Development of a new outcome-prediction model for patients with urothelial carcinoma of the bladder prior to cystectomy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 360-360
Author(s):  
Mario W. Kramer ◽  
Christoph A. J. von Klot ◽  
Annika Heinisch ◽  
Gerd Wegener ◽  
Mahmoud Abbas ◽  
...  

360 Background: Prognostic models for patients undergoing cystectomy are spares and mostly rely on histopathological parameters. The present study investigated clinical prognostic indicators that are available prior to cystectomy for developing a risk stratification model. Methods: Charts were reviewed from 279 bladder cancer patients that were treated with radical cystectomy and bilateral lymphadenectomy. Of those 194 were eligible for study entry due to availability of necessary data. None of the patients had neoadjuvant therapy. Various preoperative parameters were analyzed and optimum cut-off points were identified using ROC curves. A risk stratification model was developed based on multivariate analysis. Analyzed factors included serum-creatinine, hemoglobin, white blood cells, C - reactive protein (CRP), age, gender, and body mass index. Results: In multivariate analysis, preoperative serum-creatinine (>93 umol/l), white blood cells (>10.2 tsd/ul), CRP (>3 mg/l) and BMI (<18,5 kg/m2 or ≥30 kg/m2) were independent predictor of poor cancer-specific survival (CSS). A new scoring model was developed, consisting of those four parameters. The stratification model showed significant differences based on Kaplan-Meier analysis for the whole cohort as well as for subgroup analysis (pT2-4, Nx, M0) (p<0.001). CSS after 36 (60) months for low, intermediate and high risk group was 82.6% (76.2%), 37.7% (30.9%) and 22.2% (16.7%), respectively (p<0.0001). Conclusions: Our scoring model based on preoperative clinical parameters can discriminate bladder cancer patients prior to cystectomy in respect of CSS. This might help physicians to recommend treatment options such as neoadjuvant therapy. The scoring model needs external validation considering prospective study design and discriminating patients who received neoadjuvant chemotherapy.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 353-353
Author(s):  
Terence W. Friedlander ◽  
David Lu ◽  
Rachel Krupa ◽  
Gayatri Premasekharan ◽  
Christopher J. Welty ◽  
...  

353 Background: Muscle invasive(MIBC) and metastatic (mBCa) bladder cancer patients have few options to extend survival. Recent studies have shown that PD-1 and programmed death-ligand 1 (PD-L1) checkpoint inhibitors have activity even in chemotherapy refractory patients and it has been proposed that PD-L1 expression on tumors or lymphocytes may correlate with response to therapy. To identify potential patients who may benefit from PD-1/PD-L1 targeted immunotherapeutics, we utilized a non-invasive, real-time blood test for PD-L1 protein expression in circulating tumor cells (CTCs) and white blood cells (WBCs) of bladder cancer patients. Methods: Twelve blood samples from unique patients with MIBC or mBCa were collected and shipped to Epic Sciences. All nucleated cells were plated onto glass slides and subjected to IF staining and CTC identification by fluorescent scanners and algorithmic analysis. CTCs, defined as traditional (CK+ CD45- w/ intact DAPI nuclei and morphologically distinct) or CK- (CK-, CD45-, intact and distinct) were identified. PD-L1 biomarker characterization was assessed by IF staining, and UroVysion FISH testing was used to assess genomic abnormalities in a subset of patient samples. Additionally, WBCs (CD45+ cells) were assessed for PD-L1 expression. Results: Traditional CTCs were detected in 6/12 (50%) patients. 3/12 (25%) patients had PD-L1+ cells, 2 of these patients were exclusively CK-/PD-L1+ CTCs, which were confirmed as cancer via FISH. CK- CTCs were detected in 83% (10/12) patients. 5 patients had greater than 4 fold PD-L1 positivity in WBCs as compared to healthy donor controls. Conclusions: MIBC and mBCa patients have detectable CTCs with a high frequency of CK-/PD-L1+ CTCs. Utilization of a liquid biopsy to identify patients with PD-L1+ CTCs and PD-L1+ WBCs may enable both patient selection or short term therapeutic monitoring for measuring pharmacodynamics to ensure therapy effectiveness. Further studies are planned to investigate association of PD-L1+ CTCs and WBCs with response to PD-1 and PD-L1 checkpoint immunotherapy.


2013 ◽  
Vol 28 (4) ◽  
pp. 348-356 ◽  
Author(s):  
Wings TY Loo ◽  
Michael CW Yip ◽  
Louis WC Chow ◽  
Qing Liu ◽  
Elizabeth LY Ng ◽  
...  

Background Short-term memory (STM) decline in breast cancer patients resulting from chemotherapy was evaluated by means of blood biomarkers, a questionnaire, and a computerized STM test. Methods This study was conducted from January 2013 to June 2013, recruiting 90 subjects: 30 breast cancer patients beginning the 3rd of 4th cycles of docetaxel and cyclophosphamide chemotherapy, 30 recovered patients (who completed 4 cycles of docetaxel for a minimum of 6 months), and 30 healthy subjects (disease-free females). The levels of hemoglobin, red and white blood cells, and cortisol in serum, and a computerized STM test were analyzed to estimate the effects of chemotherapy on STM. A questionnaire was given to all subjects to assess quality of life. Results Statistically significant differences were observed for the blood parameters (hemoglobin, red and white blood cells, and cortisol levels) between healthy and on-treatment subjects (respectively 13.47±0.96 g/dL vs 5.37±0.38 g/dL, 4.58±0.41 1012/L vs 2.07±0.13 1012/L, and 6.15±1.03 109/L vs 0.86±0.41 109/L). Scores of the STM test were significantly lower for patients compared to healthy subjects. As indicated by the results of the questionnaire, breast cancer patients had a higher tendency to forget than healthy controls (X2=3.15; p<0.0001) and recovered subjects (X2=3.15; p<0.0001). Conclusion We found depleted levels of hemoglobin, red and white blood cells as a result of chemotherapy, and elevated levels of stress correlated with poor performances in the computerized STM test. A higher cortisol level might be an important precursor of STM deterioration. Monitoring cortisol would be beneficial for evaluating the quality of life of breast cancer patients on chemotherapy.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Kumar Narayanan ◽  
Audrey Uy-Evanado ◽  
Carmen Teodorescu ◽  
Kyndaron Reinier ◽  
Karen Gunson ◽  
...  

Introduction: Although diabetes and renal dysfunction are known to be associated with SCD risk, the cumulative risk of objective laboratory markers in combination with left ventricular ejection fraction (LVEF) has not been previously evaluated. Hypothesis: Addition of glycosylated hemoglobin (HbA1C) and serum creatinine levels to LVEF can improve the SCD risk stratification model. Methods: As part of a large, prospective, ongoing study of SCD in a Northwestern US metropolitan region (catchment population about 1 million), SCD cases were compared with controls with coronary artery disease (CAD) and no SCD from the same geographic location. HbA1C, serum creatinine levels and LVEF (all prior and unrelated to the SCD event for cases) were obtained for all subjects. Odds ratios for SCD associated with abnormal HbA1C (≥ 7%) and creatinine (≥ 1.5 mg/dL) levels was calculated. Cumulative odds and improvement in model performance on addition of elevated lab markers to low LVEF (≤ 35%) was assessed. Results: 243 SCD cases (68.7 ± 13.2 yrs; 62.1% male) and 159 CAD controls (66.2 ± 9.9 yrs; 65.6% male) with appropriate lab values and LVEF information were evaluated. The mean HbA1C (7.3 ± 2.3 vs. 6.6 ± 1.5%) and creatinine (1.8 ± 1.7 vs. 1.2 ± 0.7 mg/dL) levels were significantly higher in cases. Cases were significantly more likely to have HbA1C ≥ 7% (49.4 vs. 27.7%; p<0.0001) or creatinine ≥ 1.5 mg/dL (39.1% vs. 13.8%) (all p<0.0001). After adjustment for age, sex and low LVEF, high HbA1C (OR 2.3, 95% CI 1.4-3.6; p=0.001) and high creatinine (OR 3.3, 95% CI 1.9-5.7; p<0.0001) were independently associated with SCD; LVEF ≤ 35% was associated as well (OR 1.8, 95% CI 1.1-3.2; p=0.05). As compared to neither lab marker being high, elevation of one marker (OR 2.4, 95% CI 1.5-3.9) or both markers (OR 7.9, 95% CI 3.5-17.6) was associated with progressive increase in SCD odds. Addition of lab markers to a risk stratification model with only LVEF improved model discrimination significantly (AUC 0.613 vs. 0.709; p=0.01). Conclusions: HbA1C and serum creatinine improved the SCD risk stratification model when added to LVEF. Further investigation is warranted before clinical use, including consideration of competing risks that influence overall mortality.


2021 ◽  
Author(s):  
Guanghou Fu ◽  
Kok Suen Cheng ◽  
Anqi Chen ◽  
Zhijie Xu ◽  
Xiaoyi Chen ◽  
...  

Abstract Background: Bladder cancer is characterized by its frequent recurrence and progression. Effective treatment strategies need to be based on an accurate risk stratification, in which muscle invasiveness and tumor grade represent the two most important factors. Traditional imaging techniques provide preliminary information about muscle invasiveness but are lacking in terms of accuracy. Although as the gold standard, pathological biopsy is only available after the surgery and cannot be performed longitudinally for long-term surveillance. Methods: In this work, we developed a microfluidic approach that interrogates circulating tumor cells (CTCs) in the peripheral blood of bladder cancer patients to reflect the risk stratification of the disease. Results:In a cohort of 48 bladder cancer patients comprising 33 non-muscle invasive bladder cancer (NMIBC) cases and 15 muscle invasive bladder cancer (MIBC) cases, the CTC count was found to be considerably higher in the MIBC group compared with the NMIBC group (4.67 vs. 1.88 CTCs/3 mL, P=0.019), and was significantly higher in high-grade bladder cancer patients verses low-grade bladder cancer patients (3.69 vs. 1.18 CTCs/3mL, P=0.024). Conclusions: This microfluidic assay of CTCs is believed to be a promising complementary tool for the risk stratification of bladder cancer.Trial registration: This research was conducted under the approval of the Ethics Committee of the First Affiliated Hospital at Zhejiang University School of Medicine with the Registration No. 2015-218.


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