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Cancers Aug 2021Breast cancer (BC) is the most frequently diagnosed cancer in women worldwide with more than 2 million new cases in 2020. Its incidence and death rates have increased... (Review)
Review
Breast cancer (BC) is the most frequently diagnosed cancer in women worldwide with more than 2 million new cases in 2020. Its incidence and death rates have increased over the last three decades due to the change in risk factor profiles, better cancer registration, and cancer detection. The number of risk factors of BC is significant and includes both the modifiable factors and non-modifiable factors. Currently, about 80% of patients with BC are individuals aged >50. Survival depends on both stage and molecular subtype. Invasive BCs comprise wide spectrum tumors that show a variation concerning their clinical presentation, behavior, and morphology. Based on mRNA gene expression levels, BC can be divided into molecular subtypes (Luminal A, Luminal B, HER2-enriched, and basal-like). The molecular subtypes provide insights into new treatment strategies and patient stratifications that impact the management of BC patients. The eighth edition of TNM classification outlines a new staging system for BC that, in addition to anatomical features, acknowledges biological factors. Treatment of breast cancer is complex and involves a combination of different modalities including surgery, radiotherapy, chemotherapy, hormonal therapy, or biological therapies delivered in diverse sequences.
PubMed: 34503097
DOI: 10.3390/cancers13174287 -
Cancer Communications (London, England) Jul 2020Low-grade endometrial stromal sarcoma (LG-ESS) is a rare tumor that lacks a prognostic prediction model. Our study aimed to develop a nomogram to predict overall...
BACKGROUND
Low-grade endometrial stromal sarcoma (LG-ESS) is a rare tumor that lacks a prognostic prediction model. Our study aimed to develop a nomogram to predict overall survival of LG-ESS patients.
METHODS
A total of 1172 patients confirmed to have LG-ESS between 1988 and 2015 were selected from the Surveillance, Epidemiology and End Results (SEER) database. They were further divided into a training cohort and a validation cohort. The Akaike information criterion was used to select variables for the nomogram. The discrimination and calibration of the nomogram were evaluated using concordance index (C-index), area under time-dependent receiver operating characteristic curve (time-dependent AUC), and calibration plots. The net benefits of the nomogram at different threshold probabilities were quantified and compared with those of the International Federation of Gynecology and Obstetrics (FIGO) criteria-based tumor staging using decision curve analysis (DCA). Net reclassification index (NRI) and integrated discrimination improvement (IDI) were also used to compare the nomogram's clinical utility with that of the FIGO criteria-based tumor staging. The risk stratifications of the nomogram and the FIGO criteria-based tumor staging were compared.
RESULTS
Seven variables were selected to establish the nomogram for LG-ESS. The C-index (0.814 for the training cohort and 0.837 for the validation cohort) and the time-dependent AUC (> 0.7) indicated satisfactory discriminative ability of the nomogram. The calibration plots showed favorable consistency between the prediction of the nomogram and actual observations in both the training and validation cohorts. The NRI values (training cohort: 0.271 for 5-year and 0.433 for 10-year OS prediction; validation cohort: 0.310 for 5-year and 0.383 for 10-year OS prediction) and IDI (training cohort: 0.146 for 5-year and 0.185 for 10-year OS prediction; validation cohort: 0.177 for 5-year and 0.191 for 10-year OS prediction) indicated that the established nomogram performed significantly better than the FIGO criteria-based tumor staging alone (P < 0.05). Furthermore, DCA showed that the nomogram was clinically useful and had better discriminative ability to recognize patients at high risk than the FIGO criteria-based tumor staging.
CONCLUSIONS
A prognostic nomogram was developed and validated to assist clinicians in evaluating prognosis of LG-ESS patients.
Topics: Endometrial Neoplasms; Female; Humans; Nomograms; SEER Program; Sarcoma, Endometrial Stromal; Survival Rate
PubMed: 32558385
DOI: 10.1002/cac2.12067 -
Nature Cancer Jan 2023Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor prognosis and limited treatment options. Here we provide a comprehensive census of the bone marrow...
Acute myeloid leukemia (AML) is a hematopoietic malignancy with poor prognosis and limited treatment options. Here we provide a comprehensive census of the bone marrow immune microenvironment in adult and pediatric patients with AML. We characterize unique inflammation signatures in a subset of AML patients, associated with inferior outcomes. We identify atypical B cells, a dysfunctional B-cell subtype enriched in patients with high-inflammation AML, as well as an increase in CD8GZMK and regulatory T cells, accompanied by a reduction in T-cell clonal expansion. We derive an inflammation-associated gene score (iScore) that associates with poor survival outcomes in patients with AML. Addition of the iScore refines current risk stratifications for patients with AML and may enable identification of patients in need of more aggressive treatment. This work provides a framework for classifying patients with AML based on their immune microenvironment and a rationale for consideration of the inflammatory state in clinical settings.
Topics: Adult; Humans; Child; Leukemia, Myeloid, Acute; Bone Marrow; T-Lymphocytes, Regulatory; Inflammation; Risk Assessment; Tumor Microenvironment
PubMed: 36581735
DOI: 10.1038/s43018-022-00480-0 -
Medicina (Kaunas, Lithuania) Aug 2022Pulmonary embolism (PE) can have a wide range of hemodynamic effects, from asymptomatic to a life-threatening medical emergency. Pulmonary embolism (PE) is associated... (Review)
Review
Pulmonary embolism (PE) can have a wide range of hemodynamic effects, from asymptomatic to a life-threatening medical emergency. Pulmonary embolism (PE) is associated with high mortality and requires careful risk stratification for individualized management. PE is divided into three risk categories: low risk, intermediate-risk, and high risk. In terms of initial therapeutic choice and long-term management, intermediate-risk (or submassive) PE remains the most challenging subtype. The definitions, classifications, risk stratification, and management options of intermediate-risk PE are discussed in this review.
Topics: Humans; Pulmonary Embolism; Risk Assessment
PubMed: 36143863
DOI: 10.3390/medicina58091186 -
Journal of Translational Medicine Mar 2023The incidence and mortality of gastric cancer ranks fifth and fourth worldwide among all malignancies, respectively. Accumulating evidences have revealed the close...
BACKGROUND
The incidence and mortality of gastric cancer ranks fifth and fourth worldwide among all malignancies, respectively. Accumulating evidences have revealed the close relationship between mitochondrial dysfunction and the initiation and progression of stomach cancer. However, rare prognostic models for mitochondrial-related gene risk have been built up in stomach cancer.
METHODS
In current study, the expression and prognostic value of mitochondrial-related genes in stomach adenocarcinoma (STAD) patients were systematically analyzed to establish a mitochondrial-related risk model based on available TCGA and GEO databases. The tumor microenvironment (TME), immune cell infiltration, tumor mutation burden, and drug sensitivity of gastric adenocarcinoma patients were also investigated using R language, GraphPad Prism 8 and online databases.
RESULTS
We established a mitochondrial-related risk prognostic model including NOX4, ALDH3A2, FKBP10 and MAOA and validated its predictive power. This risk model indicated that the immune cell infiltration in high-risk group was significantly different from that in the low-risk group. Besides, the risk score was closely related to TME signature genes and immune checkpoint molecules, suggesting that the immunosuppressive tumor microenvironment might lead to poor prognosis in high-risk groups. Moreover, TIDE analysis demonstrated that combined analysis of risk score and immune score, or stromal score, or microsatellite status could more effectively predict the benefit of immunotherapy in STAD patients with different stratifications. Finally, rapamycin, PD-0325901 and dasatinib were found to be more effective for patients in the high-risk group, whereas AZD7762, CEP-701 and methotrexate were predicted to be more effective for patients in the low-risk group.
CONCLUSIONS
Our results suggest that the mitochondrial-related risk model could be a reliable prognostic biomarker for personalized treatment of STAD patients.
Topics: Humans; Stomach Neoplasms; Tumor Microenvironment; Mitochondria; Adenocarcinoma; Prognosis
PubMed: 36915111
DOI: 10.1186/s12967-023-04033-6 -
Blood Cancer Journal May 2022Multiple myeloma (MM) is an acquired malignant plasma cell disorder that develops late in life. Although progression free and overall survival has improved across all... (Review)
Review
Multiple myeloma (MM) is an acquired malignant plasma cell disorder that develops late in life. Although progression free and overall survival has improved across all age, race, and ethnic groups, a subset of patients have suboptimal outcomes and are labeled as having high risk disease. A uniform approach to risk in NDMM remains elusive despite several validated risk stratification systems in clinical use. While we attempt to capture risk at diagnosis, the reality is that many important prognostic characteristics remain ill-defined as some patients relapse early who were defined as low risk based on their genomic profile at diagnosis. It is critical to establish a definition of high risk disease in order to move towards risk-adapted treatment approaches. Defining risk at diagnosis is important to both effectively design future clinical trials and guide which clinical data is needed in routine practice. The goal of this review paper is to summarize and compare the various established risk stratification systems, go beyond the R-ISS and international myeloma working group risk stratifications to evaluate specific molecular and cytogenetic abnormalities and how they impact prognosis independently. In addition, we explore the wealth of new genomic information from recent whole genome/exome sequencing as well as gene expression data and review known clinical factors affecting outcome such as disease burden and early relapse as well as patient related factors such as race. Finally, we provide an outlook on developing a new high risk model system and how we might make sense of co-occurrences, oncogenic dependencies, and mutually exclusive mutations.
Topics: Humans; Multiple Myeloma; Neoplasm Recurrence, Local; Neoplasm Staging; Paraproteinemias; Prognosis
PubMed: 35637223
DOI: 10.1038/s41408-022-00679-5 -
Cancers Sep 2021Along with the evolution of immunophenotypic and molecular diagnostics, the assessment of Minimal Residual Disease (MRD) has progressively become a keystone in the... (Review)
Review
Along with the evolution of immunophenotypic and molecular diagnostics, the assessment of Minimal Residual Disease (MRD) has progressively become a keystone in the clinical management of hematologic malignancies, enabling valuable post-therapy risk stratifications and guiding risk-adapted therapeutic approaches. However, specific prognostic values of MRD in different hematological settings, as well as its appropriate clinical uses (basically, when to measure it and how to deal with different MRD levels), still need further investigations, aiming to improve standardization and harmonization of MRD monitoring protocols and MRD-driven therapeutic strategies. Currently, MRD measurement in hematological neoplasms with bone marrow involvement is based on advanced highly sensitive methods, able to detect either specific genetic abnormalities (by PCR-based techniques and next-generation sequencing) or tumor-associated immunophenotypic profiles (by multiparametric flow cytometry, MFC). In this review, we focus on the growing clinical role for MFC-MRD diagnostics in hematological malignancies-from acute myeloid and lymphoblastic leukemias (AML, B-ALL and T-ALL) to chronic lymphocytic leukemia (CLL) and multiple myeloma (MM)-providing a comparative overview on technical aspects, clinical implications, advantages and pitfalls of MFC-MRD monitoring in different clinical settings.
PubMed: 34572809
DOI: 10.3390/cancers13184582 -
Journal of Personalized Medicine Jul 2021Technological innovations including risk-stratification algorithms and large databases of longitudinal population health data and genetic data are allowing us to develop... (Review)
Review
Technological innovations including risk-stratification algorithms and large databases of longitudinal population health data and genetic data are allowing us to develop a deeper understanding how individual behaviors, characteristics, and genetics are related to health risk. The clinical implementation of risk-stratified screening programmes that utilise risk scores to allocate patients into tiers of health risk is foreseeable in the future. Legal and ethical challenges associated with risk-stratified cancer care must, however, be addressed. Obtaining access to the rich health data that are required to perform risk-stratification, ensuring equitable access to risk-stratified care, ensuring that algorithms that perform risk-scoring are representative of human genetic diversity, and determining the appropriate follow-up to be provided to stratification participants to alert them to changes in their risk score are among the principal ethical and legal challenges. Accounting for the great burden that regulatory requirements could impose on access to risk-scoring technologies is another critical consideration.
PubMed: 34442379
DOI: 10.3390/jpm11080736 -
Eye (London, England) Oct 2023Glaucoma is the leading cause of preventable sight loss in the United Kingdom and the provision of timely glaucoma care has been highlighted as a significant challenge... (Review)
Review
Glaucoma is the leading cause of preventable sight loss in the United Kingdom and the provision of timely glaucoma care has been highlighted as a significant challenge in recent years. Following a recent high-profile investigation, The Healthcare Safety Investigation Branch recommended the validation of risk stratification models to safeguard the vision-related quality of life of glaucoma patients. There continues to be no nationally agreed evidence-based risk stratification model for glaucoma care across the United Kingdom. Some models have used simple measures of disease staging such as visual field mean deviation as surrogates for risk, but more refined, individualised risk stratification models should include factors related to both visual impairment and visual disability. Candidate tools should also incorporate both ocular and systemic co-morbidities, rate of disease progression, visual needs and driving status and undergo clinical refinement and validation to justify implementation. The disruption to routine glaucoma care caused by the COVID-19 pandemic has only highlighted the importance of such risk stratification models and has accelerated their development, application and evaluation. This review aims to critically appraise the available evidence underpinning current approaches for glaucoma risk stratification and to discuss how these may be applied to contemporary glaucoma care within the United Kingdom. Further research will be essential to justify and validate the utility of glaucoma risk stratification models in everyday clinical practice.
Topics: Humans; Quality of Life; Pandemics; COVID-19; Glaucoma; Risk Assessment
PubMed: 36918628
DOI: 10.1038/s41433-023-02480-5 -
The International Journal of Angiology... Sep 2022Pulmonary embolism remains a leading cause of cardiovascular mortality. Presentation and outcomes are variable among patients and require rapid risk stratification for...
Pulmonary embolism remains a leading cause of cardiovascular mortality. Presentation and outcomes are variable among patients and require rapid risk stratification for assessment and prognosis, as well as selection of appropriate treatment. Over the past several decades, several different models and parameters have become available to assess risk and classify pulmonary embolism into different risk categories. Some patients may be candidates for early discharge or complete outpatient treatment, while some may require invasive diagnostics and intensive monitoring. In this review, we summarize contemporary guidelines and methods for classification and risk stratification in an effort to provide tools for physicians to use in their management of patients with acute pulmonary embolisms.
PubMed: 36157098
DOI: 10.1055/s-0042-1756218