive or high-risk node negative EBC. In each trial two different adjuvant Ctx regimen were compared: FEC-DOC (3 cycles of FEC followed by 3 cycles of Docetaxel) to FEC-DG (3 cycles of FEC followed by 3 cycles of Docetaxel/Gemcitabine) in SUCCESS A and in the SUCCESS C study FEC-DOC to an anthracycline-free Ctx regimen (6 cycles of Docetaxel/Cyclophosphamide). Both studies involved a second randomization after Ctx: 2 vs. 5 years of zoledronic acid treatment (SUCCESS A) or 2-years of an individualized lifestyle-intervention program vs. general lifestyle recommendations (SUCCESS C). Adequate endocrine treatment and treatment with trastuzumab as indicated were included in both trials. As part of the translational research program, 23ml of peripheral blood were drawn to isolate CTCs using the CellSearch System (Veridex, USA). After immunomagnetic enrichment with an anti-EpCam-antibody, cells were labelled with anti-CK8/18/19 and anti-CD45 antibodies to distinguish epithelial cells from leucocytes. The cut-off for CTC-positivity was ≥ 1 CTC. Molecular subtypes were defined as luminal-A-like (hormone-receptor positive, G1 or 2), luminal-B-like (hormone-receptor positive, G3), HER2-positive and triple-negative. Results CTC analyses were performed for 3344 blood samples collected immediately after Ctx and for 1352 blood samples two years after Ctx. After Ctx 17.5% (584/3344) of the pts were CTC-positive (range 1 – 124 CTCs), and two years after Ctx the positivity rate for CTCs was 17.2% (233/1352, range 1-99). CTC positivity as assessed immediately after Ctx differed significantly among molecular subtypes (chi-square test, p < 0.001): Pts with HER2-positive tumors were more likely to have CTCs in the blood (26.3%, 105/400) as compared to pts with luminal-A-like tumors (15.4%, 283/1842), luminal-B-like tumors (17.7%, 142/802), or triple-negative tumors (18.0%, 54/300). Two years after Ctx CTC-positivity did not differ significantly among molecular subtypes (chi-square test, p = 0.463). CTC-positivity rates were 15.7% (96/613) for luminal-A-like tumors, 19.1% (49/256) for luminal-B-like tumors, 17.2% (51/296) for HER2-positive tumors, and 19.8% (37/187) for triple-negative tumors. Conclusions The data of this study confirm previous findings that CTCs may persist after standard adjuvant therapy. Immediately after Ctx CTCs seem to be more frequent in pts with HER2-positive tumors as compared to other molecular subtypes, while two years after Ctx no differences in CTC positivity among molecular subtypes were detected. These results might indicate good efficacy of HER2-targeted therapies on CTCs. Citation Format: Bernadette AS Jaeger, Ulrich Andergassen, Julia K Neugebauer, Marianna Alunni-Fabbroni, Carola A Melcher, Carsten Hagenbeck, Susanne Albrecht, Ralf Lorenz, Thomas Decker, Georg Heinrich, Tanja Fehm, Andreas Schneeweiss, Matthias W Beckmann, Klaus Pantel, Klaus Friese, Peter A Fasching, Thomas WP Friedl, Wolfgang Janni, Brigitte K Rack. Persistence of circulating tumor cells immediately after and two years after systemic adjuvant chemotherapy in patients with early breast cancer – Results of the German SUCCESS trials [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P4-01-08.
Introduction: Prosthetic vascular graft infection is a rare but severe complication in reconstructive vascular surgery and is associated with high morbidity and mortality. Early diagnosis may reduce complications and duration of hospitalisation. For diagnosis, imaging devices such as US, CT and MRI are widely available. However, morphological imaging techniques are lacking differentiation between active infection and reparative tissue. Our objective is to evaluate the potential of 18F-FDG PET/CT for diagnosis of prosthetic vascular graft infection after surgery using prosthetic grafts especially with synthetic prosthesis.
Abstract Purpose To study the occurrence of severe visual impairment ( SVI ) and treatment outcome at 12 months in patients treated for wet age‐related macular degeneration (AMD) by use of data from the Swedish Macula Register (SMR) and referrals to the regional low vision clinics in five northern counties. Methods Referrals to low vision clinics during 2005, 2009 and 2013 and treatment outcome at 12 months from the SMR database from 2008 until 2013 in patients >65 years of age in five northern counties were included in the survey. Results The rate of referral due to AMD was significantly reduced during the time period (−48%; p < 0.001). At 12 months, a significant slight mean improvement in log MAR visual acuity (VA) was observed (−0.01, SD 0.37; p < 0.001) after a mean of 5.0 ± 2.3 anti‐vascular endothelial growth factor (VEGF)‐injections were administered. Age and low baseline VA was associated with less favourable visual outcome (p < 0.001). Conclusion Referral rate to low vision clinic is a valuable tool for estimating occurrence of SVI and fell between the years 2005 until 2013. Data from the SMR showed improvement in visual acuity on the whole, but also identified patients at high risk for developing SVI during anti‐ VEGF ‐treatment.
1010 Background: Gemcitabine (G) has shown to have a relevant single agent efficacy and to improve chemotherapy response to taxanes in advanced BC patients. Aim of this study was to evaluate the effect of G on disease free survival (DFS) in high risk adjuvant BC patients. Methods: This is a phase III, randomized, open label trial of FEC-Doc vs. FEC-DocG (3 cycles of FEC (500/100/500 mg/m²) followed by 3 cycles of docetaxel (Doc; 100mg/mg²) every three weeks (q3w) vs. 3 cycles of FEC followed by 3 cycles of G (1,000 mg/m² d1,8) and Doc (75 mg/m²) q3w). Key inclusion criteria: stage N1 or T2–T4 or grade 3 or age ≤ 35 or hormone receptor (ER/PR) negative. Key exclusion criteria: locally recurrent/metastatic disease; prior systemic therapy or radiotherapy for current BC. Strata for randomization: nodal, ER/PR, menopausal and HER2 status and grading. Primary and secondary study aims were DFS and overall survival (OS). Survival rates were estimated by the Kaplan-Meier method. Cox regression models were fitted to estimate unadjusted hazard ratios (HRs). Further exploratory analyses investigated treatment differences within patient subgroups. Results: 3,754 patients were randomized to FEC-Doc (n=1898) or FEC-DocG (n=1856). Median observation time was 5.3 ys with 456 (238 vs. 218; FEC-Doc vs. FEC-DocG) events for DFS and 269 (140 vs. 129) events for OS. Mean age was 53.5 ys and 58.7% were ≥ T2, 66.1% were nodal positive, 29.3% ER and PR negative and 23.5% HER2 positive. 5-year DFS rate was 0.87 for both randomization arms and 5-year OS was 0.93 for both arms. HRs for DFS and OS were 0.93 (95%CI: 0.78-1.12; p=0.46) and 0.94 (95%CI: 0.74-1.19; p=0.60). Further analyses, accounting for age, body mass index, tumour stage, grading, lymph node status, tumor type, hormone receptor and HER2neu status, did not generate any hypothesis for subgroup-specific efficacy. Conclusions: AdjuvantGemcitabine does not improve the efficacy of FEC-Doc chemotherapy for high risk breast cancer patients. With regard to the risk-benefit ratio, we do not recommend adjuvant Gemcitabine for the adjuvant treatment of high risk breast cancer patients. Future analyses will report on circulating tumor cells, serum markers and pharmacogenomics. Clinical trial information: 2005-000490-21.
