scholarly journals Clinical Impact of Sarcopenia and Inflammatory/Nutritional Markers in Patients with Unresectable Metastatic Urothelial Carcinoma Treated with Pembrolizumab

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 310
Author(s):  
Takuto Shimizu ◽  
Makito Miyake ◽  
Shunta Hori ◽  
Kazuki Ichikawa ◽  
Chihiro Omori ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Multivariate Analyses ◽  
Independent Predictor ◽  
Psoas Muscle ◽  
Progression Free Survival ◽  
Muscle Area ◽  
Psoas Major Muscle ◽  
Metastatic Urothelial Carcinoma ◽  
Psoas Major ◽  
The Impact

Sarcopenia is a muscle loss syndrome known as a risk factor of various carcinomas. The impact of sarcopenia and sarcopenia-related inflammatory/nutritional markers in metastatic urothelial carcinoma (mUC) treated with pembrolizumab was unknown, so this retrospective study of 27 patients was performed. Psoas muscle mass index (PMI) was calculated by bilateral psoas major muscle area at the L3 with computed tomography. The cut-off PMI value for sarcopenia was defined as ≤6.36 cm2/m2 for men and ≤3.92 cm2/m2 for women. Neutrophil-to-lymphocyte ratio (NLR) ≥ 4.0 and sarcopenia correlated with significantly shorter progression-free survival (PFS) (hazard ratio (HR) 3.81, p = 0.020; and HR 2.99, p = 0.027, respectively). Multivariate analyses identified NLR ≥ 4.0 and sarcopenia as independent predictors for PFS (HR 2.89, p = 0.025; and HR 2.79, p = 0.030, respectively). Prognostic nutrition index < 45, NLR ≥ 4.0 and sarcopenia were correlated with significantly worse for overall survival (OS) (HR 3.44, p = 0.046; HR 4.26, p = 0.024; and HR 3.92, p = 0.012, respectively). Multivariate analyses identified sarcopenia as an independent predictor for OS (HR 4.00, p = 0.026). Furthermore, a decrease in PMI ≥ 5% in a month was an independent predictor of PFS and OS (HR 12.8, p = 0.008; and HR 6.21, p = 0.036, respectively). Evaluation of sarcopenia and inflammatory/nutritional markers may help in the management of mUC with pembrolizumab.

Impact of clinicopathological features on survival in patients treated with immune-based combinations for metastatic urothelial carcinoma: A meta-analysis of randomized clinical trials.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16534-e16534
Author(s):  
Veronica Mollica ◽  
Alessandro Rizzo ◽  
Matteo Santoni ◽  
Andrea Marchetti ◽  
Matteo Rosellini ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Liver Metastases ◽  
Urothelial Carcinoma ◽  
Meta Analysis ◽  
Clinicopathological Features ◽  
Cochrane Library ◽  
Risk Of Death ◽  
Metastatic Urothelial Carcinoma ◽  
Ecog Ps ◽  
The Impact

e16534 Background: Immune checkpoint inhibitors (ICIs) have recently revolutionized the treatment landscape of metastatic urothelial carcinoma (mUC). Nonetheless, little is known regarding the impact of clinicopathological features in this setting. We performed a meta-analysis aiming to evaluate the predictive value of ECOG-PS, age, gender, liver metastases, and histology in randomized controlled trials (RCTs) comparing ICI-based combinations versus chemotherapy in mUC patients. Methods: We retrieved all the relevant RCTs through PubMed/Med, Cochrane library, and EMBASE; additionally, proceedings of the main international oncological meetings were also searched for relevant abstracts. Eligible studies included RCTs comparing ICI-based combinations versus chemotherapy alone in mUC patients. The primary endpoint was overall survival (OS), measured as hazard ratio (HR) with corresponding 95% confidence interval (CI). All statistical analyses were performed using R studio software. Results: Overall, 1032 mUC patients were included in the analysis. Compared with chemotherapy, ICI-based combinations significantly decreased the risk of death in several clinicopathological subgroups, including no liver metastases (HR, 0.84; 95% CI, 0.74-0.95) and ECOG-PS 0 patients (HR, 0.84; 95% CI, 0.72-0.97). Similarly, ICI-based combinations were associated with prolonged OS in mUC patients who were < 65 years old (HR, 0.82; 95% CI, 0.72-0.95), as well as in male (HR, 0.90; 95% CI, 0.82-0.99) and female patients (HR, 0.81; 95% CI, 0.68-0.97). Conversely, a non-statistically significant benefit was observed for chemotherapy alone in mUC patients with liver metastases (HR, 1.06; 95% CI, 0.86-1.31). Conclusions: According to our results, the magnitude of benefit of ICI-based combinations over chemotherapy in mUC was consistent across a number of clinicopathological subgroups, while a proportion of patients could respond to chemotherapy alone.Despite several limitations affect our analysis, we believe these results could guide in everyday treatment decision-making, also assisting in the design and interpretation of future clinical trials on ICIs in mUC.

The Impact of Gender on Outcomes in Patients With Metastatic Urothelial Carcinoma

2013 ◽  
Vol 11 (3) ◽  
pp. 346-352 ◽  
Author(s):  
Lindsay Haines ◽  
Aristotle Bamias ◽  
Susan Krege ◽  
Chia-Chi Lin ◽  
Noah Hahn ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Metastatic Urothelial Carcinoma ◽  
The Impact

scholarly journals Phase II California Cancer Consortium Trial of Gemcitabine-Eribulin Combination in Cisplatin-Ineligible Patients With Metastatic Urothelial Carcinoma: Final Report (NCI-9653)

2019 ◽  
Vol 37 (29) ◽  
pp. 2682-2688 ◽  
Author(s):  
Sarmad Sadeghi ◽  
Susan G. Groshen ◽  
Denice D. Tsao-Wei ◽  
Rahul Parikh ◽  
Amir Mortazavi ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Phase Ii ◽  
Performance Status ◽  
Objective Response ◽  
Evaluation Criteria ◽  
Progression Free Survival ◽  
Median Number ◽  
Final Report ◽  
Curative Surgery ◽  
Metastatic Urothelial Carcinoma

PURPOSE Patients with metastatic urothelial carcinoma are often ineligible for cisplatin-based treatments. A National Cancer Institute Cancer Therapy Evaluation Program–sponsored trial assessed the tolerability and efficacy of a gemcitabine-eribulin combination in this population. METHODS Patients with treatment-naïve advanced or recurrent metastatic urothelial carcinoma of the bladder, ureter, or urethra not amenable to curative surgery and not candidates for cisplatin-based therapy were eligible. Cisplatin ineligibility was defined as creatinine clearance less than 60 mL/min (but ≥ 30 mL/min), grade 2 neuropathy, or grade 2 hearing loss. Treatment was gemcitabine 1,000 mg/m2 intravenously followed by eribulin 1.4 mg/m2, both on days 1 and 8, repeated in 21-day cycles until progression or unacceptable toxicity. A Simon two-stage phase II trial design was used to distinguish between Response Evaluation Criteria in Solid Tumors, version 1.1 objective response rates of 20% versus 50%. RESULTS Between June 2015 and March 2017, 24 eligible patients with a median age of 73 years (range, 62 to 88 years) underwent therapy. Performance status of 0, 1, or 2 was seen in 11, 11, and two patients, respectively. Sites of disease included: lymph nodes, 16; lungs, nine; liver, seven; bladder, five; bones, two. Median number of cycles received was four (range, one to 16). Of 24 patients, 12 were confirmed responders; the observed objective response rate was 50% (95% CI, 29% to 71%). Median overall survival was 11.9 months (95% CI, 5.6 to 20.4 months), and median progression-free survival was 5.3 months (95% CI, 4.5 to 6.7 months). The most common treatment-related any-grade toxicities were fatigue (83% of patients), neutropenia (79%), anemia (63%), alopecia (50%), elevated AST (50%), and constipation, nausea, and thrombocytopenia (42% each). CONCLUSION Gemcitabine-eribulin treatment response and survival for cisplatin-ineligible patients compare favorably to other regimens. Additional research is needed.

A randomized comparison of cisplatin alone or in combination with methotrexate, vinblastine, and doxorubicin in patients with metastatic urothelial carcinoma: a cooperative group study.

1992 ◽  
Vol 10 (7) ◽  
pp. 1066-1073 ◽  
Author(s):  
P J Loehrer ◽  
L H Einhorn ◽  
P J Elson ◽  
E D Crawford ◽  
P Kuebler ◽  
...  
Keyword(s):  
Overall Survival ◽  
Urothelial Carcinoma ◽  
Response Rate ◽  
Combined Therapy ◽  
Single Agent ◽  
Progression Free Survival ◽  
Free Survival ◽  
Metastatic Urothelial Carcinoma ◽  
Advanced Urothelial Carcinoma ◽  
To Receive

PURPOSE A prospective randomized trial was performed to determine if the addition of methotrexate, vinblastine, and doxorubicin to cisplatin (M-VAC) imparted a response rate or a survival advantage over single-agent cisplatin in patients with advanced urothelial carcinoma. PATIENTS AND METHODS From October 1984 through May 1989, 269 patients with advanced urothelial carcinoma were entered onto this international intergroup trial and randomized to receive intravenous (IV) cisplatin (70 mg/m2) alone or with methotrexate (30 mg/m2 on days 1, 15, 22), vinblastine (3 mg/m2 on days 2, 15, 22) plus doxorubicin (30 mg/m2 on day 2). Cycles were repeated every 28 days until tumor progression or a maximum of six cycles. There were 246 fully assessable patients of whom 126 were randomized to cisplatin alone and 120 were randomized to the M-VAC regimen. RESULTS As expected, the M-VAC regimen was associated with a greater toxicity, especially leukopenia, mucositis, granulocytopenic fever, and drug-related mortality. Response rates were superior for the M-VAC regimen compared with single-agent cisplatin (39% v 12%; P less than .0001). Similarly, the progression-free survival (10.0 v 4.3 months) and overall survival (12.5 v 8.2 months) were significantly greater for the combined therapy arm. CONCLUSION Although a more toxic regimen, we found M-VAC to be superior to single-agent cisplatin with respect to response rate, duration of remission, and overall survival in patients with advanced urothelial carcinoma.

scholarly journals The impact of preoperative sarcopenia, defined based on psoas muscle area, on long-term outcomes of heart valve surgery

2019 ◽  
Vol 157 (3) ◽  
pp. 1071-1079.e3 ◽  
Author(s):  
Homare Okamura ◽  
Naoyuki Kimura ◽  
Keisuke Tanno ◽  
Makiko Mieno ◽  
Harunobu Matsumoto ◽  
...  
Keyword(s):  
Heart Valve ◽  
Psoas Muscle ◽  
Valve Surgery ◽  
Heart Valve Surgery ◽  
Long Term Outcomes ◽  
Muscle Area ◽  
The Impact

miR125 and miR200a as potential circulating miRNA biomarkers in metastatic urothelial carcinoma patients treated with docetaxel.

2015 ◽  
Vol 33 (7_suppl) ◽  
pp. 364-364
Author(s):  
Stephanie A. Mullane ◽  
Chensheng Willa Zhou ◽  
William Martin-Doyle ◽  
Massimo Loda ◽  
Toni K. Choueiri ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Urothelial Carcinoma ◽  
Progression Free Survival ◽  
Post Treatment ◽  
Poor Responders ◽  
Second Line ◽  
Circulating Mirnas ◽  
Circulating Mirna ◽  
Docetaxel Treatment ◽  
Metastatic Urothelial Carcinoma

364 Background: Docetaxel is frequently used as second-line therapy in advanced bladder cancer. The response rate is 10-15% with a median PFS of 2.5 months and without data showing improvement of QoL, however, some selected patients derive significant benefit. Understanding the mechanisms underlying the sensitivity of docetaxel in bladder cancer will help to customize treatment in second line. Circulating miRNAs have been shown to be predict outcome in GU malignancies (for example, prostate cancer). Using circulating miRNA can identify patients who will respond to therapy non-invasively. The main aim of our study was identify circulating miRNAs predicting docetaxel response in urothelial carcinoma (UC). Methods: We obtained pre- and post-treatment plasma samples from patients included in the zactima phase II clinical trial assigned to the placebo + docetaxel arm. RNA from plasma was extracted and RT-PCR was performed on both the pre- and post-treatment samples looking at miRNAs known to be important in docetaxel response1(miR125, miR27a, miR34a, miR429, miR141, miR200a, miR200c, miR 146a, and miR9). Samples were normalized by the mean global miRNA levels. We divided patients based on progression free survival (PFS) as good responders (>4 months PFS or 6 cycles) versus poor responders (<2 months PFS or progression at first evaluation). Differences in miRNA levels were assessed using the student t test (p<0.05). Results: miR125 and miR200a were shown to be significantly different between the poor and good responders (p=0.056 and p=0.028, respectfully) in the pre-docetaxel samples. Higher expression of both miRNAs correlated with a good response in our small patient cohort. Additional analysis comparing pre- and post-miRNA levels will be presented. Conclusions: miR125 and miR200a are potential extracellular biomarker to docetaxel treatment in metastatic UC.

Systemic immune-inflammation index to predict survival in patients with metastatic urothelial carcinoma treated with second-line vinflunine.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e17019-e17019
Author(s):  
Patrik Palacka ◽  
Jana Katolicka ◽  
Tana Albertova ◽  
Katarina Rejlekova ◽  
Jana Obertova ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Urothelial Carcinoma ◽  
Progression Free Survival ◽  
Second Line ◽  
Free Survival ◽  
Second Line Chemotherapy ◽  
Metastatic Urothelial Carcinoma ◽  
Immune Inflammation ◽  
Line Chemotherapy

e17019 Background: Based on our previous study, the systemic immune-inflammation index (SII) is a prognostic factor in patients with metastatic urothelial cancer (MUC) treated with platinum-based first-line chemotherapy. The objective of this retrospective analysis was to explore prognostic value of the SII at baseline of second-line chemotherapy with vinflunine in MUC population. Methods: We evaluated 70 consecutive MUC (53 bladder, 21 upper tract) patients (54 men) treated with second-line chemotherapy with vinflunine at four oncological departments since 2010. ECOG performance status (PS) ≤ 1 had 44 patients (pts.), haemoglobin < 10 g/dL was present in 25 pts. and liver involvement in 18 pts. SII was based on platelets (P), neutrophils (N) and lymphocytes (L) counts defined as PxN/L. This study population was dichotomized by median into low SII and high SII groups. Progression-free survival (PFS), overall survival (OS) and their 95% CI were estimated by Kaplan-Meier method and compared with logrank test. Results: At median follow-up of 9.0 months (1-29 months), 68 pts. experienced disease progression and 62 died. Pts. with low SII at baseline had significantly better PFS and OS opposite to those with high SII (HR = 0.61, 95% CI 0.37-1.00, p = 0.0318 for PFS, HR = 0.60, 95% CI 0.36-1.00, p = 0.0312 for OS, respectively). In addition to the prognostic factors by Bellmunt (ECOG PS ≥ 1, liver involvement, haemoglobin < 10 g/dL), we identified peritoneal metastases as a factor associated with significantly worse survival (HR = 0.28, 95% CI 0.11-0.72, p < 0.00001 for PFS, HR = 0.30, 95% CI 0.12-0.75, p < 0.00001 for OS, respectively). Conclusions: The SII at baseline of treatment with second-line vinflunine represents a prognostic factor for pts. with MUC. Based on SII, pts. could be stratified into clinical trials in future. MUC pts. with high SII might be candidates for a different treatment approach. Key Words: Metastatic Urothelial Carcinoma. Systemic Immune-Inflammation Index. Vinflunine. Progression-Free Survival. Overall Survival.

scholarly journals Predictive value of diabetes mellitus for freedom from arrhythmia recurrence after cryoballoon-guided pulmonary vein isolation

EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
D Guckel ◽  
K Isgandarova ◽  
L Bergau ◽  
M El Hamriti ◽  
G Imnadze ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Pulmonary Vein ◽  
Pulmonary Vein Isolation ◽  
Structural Changes ◽  
Multivariate Analyses ◽  
Independent Predictor ◽  
Female Gender ◽  
Relevant Implication ◽  
Severe Arrhythmia ◽  
The Impact

Abstract Funding Acknowledgements Type of funding sources: None. Background Diabetes mellitus (DM) has been identified to play an important role in the regulation of atrial fibrillation (AF). Data concerning the impact of DM on the development of individual arrhythmia substrates are still lacking. Purpose Therefore, the primary aim of this study was to examine the outcome of cryoballoon-guided pulmonary vein isolation (PVI) in patients (pts) suffering from DM and coexisting AF. Methods 523 consecutive pts undergoing initial PVI using the 2nd generation cryoballoon were analysed. 273 pts (52%) suffered from paroxysmal AF (PAF) (51 ± 23.2 years old, 26% female), 250 pts (48%) from persistent AF (PERS) (63.9 ± 10.0 years old, 30% female) and 69 pts (13%) were diagnosed with DM (68 ± 19.6 years old, 30% female). Follow-up (FU) visits were performed at 3, 6 and 12 months including 7-day Holter ECGs. Primary endpoint was the first documented recurrence of any atrial arrhythmia after a 3 months blanking period (&gt; 30 sec.). Results Within the observation period of 12 months AF recurrence occurred in 29% (n = 151 pts). Regardless of the coincidence of DM, PAF pts were significantly younger than those with PERS (p = 0.001). PAF pts additionally suffering from DM presented with a significantly higher risk for arrhythmia recurrence (p = 0.047). Multivariate analyses verified DM as a strong independent predictor for arrhythmia recurrence associated with a &gt; 4 fold higher risk for recurrence after ablation (p = 0.009, hazard ratio (HR) 4.363, confidence interval (CI) 1.46-13.07). PERS pts showed a slightly increased rate of arrhythmia recurrence when additional DM was diagnosed. In these patients multivariate analyses revealed that DM was associated with a 43% higher risk for arrhythmia recurrence (p = 0.321, HR 1.143, CI 0.59-2.22). Beyond that, severe gender disparities were observed with female gender as independent predictor for arrhythmia recurrence (p = 0.027*, HR 1.927, CI 1.079-3.440). Conclusions DM has relevant implication for arrhythmia recurrence after PVI. More distinct effects were observed in PAF patients following AF ablation. This could be related to more severe arrhythmia substrates in PAF pts suffering from DM compared to PAF pts without additional DM and even more substantial structural changes in PERS. Thus, individual paths in ablation management are required in these pts with AF and coexisting DM.

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