Immune Signature-Based Risk Stratification and Prediction of Immunotherapy Efficacy for Bladder Urothelial Carcinoma

Immune-related genes (IRGs) are closely related to tumor progression and the immune microenvironment. Few studies have investigated the effect of tumor immune microenvironment on the survival and response to immune checkpoint inhibitors of patients with bladder urothelial carcinoma (BLCA). We constructed two IRG-related prognostic signatures based on gene–immune interaction for predicting risk stratification and immunotherapeutic responses. We also verified their predictive ability on internal and overall data sets. Patients with BLCA were divided into high- and low-risk groups. The high-risk group had poor survival, enriched innate immune-related cell subtypes, low tumor mutation burden, and poor response to anti-PD-L1 therapy. Our prognostic signatures can be used as reliable prognostic biomarkers, which may be helpful to screen the people who will benefit from immunotherapy and guide the clinical decision-making of patients with BLCA.

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Case Report: Pseudoprogression With Nivolumab and Bevacizumab Followed by Recurrent Immune-Related Pneumonitis in Urothelial Carcinoma With Lung Metastasis

Frontiers in Oncology ◽

10.3389/fonc.2020.611810 ◽

2021 ◽

Vol 10 ◽

Author(s):

Zizhong Yang ◽

Guoqing Zhang ◽

Qiong Sun ◽

Minglu Liu ◽

Jiakang Shao ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Clinical Decision Making ◽

Checkpoint Inhibitors ◽

Treatment Plan ◽

Immune Therapy ◽

Clinical Decision ◽

Antiangiogenic Agents ◽

Durable Response ◽

Special Events ◽

Anticancer Treatment

BackgroundCombination therapy with immune checkpoint inhibitors (ICIs) and antiangiogenic agents is generally effective and well tolerated and might be effective for metastatic urothelial carcinoma (UC). However, ICI treatment is often associated with unique responses, such as pseudoprogression and ICI-related pneumonitis (CIP), which may influence clinical decision making and affect treatment. Although there have been many studies on the mechanism of pseudoprogression and CIP, the characteristics and relationship of these special events in a clinical setting remain rarely reported.Case PresentationHere, we present a patient with lung metastatic UC who underwent surgery and two lines of chemotherapy. The programmed cell death-1 (PD-1) inhibitor nivolumab and antiangiogenics agent bevacizumab were used as maintenance treatments. The patient experienced pseudoprogression after 2 PD-1 inhibitor cycles. The lesions in both lungs were enlarged on computed tomography (CT) imaging, and treatments were continued for another two cycles, after which the tumor size decreased to below baseline, followed by a durable response. However, after 4 months of pseudoprogression, the patient then developed CIP. The CIP was responsive to glucocorticoid therapy but recurred during ICI rechallenge, leading to the termination of immune therapy. Ultimately, the patient achieved durable, stable disease for over 18 months without further anticancer treatment.ConclusionsOur case shows that pseudoprogression can occur in UC during immunotherapy even when combined with an effective antiangiogenic agent. In addition, pseudoprogression may be correlated with future adverse effects and a durable response. In the management of CIP, early rechallenge with ICIs may lead to CIP recurrence, which could be more severe and needs to be treated early and with appropriate drugs. Clinicians should be aware of atypical responses to ICIs and adjust the treatment plan accordingly.

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Endometrial Cancer Molecular Characterization: The Key to Identifying High-Risk Patients and Defining Guidelines for Clinical Decision-Making?

Cancers ◽

10.3390/cancers13163988 ◽

2021 ◽

Vol 13 (16) ◽

pp. 3988

Author(s):

Regina Esi Mensimah Baiden-Amissah ◽

Daniela Annibali ◽

Sandra Tuyaerts ◽

Frederic Amant

Keyword(s):

Decision Making ◽

High Risk ◽

Risk Stratification ◽

Clinical Decision Making ◽

Treatment Decision ◽

Risk Groups ◽

Clinical Decision ◽

The Cancer Genome Atlas ◽

Type I ◽

Molecular Features

Endometrial carcinomas (EC) are the sixth most common cancer in women worldwide and the most prevalent in the developed world. ECs have been historically sub-classified in two major groups, type I and type II, based primarily on histopathological characteristics. Notwithstanding the usefulness of such classification in the clinics, until now it failed to adequately stratify patients preoperatively into low- or high-risk groups. Pieces of evidence point to the fact that molecular features could also serve as a base for better patients’ risk stratification and treatment decision-making. The Cancer Genome Atlas (TCGA), back in 2013, redefined EC into four main molecular subgroups. Despite the high hopes that welcomed the possibility to incorporate molecular features into practice, currently they have not been systematically applied in the clinics. Here, we outline how the emerging molecular patterns can be used as prognostic factors together with tumor histopathology and grade, and how they can help to identify high-risk EC subpopulations for better risk stratification and treatment strategy improvement. Considering the importance of the use of preclinical models in translational research, we also discuss how the new patient-derived models can help in identifying novel potential targets and help in treatment decisions.

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Early Identification of Patients with Acute Gastrointestinal Bleeding using Electronic Health Record Phenotyping

10.1101/2020.07.06.20136374 ◽

2020 ◽

Author(s):

Dennis Shung ◽

Cynthia Tsay ◽

Loren Laine ◽

Prem Thomas ◽

Caitlin Partridge ◽

...

Keyword(s):

Risk Stratification ◽

Gastrointestinal Bleeding ◽

Real Time ◽

Decision Rule ◽

Language Processing ◽

Clinical Decision Making ◽

External Validation ◽

Clinical Decision ◽

Internal Validation ◽

Electronic Health

Background and AimGuidelines recommend risk stratification scores in patients presenting with gastrointestinal bleeding (GIB), but such scores are uncommonly employed in practice. Automation and deployment of risk stratification scores in real time within electronic health records (EHRs) would overcome a major impediment. This requires an automated mechanism to accurately identify (“phenotype”) patients with GIB at the time of presentation. The goal is to identify patients with acute GIB by developing and evaluating EHR-based phenotyping algorithms for emergency department (ED) patients.MethodsWe specified criteria using structured data elements to create rules for identifying patients, and also developed a natural-language-processing (NLP)-based algorithm for automated phenotyping of patients, tested them with tenfold cross-validation (n=7144) and external validation (n=2988), and compared them with the standard method for encoding patient conditions in the EHR, Systematized Nomenclature of Medicine (SNOMED). The gold standard for GIB diagnosis was independent dual manual review of medical records. The primary outcome was positive predictive value (PPV).ResultsA decision rule using GIB-specific terms from ED triage and from ED review-of-systems assessment performed better than SNOMED on internal validation (PPV=91% [90%-93%] vs. 74% [71%-76%], P<0.001) and external validation (PPV=85% [84%-87%] vs. 69% [67%-71%], P<0.001). The NLP algorithm (external validation PPV=80% [79-82%]) was not superior to the structured-datafields decision rule.ConclusionsAn automated decision rule employing GIB-specific triage and review-of-systems terms can be used to trigger EHR-based deployment of risk stratification models to guide clinical decision-making in real time for patients with acute GIB presenting to the ED.

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Flow cytometry, cellular DNA content, and prognosis in human malignancy.

Journal of Clinical Oncology ◽

10.1200/jco.1987.5.10.1690 ◽

1987 ◽

Vol 5 (10) ◽

pp. 1690-1703 ◽

Cited By ~ 192

Author(s):

D E Merkel ◽

L G Dressler ◽

W L McGuire

Keyword(s):

Flow Cytometry ◽

Data Base ◽

Dna Content ◽

Dna Analysis ◽

Clinical Decision Making ◽

Risk Groups ◽

Clinical Decision ◽

Tumor Type ◽

Cellular Dna ◽

Bladder Carcinomas

The use of flow cytometry to analyze the cellular DNA content of human malignancies has become increasingly commonplace. The relationship between abnormalities in DNA content or proliferative characteristics and prognosis is becoming clear for a variety of malignancies in part through new techniques that permit analysis of archival material. High- and low-risk groups of patients with early breast and bladder carcinomas, non-small-cell lung cancer, and colorectal, ovarian, and cervical carcinoma can be distinguished on the basis of abnormal stemline DNA content. In several hematologic and common pediatric malignancies, the prognostic relevance of DNA content flow cytometry has been similarly established. Though the interpretation of tumor cell cycle analyses is less certain, this characteristic may also be prognostically important. However, generalizations cannot be made when applying flow cytometric DNA analysis to clinical decision making. The prognostic importance of an abnormal DNA histogram for an individual patient must be assessed on the basis of the relevant data base for that particular tumor type. The current extent of this data base for various malignancies is reviewed.

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P1858Meta-analysis of performance of risks scores for predicting outcomes after percutaneous Mitraclip implantation

European Heart Journal ◽

10.1093/eurheartj/ehz748.0609 ◽

2019 ◽

Vol 40 (Supplement_1) ◽

Author(s):

T K M Wang ◽

M T M Wang

Keyword(s):

Confidence Interval ◽

Risk Stratification ◽

Clinical Decision Making ◽

Operative Mortality ◽

Data Extraction ◽

Meta Analysis ◽

Critical Role ◽

Clinical Decision ◽

Risk Scores ◽

Sts Score

Abstract Background The Mitraclip is the most established percutaneous mitral valve intervention indicated for severe mitral regurgitation at high or prohibitive surgical risk. Risk stratification plays a critical role in selecting the appropriate treatment modality in high risk valve disease patients but have been rarely studied in this setting. We compared the performance of risk scores at predicting mortality after Mitraclip in this meta-analysis. Methods MEDLINE, Embase and Cochrane databases from 1 January 1980 to 31 December 2018 were searched. Two authors reviewed studies which reported c-statistics of risk models to predict mortality after Mitraclip for inclusion, followed by data extraction and pooled analyses. Results Amongst 494 articles searched, 47 full-text articles were evaluated, and 4 studies totalling 879 Mitraclip cases were included for analyses. Operative mortality was reported at 3.3–7.4% in three studies, and 1-year mortality 11.2%-13.5% in two studies. C-statistics (95% confidence interval) for operative mortality were EuroSCORE 0.66 (0.57–0.75), EuroSCORE II 0.72 (0.60–0.85) and STS Score 0.64 (0.56–0.73). Respective Peto's odds ratios (95% confidence interval) to assess calibration were EuroSCORE 0.21 (0.14–0.31), EuroSCORE II 0.43 (0.24–0.76) and STS Score 0.36 (0.21–0.61). C-statistics (95% confidence interval) for 1-year mortality were EuroSCORE II 0.64 (0.57–0.70) and STS Score (0.58–0.64). Conclusion All scores over-estimated operative mortality, and EuroSCORE II had the best moderate discrimination while the other two scores were only modestly prognostic. Development of Mitraclip-specific scores may improve accuracy of risk stratification for this procedure to guide clinical decision-making.

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A “Lymphocyte MicroRNA Signature” as Predictive Biomarker of Immunotherapy Response and Plasma PD-1/PD-L1 Expression Levels in Patients with Metastatic Renal Cell Carcinoma: Pointing towards Epigenetic Reprogramming

Cancers ◽

10.3390/cancers12113396 ◽

2020 ◽

Vol 12 (11) ◽

pp. 3396

Author(s):

Lorena Incorvaia ◽

Daniele Fanale ◽

Giuseppe Badalamenti ◽

Chiara Brando ◽

Marco Bono ◽

...

Keyword(s):

Clinical Decision Making ◽

Checkpoint Inhibitors ◽

Predictive Biomarkers ◽

Predictive Biomarker ◽

Clinical Decision ◽

Mirna Expression Profile ◽

Immune Checkpoints ◽

Cancer Evolution ◽

Specific Subset ◽

Number Of Patients

Introduction of checkpoint inhibitors resulted in durable responses and improvements in overall survival in advanced RCC patients, but the treatment efficacy is widely variable, and a considerable number of patients are resistant to PD-1/PD-L1 inhibition. This variability of clinical response makes necessary the discovery of predictive biomarkers for patient selection. Previous findings showed that the epigenetic modifications, including an extensive microRNA-mediated regulation of tumor suppressor genes, are key features of RCC. Based on this biological background, we hypothesized that a miRNA expression profile directly identified in the peripheral lymphocytes of the patients before and after the nivolumab administration could represent a step toward a real-time monitoring of the dynamic changes during cancer evolution and treatment. Interestingly, we found a specific subset of miRNAs, called “lymphocyte miRNA signature”, specifically induced in long-responder patients (CR, PR, or SD to nivolumab >18 months). Focusing on the clinical translational potential of miRNAs in controlling the expression of immune checkpoints, we identified the association between the plasma levels of soluble PD-1/PD-L1 and expression of some lymphocyte miRNAs. These findings could help the development of novel dynamic predictive biomarkers urgently needed to predict the potential response to immunotherapy and to guide clinical decision-making in RCC patients.

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Orale Antikoagulation bei chronischer Beinischämie

VASA ◽

10.1024/0301-1526.30.2.83 ◽

2001 ◽

Vol 30 (2) ◽

pp. 83-88

Author(s):

U. Mueller-Kolck

Keyword(s):

Oral Anticoagulation ◽

Clinical Decision Making ◽

Risk Model ◽

Anticoagulation Therapy ◽

Limb Ischemia ◽

Risk Groups ◽

Clinical Decision ◽

Arterial Disease ◽

Bleeding Complications ◽

Minor Bleeding

This review article summarizes clinical data on adjuvant long-term oral anticoagulation therapy (OAC) of peripheral arterial disease (PAD). It analyzes the underlying risk model of oral anticoagulation. Definitions of runoff patterns, of major and minor bleeding complications, of predictors of major bleedings as well as a classification of patient risk groups are described. The indication for OAC treatment of chronic limb ischemia remains still due to an individual decision. Clinical decision making is facilitated by the risk model. Improved oral anticoagulation control results in fewer bleeding complications. Studies on patient weekly self-testing and self-dosing which support this hypothesis are reviewed in the context of adjuvant OAC therapy.

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The effect of antibiotic use on immune-checkpoint inhibitor efficacy in patients with advanced urothelial carcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e17116 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e17116-e17116

Author(s):

Mohammad Khan ◽

Nathan Radakovich ◽

Brian I. Rini ◽

Omar Y. Mian ◽

Moshe Chaim Ornstein ◽

...

Keyword(s):

Urothelial Carcinoma ◽

Immune Checkpoint ◽

Checkpoint Inhibitors ◽

Cleveland Clinic ◽

Poor Response ◽

Antibiotic Use ◽

Treated Group ◽

Beta Lactams ◽

Kaplan Meier ◽

Advanced Urothelial Carcinoma

e17116 Background: There is emerging evidence that antibiotic (Abx) use may be associated with poor response to immune-checkpoint inhibitors (ICIs) in patients (pts) with some solid tumors. However, this has not been studied in metastatic urothelial carcinoma (mUC). We examined the effect of Abx use on outcomes in pts receiving ICIs for mUC. Methods: We retrospectively reviewed adult pts receiving ICIs for mUC treated at Cleveland Clinic between 2015 and 2020. Pts included in the study received > / = 3 cycles of ICI therapy with either azetolizumab or pembrolizumab. Abx use was defined as at least 3 days of Abx in the 60 days preceding or following ICI initiation. PFS and OS were estimated using the Kaplan-Meier method and a Cox proportional hazard model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CI). Results: A total of 69 pts with mUC receiving ICI therapy were included. The Abx-treated group consisted of 22 pts (32%) and the Abx-untreated group was 47 pts (68 %). 30 pts had Abx 60 days prior to ICI initiation and 20 patients had Abx within 60 days of ICI initiation. Abx use 60 days prior to ICI was not associated with PFS (HR = 0.91, 95% CI = 0.42-1.95) or OS (HR = 0.52, 95% CI = 0.33-1.68). Abx use during the first 60 days of ICI use was associated with decreased PFS (HR = 2.23, 95% CI = 1.03-4.86) but not OS (HR = 2.01, 95% CI = 0.89-4.53). Notably, there was no effect on response rates. The most commonly used Abx prior to treatment were: fluoroquinolones (30%); cephalosporins (26%); non-cephalosporin beta lactams (17%); and trimethoprim-sulfamethoxasole (13%). The most commonly used Abx after treatment initiation were: fluoroquinolones (17% of patients); cephalosporins (13%); non-cephalosporin beta lactams (12%); and trimethoprim-sulfamethoxasole (9%). Our study was insufficiently powered to address the effect of different antibiotic classes on outcomes. Conclusions: In our study, Abx use within first 60 days of treatment with ICIs was associated with decreased PFS and a trend toward decreased OS in pts with mUC but not in pts receiving Abx 60 days prior to ICI therapy. While the numbers are small, this is the first report exploring the effect of Abx on ICI response in mUC and further studies in larger databases are warranted.

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