The pharmacokinetics of intravenous (IV) vancomycin was studied in automated peritoneal dialysis (APD) patients who received a single IV dose of vancomycin (15 mg/kg total body weight). Dialysate samples were collected at the beginning, middle, and end of dwells 1 – 3 (on-cycler), and at the end of dwells 4 and 5 (off-cycler), for a 24-hour period. Blood samples were collected at the beginning, middle, and end of dwells 1 – 3 (on-cycler), and at the end of dwell 5 (off-cycler) for a 24-hr period. Pharmacokinetics parameters were calculated assuming a one-compartment model. Glomerular filtration rate (GFR) and vancomycin clearance (Cl) values were normalized to 1.73 m2. Ten patients [4 males, 6 females; 47.4 ± 9.9 years of age (mean ± SD)] who had received PD for a median 3.5 months (range 2 – 66 months) were studied. Dwell times were 2.3 ± 0.1 hours on cycler and 7.3 ± 0.1 hours off cycler. Vancomycin half-life was significantly different on-cycler than off-cycler (11.6 ± 5.2 hr vs 62.8 ± 33.0 hr; p < 0.001). Vancomycin total Cl (ClT) was 7.4 ± 2.0 mL/min. Renal Cl (ClR) and PD Cl (ClPD) accounted for 23.6% and 28.0% of ClT, respectively. ClR correlated with GFR (ClR = 0.90 GFR – 1.01; r2 = 0.79; p = 0.008). Mean vancomycin serum and dialysate end-of-dwell concentrations were above minimum inhibitory concentration of susceptible organisms (5 mg/mL) for the first cycler and the second ambulatory exchanges only. The results of this study suggest that, to provide adequate concentrations for susceptible organisms over a 24-hour period, current intermittent vancomycin dosing recommendations for PD-related peritonitis need to be changed to 35 mg/kg intraperitoneally on day 1, then 15 mg/kg IP thereafter ( i.e., once daily) in APD patients.

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Introduction: Current guidelines are for yearly mammograms in women with early-stage breast cancer. Among breast cancer survivors treated with lumpectomy, semi-annual compared to annual screening mammography of the ipsilateral breast has been associated with early detection of local recurrence. However, a potential harm of more frequent screening is false-positive breast biopsies that may lead to negative psychosocial effects and increased costs. Our objective was to investigate how frequency of screening mammograms affects rates of false-positive biopsy results and local recurrences among breast cancer survivors. Methods: We conducted a retrospective cohort study at Columbia University Medical Center (CUMC) in New York, NY of women diagnosed with stage 0-III breast cancer between 2007 and 2015, who were treated with lumpectomy and had at least 2 screening mammograms at CUMC within the first 3 years after diagnosis. Demographic and clinical information, including tumor characteristics and breast cancer treatments, were collected from the electronic health record. Frequency of mammography screening was defined as the median interval between 2 consecutive mammograms (every 6 months vs. yearly). Both false-positive biopsy results and local recurrences were identified by review of breast pathology reports. A false-positive biopsy was defined as a diagnostic breast biopsy without evidence of invasive or non-invasive cancer. Descriptive statistics and logistic regression models were conducted to examine relationships between covariates and either false-positive biopsy or local recurrence. Results: In our sample (n=1257), the median age at breast cancer diagnosis was 60 years (range, 24-93), including 47% non-Hispanic white, 14% non-Hispanic black, 31% Hispanic, and 7% Asian. Nearly 80% of women had semi-annual screening mammography of the ipsilateral breast during the first 3 years after breast cancer diagnosis. In univariate analysis, higher body mass index, more advanced stage disease, higher tumor grade, and receipt of chemotherapy, hormonal therapy, and radiation therapy were associated with more frequent screening. Comparing women who screened every 6 months vs. yearly, there was no difference in local recurrence rates (4.1% vs. 3.9%), including screen-detected or invasive/non-invasive breast cancer recurrences. In multivariable analysis, women who screened every 6 months compared to yearly had a greater than 2-fold increased risk of having a false-positive biopsy (OR: 2.40; 95% CI: 1.50-3.86). Also, younger age at diagnosis, higher tumor grade, and receipt of chemotherapy were associated with higher false positive rates, adjusting for covariates. Conclusions: We observed that women with early-stage breast cancer treated with lumpectomy who underwent semi-annual vs. annual screening mammography had more false-positive breast biopsies, but no difference in local recurrence rates. To date, there is no evidence that more frequent screening in breast cancer patients is associated with improved survival. Future studies are needed to determine optimal screening strategies for breast cancer survivors, including frequency of screening and use of supplemental breast imaging with ultrasound, MRI, or tomosynthesis. Citation Format: Yuan S, Manley HJ, Ha R, Yu A, Genkinger JM, Crew KD. Effect of mammography screening frequency on false-positive biopsy rates and detection of local recurrence among breast cancer survivors [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 PD2-15.