Phenotypic diversity of circulating tumour cells in patients with metastatic castration‐resistant prostate cancer

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/139087/1/bju13631_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/139087/2/bju13631.pd

First trimester neutrophil to lymphocyte ratio (NLR) and pregnancy outcome

In early pregnancy, miscarriage is the most common complication. The early identification of women at high risk for miscarriage could improve pregnancy outcomes. We investigated whether the first trimester neutrophil to lymphocyte ratio (NLR) could be used as a prognostic marker for miscarriage, in pregnancies after spontaneous conception. We retrospectively identified 129 pregnant women who had a first trimester full blood count available and known pregnancy outcome. First trimester NLR was calculated for each woman and mean NLR values were compared between women with live births (group 1) with those with miscarriage (group 2). Mean NLR values were not significantly different between the two groups (2.5 ± 1.0 vs. 2.9 ± 1.5, p = .167) and were not associated with pregnancy outcomes. However, NLR values >5.8 were exclusively observed in the miscarriage group (p = .028).IMPACT STATEMENT What is already known on this subject? As a marker of inflammation, NLR has been found to be elevated in various diseases and complications that affect pregnancy outcome. Pregnancy complications, such as preeclampsia and gestational diabetes have been associated with an increased NLR, but little is known on their direct causal relationship. So far, there has been no evaluation of maternal NLR in regards to miscarriage in otherwise healthy women. What do the results of the study add? We found that NLR does not differ significantly between pregnant women with live birth and those whose pregnancy ended in miscarriage . However, NLR values >5.8 were solely found in the miscarriage group- an observation that was statistically significant. What are the implications of these findings for clinical practice and/or further research? The above finding supports high NLR values as a potential marker for the identification of the subset of miscarriages in otherwise healthy pregnant women. This may allow personalised approaches to prevent pregnancy loss

Real-World Data on Treatment Management and Outcomes of Patients with Newly Diagnosed Advanced Epithelial Ovarian Cancer in Greece (The EpOCa Study)

New treatment modalities have been recently introduced in the management of ovarian cancer (OC). Herein, we sought to investigate their implementation in routine clinical practice and examine the real-world management of OC in Greece. EpOCa was a non-interventional, multicenter, retrospective study in patients with advanced epithelial OC. The primary outcome was to estimate the proportions of the different treatment regimens used per line of therapy, while progression-free survival (PFS) and overall survival (OS) were the key secondary endpoints. A total of 154 patients were enrolled in the study, among whom, 40% were tested for BRCA mutations and 30% were found to be positive. Nearly 90% of patients underwent debulking surgery at diagnosis, with few operations being also recorded upon relapse. Platinum-based chemotherapy (CT) was predominantly used in the first line with half of patients also receiving angiogenesis inhibitor (AI), while non-platinum-based CT was preferred in later lines. The median PFS was 18.2 and 8.8 months in the first- and second-line setting, respectively, whereas the median OS was approximately 50 months. Our study adds to the available, but limited, real world data on the management of ovarian cancer providing evidence regarding the applied treatment strategies and outcomes of patients in Greece

Prognostic Role of Circulating Tumor Cells in Patients with Metastatic Castration-Resistant Prostate Cancer Receiving Cabazitaxel: A Prospective Biomarker Study

Rational: Circulating tumor cells (CTCs) appear to be a promising tool for predicting the clinical outcome and monitoring the response to treatment in patients with solid tumors. The current study assessed the clinical relevance of monitoring CTCs in patients with metastatic castration resistant prostate cancer (mCRPC) treated with cabazitaxel. Patients and Methods: Patients with histologically confirmed mCRPC who were previously treated with a docetaxel-containing regimen and experienced disease progression were enrolled in this multicenter prospective study. CTC counts were enumerated using the CellSearch system at baseline (before cabazitaxel initiation), after one cabazitaxel cycle (post 1st cycle) and at disease progression (PD). Patients were stratified into predetermined CTC-positive and CTC-negative groups. The phenotypic characterization was performed using double immunofluorescence staining with anti-CKs and anti-Ki67, anti-M30 or anti-vimentin antibodies. Results: The median PFS and OS were 4.0 (range, 1.0–17.9) and 14.5 (range, 1.2–33.9) months, respectively. At baseline, 48 out of 57 (84.2%) patients had ≥1 CTCs/7.5 mL of peripheral blood (PB) and 37 (64.9%) had ≥5 CTCs/7.5 mL of PB. After one treatment cycle, 30 (75%) out of the 40 patients with available measurements had ≥1 detectable CTC/7.5 mL of PB and 24 (60%) ≥ 5CTCs/7.5 mL of PB; 12.5% of the patients with detectable CTCs at the baseline sample had no detectable CTCs after one treatment cycle. The detection of ≥5CTCs/7.5 mL of PB at baseline and post-cycle 1 was associated with shorter PFS and OS (p = 0.002), whereas a positive CTC status post-cycle 1 strongly correlated with poorer OS irrespective of the CTC cut-off used. Multivariate analysis revealed that the detection of non-apoptotic (CK+/M30−) CTCs at baseline is an independent predictor of shorter OS (p = 0.005). Conclusions: In patients with mCRPC treated with cabazitaxel, CTC counts both at baseline and after the first cycle retain their prognostic significance, implying that liquid biopsy monitoring might serve as a valuable tool for predicting treatment efficacy and survival outcomes

Circulating tumor cell (CTC) rise and outcome in patients with metastatic castration-resistant prostate cancer (mCRPC) with low baseline CTC counts.

Background: CTCs are prognostic in CRPC. Baseline (BL) CTC < 5 CTCs/7.5mL are associated with improved prognosis. We have previously shown that a post-treatment 30% decline in CTC is associated with improved survival (OS) in patients with high (≥5) BL CTCs. We investigated the value of a rise in CTCs during the first 12-weeks (wks) of treatment in the COU-AA-301 (abiraterone) and IMMC-38 (chemotherapy) trial datasets in patients with low (<5) baseline CTC counts. Methods: CTC of patients (pts) were determined using the CELLSEARCH (Janssen Diagnostics, LLC) platform. Pts with BL CTCs <5, and CTCs at 4, 8 or 12 weeks were evaluated. CTC progression (CTCrise) was defined as any increase in CTCs relative to BL at any of the 3 timepoints (4,8,12 wks). Landmark survival analyses at 12 wks were performed. Association of CTCrise with OS was evaluated with Cox regression in multivariable (MV) analysis (ECOG, LDH, ALP, Alb, Hb, BL CTC and PSA as covariates). Logistic regression was used to evaluate association with PSA response. Results: 509 pts (419 in COU-301 and 90 in IMMC38) were identified as having a BL CTC<5; BL CTC was 0 in 257 pts (50.7%). Overall, median OS was 21.9m (95%CI:20.6-23.3). 212 pts (41.7%) experienced a CTCrise within 12-weeks of starting treatment; of these, 117 (55%) had a CTCrise as early as 4 weeks post-treatment. OS was significantly reduced (27.1 vs 15.2 months; HR: 3.5; 95%CI 2.6-4.7) in patients with a CTCrise in these first 12-weeks. Both BL CTC (log-transformed) and CTCrise were independently associated with OS in the MV survival model. Furthermore, a PSA rise of ≥25% from baseline at 12 wks was more frequent in pts with a CTC rise vs. no rise (46.9% vs 14%, p<0.001) Conclusions: BL CTC and CTC rises are independently associated with OS in CRPC pts with low (<5) BLCTC treated with abiraterone and chemotherapy. These findings will require prospective validatio