-
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 -
PLoS Medicine Dec 2018A person's rate of aging has important implications for his/her risk of death and disease; thus, quantifying aging using observable characteristics has important...
BACKGROUND
A person's rate of aging has important implications for his/her risk of death and disease; thus, quantifying aging using observable characteristics has important applications for clinical, basic, and observational research. Based on routine clinical chemistry biomarkers, we previously developed a novel aging measure, Phenotypic Age, representing the expected age within the population that corresponds to a person's estimated mortality risk. The aim of this study was to assess its applicability for differentiating risk for a variety of health outcomes within diverse subpopulations that include healthy and unhealthy groups, distinct age groups, and persons with various race/ethnic, socioeconomic, and health behavior characteristics.
METHODS AND FINDINGS
Phenotypic Age was calculated based on a linear combination of chronological age and 9 multi-system clinical chemistry biomarkers in accordance with our previously established method. We also estimated Phenotypic Age Acceleration (PhenoAgeAccel), which represents Phenotypic Age after accounting for chronological age (i.e., whether a person appears older [positive value] or younger [negative value] than expected, physiologically). All analyses were conducted using NHANES IV (1999-2010, an independent sample from that originally used to develop the measure). Our analytic sample consisted of 11,432 adults aged 20-84 years and 185 oldest-old adults top-coded at age 85 years. We observed a total of 1,012 deaths, ascertained over 12.6 years of follow-up (based on National Death Index data through December 31, 2011). Proportional hazard models and receiver operating characteristic curves were used to evaluate all-cause and cause-specific mortality predictions. Overall, participants with more diseases had older Phenotypic Age. For instance, among young adults, those with 1 disease were 0.2 years older phenotypically than disease-free persons, and those with 2 or 3 diseases were about 0.6 years older phenotypically. After adjusting for chronological age and sex, Phenotypic Age was significantly associated with all-cause mortality and cause-specific mortality (with the exception of cerebrovascular disease mortality). Results for all-cause mortality were robust to stratifications by age, race/ethnicity, education, disease count, and health behaviors. Further, Phenotypic Age was associated with mortality among seemingly healthy participants-defined as those who reported being disease-free and who had normal BMI-as well as among oldest-old adults, even after adjustment for disease prevalence. The main limitation of this study was the lack of longitudinal data on Phenotypic Age and disease incidence.
CONCLUSIONS
In a nationally representative US adult population, Phenotypic Age was associated with mortality even after adjusting for chronological age. Overall, this association was robust across different stratifications, particularly by age, disease count, health behaviors, and cause of death. We also observed a strong association between Phenotypic Age and the disease count an individual had. These findings suggest that this new aging measure may serve as a useful tool to facilitate identification of at-risk individuals and evaluation of the efficacy of interventions, and may also facilitate investigation into potential biological mechanisms of aging. Nevertheless, further evaluation in other cohorts is needed.
Topics: Adult; Aged; Aged, 80 and over; Aging; Cohort Studies; Female; Follow-Up Studies; Humans; Male; Middle Aged; Morbidity; Mortality; Nutrition Surveys; Population Surveillance; Risk Factors; Young Adult
PubMed: 30596641
DOI: 10.1371/journal.pmed.1002718 -
World Journal of Gastroenterology Oct 2014Gastric cancer continues to be an important healthcare problem from a global perspective. Most of the cases in the Western world are diagnosed at late stages when the... (Review)
Review
Gastric cancer continues to be an important healthcare problem from a global perspective. Most of the cases in the Western world are diagnosed at late stages when the treatment is largely ineffective. Helicobacter pylori (H. pylori) infection is a well-established carcinogen for gastric cancer. While lifestyle factors are important, the efficacy of interventions in their modification, as in the use of antioxidant supplements, is unconvincing. No organized screening programs can be found outside Asia (Japan and South Korea). Although several screening approaches have been proposed, including indirect atrophy detection by measuring pepsinogen in the circulation, none of them have so far been implemented, and more study data is required to justify any implementation. Mass eradication of H. pylori in high-risk areas tends to be cost-effective, but its adverse effects and resistance remain a concern. Searches for new screening biomarkers, including microRNA and cancer-autoantibody panels, as well as detection of volatile organic compounds in the breath, are in progress. Endoscopy with a proper biopsy follow-up remains the standard for early detection of cancer and related premalignant lesions. At the same time, new advanced high-resolution endoscopic technologies are showing promising results with respect to diagnosing mucosal lesions visually and targeting each biopsy. New histological risk stratifications (classifications), including OLGA and OLGIM, have recently been developed. This review addresses the current means for gastric cancer primary and secondary prevention, the available and emerging methods for screening, and new developments in endoscopic detection of early lesions of the stomach.
Topics: Biopsy; Early Detection of Cancer; Gastroscopy; Humans; Life Style; Neoplasm Staging; Precancerous Conditions; Predictive Value of Tests; Preventive Health Services; Risk Assessment; Risk Factors; Risk Reduction Behavior; Stomach Neoplasms
PubMed: 25320521
DOI: 10.3748/wjg.v20.i38.13842 -
Cancer Metastasis Reviews Mar 2020Medulloblastoma (MB) is the most common malignant childhood tumor of the brain. Multimodal treatment consisting of surgery, radiation therapy, and chemotherapy reduced... (Review)
Review
Medulloblastoma (MB) is the most common malignant childhood tumor of the brain. Multimodal treatment consisting of surgery, radiation therapy, and chemotherapy reduced cumulative incidence of late mortality but increased the incidence of subsequent neoplasms and severe, incapacitating chronic health conditions. Present treatment strategies fail to recognize heterogeneity within patients despite wide divergence in individual responses. The persistent mortality rates and serious side effects of non-targeted cytotoxic therapies indicate a need for more refined therapeutic approaches. Advanced genomic research has led to the accumulation of an enormous amount of genetic information and resulted in a consensus distinguishing four molecular subgroups, WNT-activated, SHH-activated, and Group 3 and 4 medulloblastomas. These have distinct origin, demographics, molecular alterations, and clinical outcomes. Although subgroup affiliation does not predict response to therapy, new subgroup-specific markers of prognosis can enable a more layered risk stratification with additional subtypes within each primary subgroup. Here, we summarize subgroup-specific genetic alterations and their utility in current treatment strategies. The transition toward molecularly targeted interventions for newly diagnosed MBs remains slow, and prospective trials are needed to confirm stratifications based on molecular alterations. At the same time, numerous studies focus at fine-tuning the intensity of invasive radio- and chemotherapies to reduce intervention-related long-term morbidity. There are an increasing number of immunotherapy-based treatment strategies including immune checkpoint-inhibitors, oncolytic viruses, CAR-T therapy, and NK cells in recurrent and refractory MBs. Although most trials are in early phase, there is hope for therapeutic breakthroughs for advanced MBs within the next decade.
Topics: Biomarkers, Tumor; Cerebellar Neoplasms; Child; Clinical Trials as Topic; Humans; Medulloblastoma; Randomized Controlled Trials as Topic
PubMed: 31970590
DOI: 10.1007/s10555-020-09854-1 -
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 -
Haematologica Nov 2018The diagnosis of multiple myeloma can be challenging, even for experienced physicians, and requires close collaboration between numerous disciplines (orthopedics,... (Review)
Review
The diagnosis of multiple myeloma can be challenging, even for experienced physicians, and requires close collaboration between numerous disciplines (orthopedics, radiology, nuclear medicine, radiation therapy, hematology and oncology) before the final diagnosis of myeloma is made. The definition of multiple myeloma is based on the presence of clinical, biochemical, histopathological, and radiological markers of disease. Specific tests are needed both at presentation and during follow-up in order to reach the correct diagnosis and characterize the disease precisely. These tests can also serve prognostic purposes and are useful for follow-up of myeloma patients. Molecular analyses remain pivotal for defining high-risk myeloma and are used in updated patient stratifications, while minimal residual disease assessment via flow cytometry, molecular techniques and radiological approaches provides additional prognostic information on patients' long-term outcome. This pivotal information will guide our future treatment decisions in forthcoming clinical trials. The European Myeloma Network group updated their guidelines on different diagnostic recommendations, which should be of value to enable appropriate use of the recommendations both at diagnosis and during follow-up.
Topics: Multiple Myeloma; Practice Guidelines as Topic
PubMed: 30171031
DOI: 10.3324/haematol.2018.189159 -
Genome Biology Oct 2016We introduce the Microenvironment Cell Populations-counter (MCP-counter) method, which allows the robust quantification of the absolute abundance of eight immune and two...
We introduce the Microenvironment Cell Populations-counter (MCP-counter) method, which allows the robust quantification of the absolute abundance of eight immune and two stromal cell populations in heterogeneous tissues from transcriptomic data. We present in vitro mRNA mixture and ex vivo immunohistochemical data that quantitatively support the validity of our method's estimates. Additionally, we demonstrate that MCP-counter overcomes several limitations or weaknesses of previously proposed computational approaches. MCP-counter is applied to draw a global picture of immune infiltrates across human healthy tissues and non-hematopoietic human tumors and recapitulates microenvironment-based patient stratifications associated with overall survival in lung adenocarcinoma and colorectal and breast cancer.
Topics: Adenocarcinoma; Adenocarcinoma of Lung; Biomarkers, Tumor; Breast Neoplasms; Cell Tracking; Colorectal Neoplasms; Computational Biology; Female; Gene Expression Profiling; Humans; Lung Neoplasms; RNA, Messenger; Stromal Cells; Transcriptome; Tumor Microenvironment
PubMed: 27765066
DOI: 10.1186/s13059-016-1070-5