Emerging clinical phenotype of bone metastatic urothelial cancer (mUC): Association of early osseous metastases (EOM) and outcomes.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17007-e17007
Author(s):  
Ariel Ann Nelson ◽  
Robert Cronk ◽  
Aniko Szabo ◽  
Emily Lemke ◽  
Thomas A. Giever ◽  
...  
Keyword(s):  
Cox Regression ◽  
De Novo ◽  
Opioid Analgesic ◽  
Unmet Need ◽  
Chi Square ◽  
Cox Regression Analysis ◽  
Osseous Metastases ◽  
Kaplan Meier ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy

e17007 Background: Outcomes of patients (pts) with mUC with EOM have not thoroughly been described in the age of immuno-oncology. We hypothesized that EOM is associated with worse outcomes when compared to pts with non-osseous metastases (NOM). Methods: We used a multi-institutional database of pts with mUC who received systemic treatment (trt) between March 2005 and August 2019, to assess survival and palliative outcomes of pts with EOM vs NOM at the time of metastatic diagnosis (met dx). Wilcoxon rank-sum and chi-square tests were performed. Survival was estimated by Kaplan-Meier method, Cox regression analysis was performed. Results: We identified 270 pts, 72% men, mean age 67 ± 11 years, 28% never smokers. At met dx, 27% (n = 72) had ≥ 1 EOM; these pts were more likely to have de novo metastases vs. those with recurrent metastases (42% vs 19%, p < 0.001). Pts with EOM were more likely to have a change or stop in 1st line trt due to clinical progression (30.6% vs 15.7%, p = 0.006), and received fewer total lines of systemic trt, median of 1.0 (1.0-5.0) vs. 2.0 (1.0-8.0), p = 0.05. Pts with EOM had shorter median overall survival (OS) vs. those with NOM, (6.1 vs 13.7 months, p < .0001), HR = 2.79 (95% CI:1.95-3.97, p < .0001). Median OS was shorter for pts with EOM who received 1st line immune checkpoint inhibitor (n = 14) vs platinum-based chemotherapy (n = 43), (1.6 vs 9.1 months, p = 0.003). Pts with EOM received higher opioid analgesic doses at the first and last oncology outpatient visits compared to pts with NOM with mean morphine milligram equivalent (MME) dose of 60 ± 91 vs 28 ± 65 at first visit, p = 0.004, and 171 ± 214 vs. 94 ± 229 at last visit, p < 0.001. Conclusions: The presence of EOM in mUC is associated with worse outcomes vs. pts with NOM. Pts with EOM may benefit from 1st line platinum-based chemotherapy vs. checkpoint immunotherapy. Furthermore, pts with EOM experience more pain than pts with NOM and may benefit from early engagement with palliative care. Pts with EOM represent a population with a highly unmet need for systemic, targeted and/or radiation interventions. Molecular subtypes may further define these pts and analysis is planned. We encourage ongoing clinical trials to report outcomes in pts with EOM. A consensus on reporting of non-measurable disease is also needed. [Table: see text]

Early Bone Metastases are Associated with Worse Outcomes in Metastatic Urothelial Carcinoma

2021 ◽  
pp. 1-10
Author(s):  
Ariel A. Nelson ◽  
Robert J. Cronk ◽  
Emily A. Lemke ◽  
Aniko Szabo ◽  
Ali R. Khaki ◽  
...  
Keyword(s):  
Bone Metastases ◽  
Urothelial Carcinoma ◽  
Clinical Outcomes ◽  
De Novo ◽  
Opioid Analgesic ◽  
Multivariable Analysis ◽  
Unmet Need ◽  
Risk Of Death ◽  
Platinum Based Chemotherapy ◽  
Metastatic Urothelial Carcinoma

BACKGROUND: Outcomes of patients with metastatic urothelial carcinoma (mUC) with early bone metastases (eBM) vs no early bone metastases (nBM) have not thoroughly been described in the age of immuno-oncology. OBJECTIVE: To compare survival and other clinical outcomes in patients with eBM and nBM. METHODS: We used a multi-institutional database of patients with mUC treated with systemic therapy. Demographic, metastatic site, treatment patterns, and clinical outcomes were recorded. Wilcoxon rank-sum, chi-square tests were performed. Survival was estimated by Kaplan-Meier method; multivariable Cox analysis was performed. RESULTS: We identified 270 pts, 67%men, mean age 69±11 years. At metastatic diagnosis, 27%had≥1 eBM and were more likely to have de novo vs. recurrent metastases (42%vs 19%, p <  0.001). Patients with eBM had shorter overall survival (OS) vs. those with nBM, (6.1 vs 13.7 months, p <  0.0001). On multivariable analysis, eBM independently associated with higher risk of death, HR = 2.52 (95%CI: 1.75–3.63, p <  0.0001). OS was shorter for patients with eBM who received initial immune checkpoint inhibitor vs platinum-based chemotherapy, (1.6 vs 9.1 months, p = 0.02). Patients with eBM received higher opioid analgesic doses compared to patients with nBM and received quantitatively more palliative radiation. CONCLUSIONS: Patients with mUC and eBM have poorer outcomes, may benefit less from anti-PD-1/PD-L1 therapy and represent an unmet need for novel therapeutic interventions. Dedicated clinical trials, biomarker validation to assist in patient selection, as well as consensus on reporting of non-measurable disease are required.

CIP4 Expression is Associated With The Prognosis in Colorectal Cancer

2020 ◽  
Author(s):  
Keqian Zhang ◽  
Tianqi Mao ◽  
Zhicheng He ◽  
Xiaojiao Wu ◽  
Yu Peng ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Prognostic Significance ◽  
Lymphatic Invasion ◽  
Chi Square ◽  
Interacting Protein ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
Student’S T

Abstract Background: This study was conducted to detect the expression of Cdc42 interacting protein 4 (CIP4) in patients with colorectal cancer (CRC), and explore the role of CIP4 in prognosis of CRC patients.Methods: The expression of CIP4 mRNA was determined by quantitative real-time PCR (qRT-CPR) and compared by student’s t-test between groups. Relationships of clinical characteristics and CIP4 expression were analyzed by Chi-square test. Kaplan-Meier curves were used to estimate the overall survival of CRC patients. And Cox regression analysis was conducted to identify the prognostic biomarkers for CRC patients.Results: The qRT-PCR results showed that CRC tissues were detected with significantly high CIP4 mRNA expression compared with adjacent normal controls (P<0.0001). The overexpression of CIP4 in CRC tissues was influenced by distant metastasis (P=0.021), lymphatic invasion (P=0.012) and TNM stage (P=0.006). But, other clinical factors including age, gender, differentiation and tumor site were proved to have no obvious effects on CIP4 expression (all, P>0.05). The survival curves showed that patients with high CIP4 expression generally lived shorter than those with low CIP4 expression (P<0.001). In addition, the multivariate analysis revealed that differentiation (P=0.044, HR=1.631, 95%CI=1.013-2.626) and CIP4 expression (P=0.000, HR=5.283, 95%CI=3.138-8.893) were of great prognostic significance for CRC patients.Conclusion: Taken together, up-regulation of CIP4 in CRC tissues represented poor prognosis for patients.

Two-Year Outcomes of Orbital Atherectomy Combined With Drug-Coated Balloon Angioplasty for Treatment of Heavily Calcified Femoropopliteal Lesions

2020 ◽  
Vol 27 (3) ◽  
pp. 492-501 ◽  
Author(s):  
Damianos G. Kokkinidis ◽  
Omar Jawaid ◽  
David Cantu ◽  
Brad J. Martinsen ◽  
Zsuzsanna Igyarto ◽  
...  
Keyword(s):  
Cox Regression ◽  
De Novo ◽  
Combined Therapy ◽  
Statistical Significance ◽  
Retrospective Chart Review ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Effective Combination ◽  
Orbital Atherectomy ◽  
Procedural Complications

Purpose: To examine whether the combination of orbital atherectomy (OA) and drug-coated balloons (DCB) can lead to superior procedural and 2-year outcomes compared with DCB only in heavily calcified femoropopliteal (FP) lesions. Materials and Methods: A retrospective chart review was conducted to identify patients treated with DCB only or OA+DCB for de novo FP lesions at a single center over a 4-year period (2014–2017). In the observation period, 113 patients met the inclusion criteria: 63 treated with DCB only (mean age 69.0±8.6 years; 62 men) vs 50 treated with OA+DCB (mean age 70.3±7.1 years; 48 men). The OA+DCB group had higher calcification rates (78% with severe calcification vs 37% in the DCB only group). Propensity score matching (PSM) was used to adjust for baseline differences between the 2 groups. Cox regression analysis was used to compare the follow-up outcomes between lesions treated with OA+DCB vs DCB only. Results: No difference in procedural complications or success was found. After PSM adjustment, the OA+DCB group was associated with lower bailout stenting rates (39.4% vs 66.7% in the DCB only group; p=0.026). The 2 groups had similar long-term outcomes, although the OA+DCB arm had a trend toward reduced TLR rates that did not reach statistical significance. The Kaplan-Meier estimates for 2-year freedom from TLR were 76.1% for the OA+DCB group vs 55.5% for the DCB only group (p=0.109). Conclusion: OA+DCB is a safe and effective combination for the treatment of calcified FP lesions. The combined therapy decreased the bailout stenting rates in the adjusted analysis. Larger cohorts and randomized trials are needed to examine OA efficacy in FP lesions.

scholarly journals Incidence and Survival Trends of Bladder Rhabdomyosarcoma:A SEER-based Analysis of 125 Cases

2020 ◽  
Author(s):  
Pin Li ◽  
Huixia Zhou ◽  
Hualin Cao ◽  
Tao Guo ◽  
Weiwei Zhu ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Survival Time ◽  
Clinical Outcomes ◽  
Cox Regression ◽  
Survival Curve ◽  
Clinicopathological Characteristics ◽  
Chi Square ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Significant Factors

Abstract Background To elucidate the bladder rhabdomyosarcoma clinicopathological characteristics and reveal the prognostic factors. Methods We screened data from SEER database (1975-2016) stratified by age group, evaluated the differences between groups with Chi-square and Fisher’s test, conducted the Kaplan-Meier survival analysis and plotted the survival curve. The significant factors were brought into Cox regression analysis and calculated the HR(95%CI). Results About half of the patients who develop bladder RMS will be younger than 2 years of age. Embryonal RMS account for 76% of all histopathology types. Age at diagnosis more than 16-y (HR=6.595,95%CI:3.62-12.01, p=7.04e-10), NOT embryonal rhabdomyosarcoma (HR=3.61, 95%CI:1.99-6.549, p =4.1e-06), without radiotherapy combined or surgery alone (HR=4.382, 95%CI:1.99-6.549, p =2.4e-05) and not performed the surgery (HR=2.982,95%CI:1.263-7.039, p =0.0126) were negatively correlated with 5-year survival time, while race( p =0.341), whether performed the lymphadenectomy( p =0.722) showed no influence on survival time. Cox regression results show that age, histology, SEER stage, treatment combined or alone influence the clinical outcomes. Conclusions We demonstrated the demographic and characteristic of bladder rhabdomyosarcoma, identified and excluded the prognostic factors for the 5-year overall survival and clinical outcomes.

scholarly journals Effectiveness of durvalumab versus chemotherapy in metastatic urothelial cancer: an observational, indirect comparison

2020 ◽  
Vol 9 (3) ◽  
pp. 191-199
Author(s):  
Beth L Nordstrom ◽  
Mustafa Oguz ◽  
Bong Chul Chu ◽  
Mario Ouwens ◽  
Henrik-Tobias Arkenau ◽  
...  
Keyword(s):  
Overall Survival ◽  
Propensity Scores ◽  
Cox Regression ◽  
Indirect Comparison ◽  
Kaplan Meier ◽  
Metastatic Urothelial Cancer ◽  
Platinum Based Chemotherapy ◽  
Metastatic Urothelial Carcinoma ◽  
Chemotherapy Patients ◽  
Electronic Medical Record Database

Aim: To compare the overall survival of patients with metastatic urothelial carcinoma (mUC) who failed platinum-based chemotherapy and received durvalumab or chemotherapy. Patients & methods: In an indirect comparison of patients with mUC who failed platinum-based chemotherapy, those who received durvalumab in a single-arm study were matched to patients from the Flatiron oncology electronic medical record database who received chemotherapy (n = 158 for each cohort). Matching was based on propensity scores. Kaplan–Meier methods and Cox regression models were utilized. Results: Median overall survival was 11.2 months (95% CI: 7.2–16.9) for durvalumab versus 8.2 months (95% CI: 6.7–9.8) for chemotherapy (hazard ratio: 0.63; 95% CI: 0.48–0.84). Conclusion: As a second-line therapy for mUC, durvalumab was associated with longer overall survival than chemotherapy.

scholarly journals The relationship between RECK Gene Polymorphisms and the prognosis of cholangiocarcinoma

2020 ◽  
Author(s):  
Ning Wang ◽  
Yanni Li ◽  
Yanfang Zheng ◽  
Huoming Chen ◽  
Xiaolong Wen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Overall Survival Rate ◽  
Chi Square ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
The Relationship

Abstract Background The study was designed to examine the reversion inducing cysteine rich protein with Kazal motifs (RECK) levels in patients with cholangiocarcinoma (CCA) and assess its role in CCA prognosis. Methods Quantitative real-time PCR (qRT-PCR) was used to determine the expression of RECK mRNA in 127 pairs of CCA samples and controls. Chi-square test was conducted to analyze the effects of clinical features on RECK expression. Kaplan-Meier curves were plotted to determine the overall survival rate of CCA patients with different RECK expression. The prognostic biomarkers for CCA patients were identified using the Cox regression analysis. Results Significantly down-regulated expression of RECK mRNA was determined in CCA tissues compared to noncancerous controls (P < 0.05). Chi-square test suggested reduced RECK expression was related with invasion depth (P = 0.026), differentiation (P = 0.025), lymphatic metastasis (P = 0.010) and TNM stage (P = 0.015). However, age, sex, tumor size and family history had no significant links with RECK expression (all, P > 0.05). The survival curves showed that patients with low RECK expression had a shorter overall survival rate than those with high RECK expression. Both the univariate analysis (P = 0.000, HR = 5.290, 95%CI = 3.195–8.758) and multivariate analysis (P = 0.000, HR = 5.376, 95%CI = 2.231–8.946) demonstrated that RECK was an independent biomarker for predicting the outcomes of CCA patients. Conclusions Taken together, the expression of RECK was down-regulated in CCA and it might be an efficient biomarker for CCA patients.

scholarly journals The Complex Association Between Bariatric Surgery and Depression: a National Nested-Control Study

2021 ◽  
Author(s):  
Chanpreet Singh Arhi ◽  
Roise Dudley ◽  
Osama Moussa ◽  
Maddalena Ardissino ◽  
Samantha Scholtz ◽  
...  
Keyword(s):  
Bariatric Surgery ◽  
Cox Regression ◽  
De Novo ◽  
Practice Research ◽  
Clinical Practice Research Datalink ◽  
Cox Regression Analysis ◽  
Cox Proportional Hazard ◽  
Kaplan Meier ◽  
Reduce Weight Loss ◽  
History Of

Abstract Background Although bariatric surgery has been shown to reduce weight loss and obesity-related conditions, an improvement in depression remains unclear. The aim of this study was to determine whether bariatric surgery is associated with a resolution of depression, and the prevention of its onset. Method Patients with a BMI ≥ 30 kg/m2 who had undergone bariatric surgery were identified from the Clinical Practice Research Datalink (CPRD), matched 5:1 to controls. Cox regression analysis was used to determine the risk of developing de novo depression. Kaplan-Meier analysis compared the proportion of patients with no further consultations related to depression between the two groups. Results In total, 3534 patients who underwent surgery, of which 2018 (57%) had pre-existing depression, were matched to 15,480 controls. Cox proportional hazard modelling demonstrated surgery was associated with a HR of 1.50 (95% CI 1.32–1.71, p < 0.005) for developing de novo depression. For those with pre-existing depression, by 5 years, just over 20% of post-surgical patients had no further depression episodes compared with 17% of controls. Conclusion In individuals with a history of depression, bariatric surgery is associated with an improvement in mental health. On the contrary, the finding of increased de novo diagnoses of depression following surgery indicates the need for further study of the mechanisms by which bariatric surgery is associated with depression in this subset of patients.

scholarly journals Development of predictive prognostic nomogram for NECs of rectum on population-based exploration

2018 ◽  
Vol 7 (11) ◽  
pp. 1178-1185 ◽  
Author(s):  
Yang Lv ◽  
Ning Pu ◽  
Wei-lin Mao ◽  
Wen-qi Chen ◽  
Huan-yu Wang ◽  
...  
Keyword(s):  
Cox Regression ◽  
Population Based ◽  
Prognostic Indicators ◽  
Rank Test ◽  
Chi Square ◽  
Related Factors ◽  
Ki 67 ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Chi Square Test

Aim We aim to investigate the clinical characteristics of the rectal NECs and the prognosis-related factors and construct a nomogram for prognosis prediction. Methods The data of 41 patients and 1028 patients with rectal NEC were retrieved respectively from our institution and SEER database. OS or PFS was defined as the major study outcome. Variables were compared by chi-square test and t-test when appropriate. Kaplan–Meier analysis with log-rank test was used for survival analysis and the Cox regression analysis was applied. The nomogram integrating risk factors for predicting OS was constructed by R to achieve superior discriminatory ability. Predictive utility of the nomogram was determined by concordance index (C-index) and calibration curve. Results In the univariate and multivariate analyses, tumor differentiation, N stage, M stage and resection of primary site were identified as independent prognostic indicators. The linear regression relationship was found between the value of Ki-67 index and the duration of OS (P < 0.05). Furthermore, the independent prognostic factors were added to formulate prognostic nomogram. The constructed nomogram showed good performance according to the C-index. Conclusions Contrary to WHO classification guideline, we found that the rectal NEC diseases are heterogeneous and should be divided as different categories according to the pathological differentiation. Besides, the nomogram formulated in this study showed excellent discriminative capability to predict OS for those patients. More advanced predictive model for this disease is required to assist risk stratification via the formulated nomogram.

scholarly journals The expression of HOXA9 and its prognostic value in cervical cancer

2020 ◽  
Author(s):  
Keqian Zhang ◽  
Tianqi Mao ◽  
Zhicheng He ◽  
Xiaojiao Wu ◽  
Yu Peng ◽  
...  
Keyword(s):  
Cervical Cancer ◽  
Prognostic Value ◽  
Cox Regression ◽  
Figo Stage ◽  
Rank Test ◽  
Chi Square ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Chi Square Test

Abstract Background The HOXA9 gene, belonging to homeobox (HOX) gene family, has been recently reported dys-expressed in several kinds of human cancers. This study aimed to investigate the expression of HOXA9 and its prognostic value in cervical cancer. Methods The HOXA9 mRNA expression was detected with a quantitative real-time polymerase chain reaction (qRT-PCR) assay, and the association of HOXA9 expression with clinical characteristic was analyzed via chi-square test. Kaplan-Meier and cox regression analyses were conducted to estimate the prognostic value of HOXA9 in cervical cancer. Results HOXA9 expression was significantly down-expressed in cervical cancer tissues compared with that in adjacent normal tissues (P < 0.01). And the expression of HOXA9 was significantly associated with TNM stage, pathological grade, FIGO stage and differentiation (All P < 0.05). In addition, Kaplan–Meier analysis indicated that the overall survival of patients with low HOXA9 expression was shorter than those with high HOXA9 expression (log rank test, P = 0.000). Cox regression analysis revealed that HOXA9 had a high prognostic value in cervical cancer. Conclusion HOXA9 is down-regulated and involved in the development of cervical cancer. Moreover, it may be an useful independent prognostic bio-marker for patients with cervical cancer.

scholarly journals Rab25 Acts as a Promising Novel Bio-Marker in the Prognosis of Patients with Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Zhong Dai ◽  
Ke-Qing Yao ◽  
Xing-Sheng Hu ◽  
Yi-Qun Li ◽  
Yu-Tao Liu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Prognostic Value ◽  
Cox Regression ◽  
Rank Test ◽  
Chi Square ◽  
Cox Regression Analysis ◽  
Normal Tissues ◽  
Kaplan Meier ◽  
Chi Square Test ◽  
The Relationship

Abstract Background: Rab25 was indicated to be involved in several human tumors. However, the clinical significance of Rab25 in hepatocellular carcinoma (HCC) was still unclear. The purpose of this study was to investigate the expression and prognostic value of Rab25 in HCC.Methods: The relative mRNA expression levels of Rab25 in HCC tissues and adjacent normal tissues were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Chi-square test was used to analyze the relationship between Rab25 expression and clinical characteristics of patients. The prognostic value of Rab25 in HCC was estimated through Kaplan-Meier method and cox regression analysis.Results: Rab25 gene expression level was significantly higher in HCC tissues than that in normal tissues (P<0.001). Importantly, the increased Rab25 expression was closely associated with TNM stage (P=0.024), metastasis (P=0.022) and invasion classification (P=0.039). Moreover, patients with high Rab25 expression tended to have obviously shorter overall survival than those with low expression of Rab25 (log rank test, P<0.001) via Kaplan-Meier analysis. Univariate and multivariate cox regression analyses revealed that Rab25 was an independent prognostic factor of HCC.Conclusions: Rab25 is up-regulated in HCC and contributes to the progression of this tumor. What’s more, Rab25 may be a potential bio-marker for the prognosis of HCC.

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