Synergistic activity of herbal extracts and antibiotics combinations against clinical strains of E. coli isolated from canine urinary infections

Poster Abstract

Staging Investigations in Asymptomatic Early Breast Cancer Patients at the Cancer Centre of Southeastern Ontario

Background: In 2012, the American Society for Clinical Oncology (ASCO) identified five key opportunities in oncology to improve patient care, recommending against imaging tests for the staging of patients with early breast cancer (EBC) at low risk for metastases. Similarly, the European Society of Medical Oncology (ESMO) guideline does not support radiological staging in asymptomatic EBC (aEBC). The purpose of this study was to assess local practice and outcomes of staging investigations (SIs) in aEBC at the Cancer Centre of Southeastern Ontario (CCSEO). Methods: A retrospective electronic and paper chart review was undertaken to identify all aEBC patients treated at our institution between January 2012 and December 2014. Patients with pathological staging of T1-T2 and N0-1 with any receptor status were included. We collected patient demographics, treatment and pathologic tumor characteristics. The use and outcomes of initial and follow-up SIs were recorded. Data were analyzed to determine associations between the use of SIs and clinical characteristics (chi-square tests, independent samples t-tests and Mann–Whitney U tests). Results: From 2012 to 2014, 295 asymptomatic EBC patients were identified. The mean age was 64, 81% were postmenopausal and 76% had breast conserving surgery. Stage distribution was as follows: stage I 42%, stage IIA 37% and stage IIB 21%. Receptor status was as follows: ER+ 84%, HER2+ 13% and triple negative 12%. Adjuvant chemotherapy was received by 36%, Trastuzumab by 10% and endocrine therapy by 76% of patients. Baseline SIs were performed in 168 patients (57%) for a total of 332 tests. Overt metastatic disease was found in five patients (one bone scan and four CT scans). Seventy-one out of the 168 patients (42%) who received initial staging imaging underwent 138 follow-up imaging tests, none of which were diagnostic for metastases. Nine patients with suspicious CT findings underwent biopsies, of which four were malignant (one metastatic breast cancer and three new primaries). Factors significantly associated with SI were as follows: younger age (p = 0.001), premenopausal status (p = 0.01), T2 stage (p < 0.001), N1 stage (p < 0.001), HER2 positive (p < 0.001), triple negative status (p = 0.007) and use of adjuvant chemotherapy (p < 0.001). Conclusions: Over a 3-year period at our institution, more than 50% of aEBC patients underwent a total of 470 initial and follow-up staging tests, yielding a cancer diagnosis (metastatic breast cancer or second primary cancer) in four patients. We, therefore, conclude that routine-staging investigations in aEBC patients have low diagnostic value, supporting current guidelines that recommend against the routine use of SI in this population

The effect of metformin vs placebo on sex hormones in CCTG MA.32.

BACKGROUND Metformin has been associated with lower breast cancer risk and improved outcomes in observational studies. Multiple biologic mechanisms have been proposed, including a recent report of altered sex hormones (SHs). We evaluated the effect of metformin on SHs in MA.32, a phase III trial of nondiabetic BC subjects randomized to metformin or placebo. METHODS We studied the subgroup of post-menopausal hormone receptor negative BC subjects not receiving endocrine treatment who provided fasting blood at baseline and at 6 months after randomization. Sex hormone binding globulin (SHBG), bioavailable testosterone (BT) and estradiol levels were assayed using ECLIA (electrochemiluminescense immunoassay). Change from baseline to 6 months between study arms was compared using Wilcoxon sum rank tests and regression models. RESULTS 312 women were eligible (141 metformin vs 171 placebo); the majority of subjects in each arm had T1/2, N0, HER2 negative BC and had received (neo)adjuvant chemotherapy. Mean age ± SD was 58.1±6.9 vs 57.5±7.9 years, mean BMI was 27.3±5.2 vs 28.9±6.4 kg/m2 for metformin vs placebo respectively. Median estradiol decreased between baseline and 6 months on metformin vs placebo (-5.7 vs 0 pmol/L; p < 0.001) in univariable analysis and after controlling for baseline BMI and BMI change (p < 0.001). There was no change in SHBG or BT. CONCLUSION Metformin lowered estradiol levels, independent of BMI. This observation suggests a new metformin effect that has potential relevance to estrogen sensitive cancers

Additional file 1: Table S1A. of A phase-I study of lapatinib in combination with foretinib, a c-MET, AXL and vascular endothelial growth factor receptor inhibitor, in human epidermal growth factor receptor 2 (HER-2)-positive metastatic breast cancer

Pharmacokinetics of lapatinib. Table S1B. Pharmacokinetics of foretinib. (DOCX 558 kb

First-line nivolumab plus ipilimumab in advanced non-small-cell lung cancer (CheckMate 568) : Outcomes by programmed death ligand 1 and tumor mutational burden as biomarkers

PURPOSE CheckMate 568 is an open-label phase II trial that evaluated the efficacy and safety of nivolumab plus low-dose ipilimumab as first-line treatment of advanced/metastatic non-small-cell lung cancer (NSCLC). We assessed the association of efficacy with programmed death ligand 1 (PD-L1) expression and tumor mutational burden (TMB). PATIENTS AND METHODS Two hundred eighty-eight patients with previously untreated, recurrent stage IIIB/IV NSCLC received nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks. The primary end point was objective response rate (ORR) in patients with 1% or more and less than 1% tumor PD-L1 expression. Efficacy on the basis of TMB (FoundationOne CDx assay) was a secondary end point. RESULTS Of treated patients with tumor available for testing, 252 patients (88%) of 288 were evaluable for PD-L1 expression and 98 patients (82%) of 120 for TMB. ORR was 30% overall and 41% and 15% in patients with 1% or greater and less than 1% tumor PD-L1 expression, respectively. ORR increased with higher TMB, plateauing at 10 or more mutations/megabase (mut/Mb). Regardless of PD-L1 expression, ORRs were higher in patients with TMB of 10 or more mut/Mb (n = 48: PD-L1, ≥ 1%, 48%; PD-L1, < 1%, 47%) versus TMB of fewer than 10 mut/Mb (n = 50: PD-L1, ≥ 1%, 18%; PD-L1, < 1%, 5%), and progression-free survival was longer in patients with TMB of 10 or more mut/Mb versus TMB of fewer than 10 mut/Mb (median, 7.1 v 2.6 months). Grade 3 to 4 treatment-related adverse events occurred in 29% of patients. CONCLUSION Nivolumab plus low-dose ipilimumab was effective and tolerable as a first-line treatment of advanced/metastatic NSCLC. TMB of 10 or more mut/Mb was associated with improved response and prolonged progression-free survival in both tumor PD-L1 expression 1% or greater and less than 1% subgroups and was thus identified as a potentially relevant cutoff in the assessment of TMB as a biomarker for first-line nivolumab plus ipilimumab.</p