Effect of concurrent beta-blocker (BB) use in patients receiving immune checkpoint inhibitors for metastatic urothelial (mUC) and renal cell carcinomas (mRCC).

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 467-467 ◽  
Author(s):  
Vaibhav G. Patel ◽  
William K. Oh ◽  
Matt D. Galsky ◽  
Bobby Chi-Hung Liaw ◽  
Che-Kai Tsao

467 Background: Stress-induced adrenergic signaling suppresses the immune system. A pre-clinical mouse model has shown that pharmacologic beta-blockade can stimulate CD8+ T-cell activity, and as a result improve efficacy of checkpoint inhibitors (CPI) to inhibit growth in solid tumors. Herein, we investigate the effect of BB on outcomes of patients receiving immunotherapy in mUC and mRCC. Methods: Using the Mount Sinai Genitourinary (GU) Cancer Biorepository, an IRB approved database containing all consented GU cancer patients seen between 2010-2018, we identified patients with either UC or RCC that have received CTLA-4 and/or PD-1/PD-L1 blockade. Patients who received only 1 dose of CPI were excluded from this analysis. A descriptive analysis was performed to assess clinical characteristics and treatment response. Overall Survival (OS) was calculated with Kaplan-Meier curves and cox proportional hazard models. Results: We identified 34 evaluable patients with mUC and 14 with mRCC that received CPI (Table). The median age at initiation was 69 years (39–91 years) and 81.2% (39/48) received prior chemotherapy and/or molecular targeted therapies. The mean duration of therapy was longer in the BB group compared to non-BB group (10.6 vs. 4.0 mo). For patients with mUC, the overall response rate (ORR) was 62.5% vs. 12.5% in favor of the BB group. For the patients with mRCC, the ORR was 40.0% vs. 10.0% in favor of the BB group. There were more outstanding responders (>1 year) in the BB group when compared with the non-BB group (41.2% vs. 6.5%). Patients with BB use had significantly improved median OS (NR vs. 11.6 mo, p = 0.004) when compared to those who did not receive BB. Conclusions: In this single-center cohort, the concurrent use of BB receiving CPI therapy is associated with an improved ORR, duration of therapy, and OS. Although this is hypothesis generating, the addition of BB is a promising strategy to improve response of immunotherapy, and prospective validation of this approach will be needed. [Table: see text]

2021 ◽  
Vol 20 ◽  
pp. 153303382110049
Author(s):  
Tao Ran ◽  
ZhiJi Chen ◽  
LiWen Zhao ◽  
Wei Ran ◽  
JinYu Fan ◽  
...  

Background and Objective: Gastric cancer (GC) is a common tumor malignancy with high incidence and poor prognosis. Laminin is an indispensable component of basement membrane and extracellular matrix, which is responsible for bridging the internal and external environment of cells and transmitting signals. This study mainly explored the association of the LAMB1 expression with clinicopathological characteristics and prognosis in gastric cancer. Methods: The expression data and clinical information of gastric cancer patients were downloaded from The Cancer Genome Atlas (TCGA) and Asian Cancer Research Group (ACRG). And we analyzed the relationship between LAMB1 expression and clinical characteristics through R. CIBERSORTx was used to calculate the absolute score of immune cells in gastric tumor tissues. Then COX proportional hazard models and Kaplan-Meier curves were performed to evaluate the role of LAMB1 and its influence on prognosis in gastric cancer patients. Finally, GO and KEGG analysis were applied for LAMB1-related genes in gastric cancer, and PPI network was constructed in Cytoscape software. Results: In the TCGA cohort, patients with gastric cancer frequently generated LAMB1 gene copy number variation, but had little effect on mRNA expression. Both in the TCGA and ACRG cohorts, the mRNA expression of LAMB1 in gastric cancer tissues was higher than it in normal tissues. All patients were divided into high expression group and low expression group according to the median expression level of LAMB1. The elevated expression group obviously had more advanced cases and higher infiltration levels of M2 macrophages. COX proportional hazard models and Kaplan-Meier curves revealed that patients with enhanced expression of LAMB1 have a worse prognosis. GO/KEGG analysis showed that LAMB1-related genes were enriched in PI3K-Akt signaling pathway, focal adhesion, ECM-receptor interaction, etc. Conclusions: The high expression of LAMB1 in gastric cancer is related to the poor prognosis of patients, and it may be related to microenvironmental changes in tumors.


2020 ◽  
Author(s):  
Antonio Dono ◽  
Victor Lopez-Rivera ◽  
Ankush Chandra ◽  
Cole T Lewis ◽  
Rania Abdelkhaleq ◽  
...  

Abstract Background Pleomorphic xanthoastrocytomas (PXA) are circumscribed gliomas that typically have a favorable prognosis. Limited studies have revealed factors affecting survival outcomes in PXA. Here, we analyzed the largest PXA dataset in the literature and identify factors associated with outcomes. Methods Using the Surveillance, Epidemiology, and End Results (SEER) 18 Registries database, we identified histologically confirmed PXA patients between 1994 and 2016. Overall survival (OS) was analyzed using Kaplan-Meier survival and multivariable Cox proportional hazard models. Results In total, 470 patients were diagnosed with PXA (males = 53%; median age = 23 years [14-39 years]), the majority were Caucasian (n = 367; 78%). The estimated mean OS was 193 months [95% CI: 179-206]. Multivariate analysis revealed that greater age at diagnosis (≥39 years) (3.78 [2.16-6.59], P < .0001), larger tumor size (≥30 mm) (1.97 [1.05-3.71], P = .034), and postoperative radiotherapy (RT) (2.20 [1.31-3.69], P = .003) were independent predictors of poor OS. Pediatric PXA patients had improved survival outcomes compared to their adult counterparts, in which chemotherapy (CT) was associated with worse OS. Meanwhile, in adults, females and patients with temporal lobe tumors had an improved survival; conversely, tumor size ≥30 mm and postoperative RT were associated with poor OS. Conclusions In PXA, older age and larger tumor size at diagnosis are risk factors for poor OS, while pediatric patients have remarkably improved survival. Postoperative RT and CT appear to be ineffective treatment strategies while achieving GTR confer an improved survival in male patients and remains the cornerstone of treatment. These findings can help optimize PXA treatment while minimizing side effects. However, further studies of PXAs with molecular characterization are needed.


2021 ◽  
Vol 12 (1) ◽  
pp. 17-26
Author(s):  
Genevieve C. Tuite ◽  
James A. Quintessenza ◽  
Alfred Asante-Korang ◽  
Sharon R. Ghazarian ◽  
Bethany L. Wisotzkey ◽  
...  

Background: To assess changes in patterns of practice and outcomes over time, we reviewed all patients who underwent heart transplantation (HTx) at our institution and compared two consecutive eras with significantly different immunosuppressive protocols (cohort 1 [80 HTx, June 1995-June 2006]; cohort 2 [108 HTx, July 2006-September 2018]). Methods: Retrospective study of 180 patients undergoing 188 HTx (June 1995-September 2018; 176 first time HTx, 10 second HTx, and 2 third HTx). In 2006, we commenced pre-HTx desensitization for highly sensitized patients and started using tacrolimus as our primary postoperative immunosuppressive agent. The primary outcome was mortality. Survival was modeled by the Kaplan-Meier method. Univariable and multivariable Cox proportional hazard models were created to identify prognostic factors for survival. Results: Our 188 HTx included 18 neonates, 85 infants, 83 children, and 2 adults (>18 years). Median age was 260.0 days (range: 5 days-23.8 years). Median weight was 7.5 kg (range: 2.2-113 kg). Patients in cohort 1 were less likely to have been immunosensitized preoperatively (12.5% vs 28.7%, P = .017). Nevertheless, Kaplan-Meier analysis suggested superior survival in cohort 2 ( P = .0045). Patients in cohort 2 were more likely to be alive one year, five years, and ten years after HTx. Multivariable analysis identified the earlier era (hazard ratio [HR] [95% confidence interval] for recent era = 0.32 [0.14-0.73]), transplantation after prior Norwood operation (HR = 4.44 [1.46-13.46]), and number of prior cardiac operations (HR = 1.33 [1.03-1.71]) as risk factors for mortality. Conclusions: Our analysis of 23 years of pediatric and congenital HTx reveals superior survival in the most recent 12-year era, despite the higher proportion of patients with elevated panel reactive antibody in the most recent era. This improvement was temporally associated with changes in our immunosuppressive strategy.


2020 ◽  
Author(s):  
Daniel C McFarland ◽  
Rebecca M. Saracino ◽  
Andrew H. Miller ◽  
William Breitbart ◽  
Barry Rosenfeld ◽  
...  

Background: Lung cancer-related inflammation is associated with depression. Both elevated inflammation and depression are associated with worse survival. However, outcomes of patients with concomitant depression and elevated inflammation are not known. Materials & methods: Patients with metastatic lung cancer (n = 123) were evaluated for depression and inflammation. Kaplan–Meier plots and Cox proportional hazard models provided survival estimations. Results: Estimated survival was 515 days for the cohort and 323 days for patients with depression (hazard ratio: 1.12; 95% CI: 1.05–1.179), 356 days for patients with elevated inflammation (hazard ratio: 2.85, 95% CI: 1.856–4.388), and 307 days with both (χ2 = 12.546; p < 0.001]). Conclusion: Depression and inflammation are independently associated with inferior survival. Survival worsened by inflammation is mediated by depression-a treatable risk factor.


BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Mesnad Alyabsi ◽  
Fouad Sabatin ◽  
Majed Ramadan ◽  
Abdul Rahman Jazieh

Abstract Background Colorectal cancer (CRC) is the most diagnosed cancer among males and third among females in Saudi Arabia, with up to two-third diagnosed at advanced stage. The objective of our study was to estimate CRC survival and determine prognostic factors. Methods Ministry of National Guard- Health Affairs (MNG-HA) registry data was utilized to identify patients diagnosed with CRC between 2009 and 2017. Cases were followed until December 30th, 2017 to assess their one-, three-, and five-year CRC-specific survivals. Kaplan-Meier method and Cox proportional hazard models were used to assess survival from CRC. Results A total of 1012 CRC patients were diagnosed during 2009–2017. Nearly, one-fourth of the patients presented with rectal tumor, 42.89% with left colon and 33.41% of the cases were diagnosed at distant metastasis stage. The overall one-, three-, and five-year survival were 83, 65 and 52.0%, respectively. The five-year survival was 79.85% for localized stage, 63.25% for regional stage and 20.31% for distant metastasis. Multivariate analyses showed that age, diagnosis period, stage, nationality, basis of diagnosis, morphology and location of tumor were associated with survival. Conclusions Findings reveal poor survival compared to Surveillance, Epidemiology, and End Results (SEER) population. Diagnoses at late stage and no surgical and/or perioperative chemotherapy were associated with increased risk of death. Population-based screening in this population should be considered.


Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Jacob P Kelly ◽  
Brad G Hammill ◽  
Jacob A Doll ◽  
G. Michael Felker ◽  
Paul A Heidenreich ◽  
...  

Background: In February 2014, coverage for cardiac rehabilitation (CR) was expanded by Centers for Medicare & Medicaid to include patients with chronic symptomatic heart failure (HF) on optimal medical therapy with ejection fraction <35%. Thus, we sought to characterize the patient population newly eligible for CR based on the expanded criteria and their associated outcomes. Methods: We analyzed the Get With The Guidelines-HF registry linked to Medicare claims data from 2008-2012 to assess three groups of patients age 65 or older: previously eligible (due to prior MI, CABG, stable angina, heart valve surgery, or PCI in the previous 12 months), newly eligible, and ineligible for CR. Ineligible patients met neither criteria. Incidence rate was calculated with Kaplan-Meier estimates and Cox proportional hazard models were used to determine the association of events. Results: Among 51,665 HF patients discharged alive, 27.2% (n=14,053) were newly eligible and 14.5% were previously eligible for CR (n=7477). Newly eligible patients were more likely to be black, have atrial fibrillation and EF < 35%, while having fewer previous hospitalizations than patients previously eligible for CR. Newly eligible and ineligible patients had similar risk for 1-year mortality compared with those previously eligible (adjusted Hazard Ratio [HR] 0.95, 95% Confidence Interval [CI] 0.88-1.02, p-value=0.13 and [HR] 1.05, 95% [CI] 0.98-1.13, p-value=0.17, respectively). However, newly eligible and ineligible patients had lower risk for 1-year readmission compared with those previously eligible (adjusted [HR] 0.89, 95% [CI] 0.85-0.93, p-value<0.001 and [HR] 0.94, 95% [CI] 0.90- 0.98, p-value<0.001). Conclusions: The extension of coverage for cardiac rehabilitation has tripled the potentially eligible HF population. As these newly eligible patients are at high risk for adverse outcomes, cardiac rehabilitation should be considered.


Author(s):  
Seunghan Kim ◽  
Byungyoon Yun ◽  
Seunghyun Lee ◽  
Changyoung Kim ◽  
Juho Sim ◽  
...  

The role of hazardous occupational noise exposure on the development of prediabetes is not well researched. We aimed to elucidate exposure to hazardous occupational noise as an independent risk factor for high fasting blood glucose (FBG). Participants exposed/non-exposed to occupational noise were recruited from the Common Data Model cohorts of 2013/2014 from two centers and were followed-up for 3 years. Multivariate time-dependent Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) and were adjusted for various covariates. Pooled HRs were calculated. Among the 43,858 participants of this retrospective cohort study, 37.64% developed high FBG. The mean (standard deviation) age in the cohort was 40.91 (9.71) years. In the fully adjusted models, the HRs of high FBG in the two centers were 1.35 (95% CI: 1.24–1.48) and 1.22 (95% CI: 1.17–1.28), and the pooled HR was 1.28 (95% CI: 1.16–1.41). A Kaplan–Meier plot of high FBG incidence by occupational noise exposure showed significant results (p < 0.001). We found that occupational noise exposure is significantly associated with high FBG. Preventing exposure to hazardous noise in the work environment may help reduce the risk for prediabetes among workers.


2020 ◽  
Author(s):  
Xingchen Li ◽  
Qichen Chen ◽  
Xinyu Bi ◽  
Jianjun Zhao ◽  
Zhiyu Li ◽  
...  

Abstract Background Recent studies suggest red blood cell distribution width (RDW) was a prognostic factor in various types of cancer patients, although the results are controversial. The objective of this study was to investigate the significance of RDW in patients with Intrahepatic cholangiocarcinoma (ICC) after radical resection. Method: The relationship between the preoperative serum RDW value and clinic pathological characteristics was analyzed in 157 ICC patients between January 2012 and June 2018 who underwent curative resection. X-tile software was used to determine 40.2 fl, 12.6% as the optimal cut-off value for RDW-SD and RDW-CV respectively. 153 patients were classified into the low RDW-SD (≤ 40.2, n = 53) group and the high RDW-SD (> 40.2, n = 104) group, low RDW-CV (≤ 12.6, n = 94) group and the high RDW-CV (> 12.6, n = 63). Based on the RDW-SD combined with RDW-CV(SCC), classified into SCC = 0, 1 and 2 group. Kaplan-Meier survival analysis and Cox proportional hazard models were used to examine the effect of RDW on survival. Results Kaplan-Meier curve analysis showed that Patients with RDW-SD > 40.2 were significantly associated with better OS (P = 0.004, median OS: 68.0 months versus 17.0 months). Patients with RDW-CV > 12.6 were significantly associated with better OS (P = 0.030, median OS: not reach versus 22.0 months). Compared with a SCC = 0 or SCC = 1, SCC = 2 was significantly associated with better OS (P < 0.001, median OS: not reach versus 33.0 months versus 16, respectively). In the multivariate analysis, RDW-SD > 40.2 fl (HR = 0.446, 95% CI: 0.262–0.760, P = 0.003), RDW-CV > 12.6% (HR = 0.425, 95%CI: 0.230–0.783, P = 0.006), SCC = 2 (HR = 0.270, 95%CI: 0.133–0.549, P < 0.001) were associated with favorable OS. The multivariate analysis showed RDW-SD, RDW-CV and SCC level were not independent prognostic factors for PFS. Conclusions Preoperative low levels of RDW are associated with poor survival in ICC after curative resection. This provides a new way for predicting the prognosis of ICC patients and more targeted intervention measures.


2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 584-584
Author(s):  
Sidney VanAlstine ◽  
Camryn Froerer ◽  
Andrew W Hahn ◽  
Jeffrey Gilreath ◽  
Neeraj Agarwal ◽  
...  

584 Background: Diarrhea occurs in ~50% patients with mRCC receiving VEGFTKIs, and is a common cause of VEGFTKI Rx dose reductions/delays/interruptions. Stool bacteroides level directly correlates with diarrhea in these patients on Rx with VEGFTKI (Pal SK, Clinical Cancer Research 2015, PMID:26152743). Hypothesis was that mRCC patients on incidental antibiotics (ABX) which also target stool bacteroides will have less diarrhea, leading to improved Rx compliance, and improved outcomes on VEGFTKI. Methods: A retrospective study of mRCC patients with MSKCC intermediate or poor risk mRCC on 1st line VEGFRTKIs between 2005-2017. ABX usage was categorized by ABX bacteroides sensitivity at anytime during Rx with 1st line VEGFTKI along with the total number of days on ABX. 1st line VEGFRTKI progression free survival (PFS) was assessed by Kaplan-Meier and Cox proportional hazard models. Results: 145 patients with intermediate (n = 123, 85%) or poor risk (n = 22, 15%) mRCC on a VEGFTKI were identified. ABX were prescribed incidentally in 50 (34%) patients. 18 patients were prescribed ABX with bacteroides coverage of which 13 had ABX with high sensitivity for bacteroides. The median number of days supplied of all ABX was 7 (IQR 1-15 days). The median number of days supplied of ABX with bacteroides coverage was 6 (IQR 1.5-15.5 days). The median PFS in those prescribed ABX with bacteroides sensitivity was 18 months versus 8 months in those prescribed no ABX (p = 0.067), and 9 months in those prescribed ABX without bacteroides sensitivity. Duration of bacteroides ABX coverage resulted in a hazard ratio of 0.92 (95% CI 0.83-0.99, p = 0.043) for each additional day an ABX with bacteroides coverage was prescribed compared to those with no ABX. Conclusions: In these hypothesis generating data, incidental targeting of stool bacteroides with ABX correlated with improved PFS in mRCC patients on 1st line VEGFTKIs. Data need validation. Equal contribution: SAV, CDF, AWH


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Hanumantha R Jogu ◽  
Parag A Chevli ◽  
Geeth Sandeep Nadella ◽  
Tareq S Islam ◽  
Abhishek Dutta ◽  
...  

Introduction: Despite being frequent and associated with poor outcomes, no guidelines exist addressing the management of myocardial injury after noncardiac surgery (MINS). We hypothesized that Antiplatelets (ATP) agents reduce 30-days mortality in MINS patients. Methods: We used data from the Wake-Up T2MI registry, which is a single-center, retrospective cohort of hospitalized adults with elevated troponin (cTn) I (> 99 th percentile reference upper limit is >0.04 ng/dL) without acute myocardial infarction in a 2-year period. Patients with the cardiac procedures were excluded and cTn obtained during hospitalization. MINS is defined as abnormally elevated cTn levels during or within 30 days after surgery. Kaplan-Meier curve and multivariate-adjusted Cox-proportional hazard models were performed to assess all-cause mortality at 30-days, 90-days, and 1-year among patients with and without ATPs upon discharge. Results: A total of 457 patients were included in the final analysis. There was no difference in sex, race, BMI, and peak cTn, except age among patients stratified by ATP on discharge. Prevalence of mortality was significantly lower at 30-days (2.6% vs 7%, p = 0.028), it was not significant at 90-days (9.6% vs. 11.8%, p = 0.440) and at 1-year (21.4% vs. 24.6%, p=0.421) in patients who were discharged on ATPs compared to non-ATPs. Survival benefit was significant at 30-days (log-rank p = 0.022), non-significant at 90-days (log-rank p = 0.292) and at 1-year (log-rank p = 180) in ATPs group compared to non-ATPs. In a multivariate-adjusted (adjusted for age, sex, race, and peak cTn) model, patients who were discharged on ATPs had a HR of 0.31 (0.120 - 0.799; p = 0.015) at 30 days, HR of 0.64 (0.363 - 1.136; p = 0.128) at 90 days (Figure 1), and HR of 0.69 (0.472 - 1.025; p = 0.066) at 1 year. Conclusions: In conclusion, antiplatelet agents on discharge were associated with decreased 30-days mortality in MINS patients. Further studies are needed to validate our results.


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