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Results for “prognostic stratification”

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PubMed2005

Molecular heterogeneity and prognostic biomarkers in adults with acute myeloid leukemia and normal cytogenetics.

PURPOSE OF REVIEW: Patients with acute myeloid leukemia (AML) and normal karyotype constitute the single largest cytogenetic group of AML, estimated to account for 45% of adults with de novo AML. This article critically reviews the recent literature that addresses the molecular heterogeneity of this group of patients and how this relates to prognostic stratification and novel therapeutic approaches. RECENT FINDINGS: Four prognostic biomarkers-the internal tandem duplication and point mutations in the FLT3 gene, partial tandem duplication of the MLL gene, mutations of the CEBPA gene, and overexpression of the BAALC gene-have been found to predict outcome in patients with AML and normal cytogenetics. In addition, one study using gene expression profiling identified two subgroups of AML patients with a normal karyotype whose survival differs significantly. Because mutations in FLT3 result in an autophosphorylated, leukemogenesis-driving protein, molecular targeting therapy with a new class of tyrosine kinase inhibitors is being explored in early clinical trials. SUMMARY: Considerable progress has been made in molecular characterization of AML patients with normal cytogenetics. The challenge for the future is to incorporate these biologic discoveries into novel risk-adapted therapeutic strategies that will improve the currently disappointing cure rate (approximately 25-40%) of this group of patients.

Adult↗

PubMed2006

International Staging System required standardization of biochemical laboratory testing in multiple myeloma.

The standardization of biochemical measurement procedures in multiple myeloma is necessary for reliable prognostic stratification of patients in multicentric trials. The new prognostic index International Staging System for multiple myeloma uses only two laboratory markers, albumin and beta-2 microglobulin. Our study compared results of albumin, beta-2 microglobulin and monoclonal immunoglobulin measurements from six centers which provide treatment for multiple myeloma in the Czech Republic and attempted to standardize the analytic procedures. We have found that the measurement of albumin is well standardized and the results from all laboratories were comparable. The measurement of beta-2 microglobulin achieved comparability only after a partial unification of analytical methods. The determination of monoclonal immunoglobulin concentration provided comparable results for concentrations higher than 20 g/l with higher variability for lower values.

Antibodies, Monoclonal↗

PubMed2004

Microvessel density compared with the Chalkley count in a prognostic study of angiogenesis in breast cancer patients.

AIMS: Evaluation of angiogenesis by intratumoral vessel profiles can be performed by different methods. The aim of this study was to investigate the prognostic value of estimates obtained by the intratumoral microvessel density (MVD) method and then to compare with corresponding estimates obtained by the Chalkley method. METHODS AND RESULTS: A total of 330 patients treated for primary, unilateral, invasive breast carcinoma were included. The median follow-up time was 14 years and 4 months. The microvessels were immunohistochemically stained by antibodies to CD34. MVD was not significantly correlated with any clinicopathological variables. By univariate analysis, MVD showed no prognostic value with regard to recurrence-free survival (RFS) or overall survival (OS), while the Chalkley count had significant prognostic value (P < 0.0001; RFS and OS). In the Cox multivariate analysis, MVD had no prognostic impact [median HR [confidence interval (CI)] was 0.93 [0.66, 1.32] for RFS; and HR [CI] was 0.86 [0.62, 1.19] for OS], while the Chalkley count [median HR (CI) was 2.12 (1.48, 3.06) for RFS; and HR (CI) was 1.71 (1.23, 2.37) for OS] provided independent prognostic value when adjusted for age, menopausal status, axillary lymph node status, tumour size, histological grade, adjuvant systemic treatment and radiation therapy. In comparing the results obtained by MVD in our study with those from other published studies we find good agreement. CONCLUSIONS: The Chalkley count technique seems to be preferable for estimating angiogenesis with regard to the prognostic stratification of breast cancer patients, based on its strong prognostic impact, and acceptable reproducibility.

Age Distribution↗

PubMed2004

TNM and Japanese staging systems for gastric cancer: how do they coexist?

Two staging systems for gastric cancer, International Union Against Cancer (UICC)/TNM and the Japanese classification, have been used widely for clinical practice and research. The two systems started independently in the 1960s, and underwent several revisions and amendments in order to approach each other, but have become more divergent in the latest editions because of characteristics based on different philosophies. The TNM system adopted a number-based system for N-staging that provides easy and accurate prognostic stratification. Comparative studies have shown that the TNM system has greater prognostic power than the Japanese classification. It contains, however, no treatment guidance and should primarily be used as a guide to prognosis. In contrast, the Japanese classification has been designed as a comprehensive guide to treatment, originally for surgeons and pathologists, and today for oncologists and endoscopists as well. Its anatomical-based N-staging was established based on analysis of lymphadenectomy effectiveness, and naturally provides direct surgical guidance. Clinicians should understand the roles of each system and must not mix the systems or terminology when they report their study results.

Humans↗

PubMed1995

Prognostic Factors in Small Cell Lung Cancer.

Extent of disease and clinical performance status have been used traditionally for prognostic stratification of patients with small cell lung cancer. A plethora of other prognostic attributes reflecting host factors, tumor factors, and serological and hematological parameters have been described over the last decade. Attempts to assess the contribution of the latter attributes to prognostication in small cell lung cancer have lead to the formation of multivariate prognostic models. These models invariably describe prognostic groupings that are not identified by the conventional two-stage classification currently in use. Consensus for application of a new prognostic classification is evolving with analysis of prognostic data from diverse clinical centers.

Journal Article↗

PubMed2026

scRNA-seq and bulk RNA-seq reveal the characteristics of macrophage copper metabolism and establish a risk signature in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is a prevalent malignancy with an urgent need for improved prognostic stratification and treatment-response prediction. This study aimed to explore a macrophage copper metabolism-associated prognostic model and to investigate the relationship between this risk model and the tumor immune microenvironment. METHODS: The FindClusters function was used to analyze cell clusters, and CellChat and CellPhoneDB/LIANA were employed for cell-cell communication analysis. Copper metabolism-related genes were sourced from the MSigDB database. A prognostic risk model was established using least absolute shrinkage and selection operator (LASSO) analysis and multivariate Cox regression analysis, and a nomogram was constructed by integrating the prognostic model with clinicopathological factors. Additional analyses were performed to map the seven model genes in single-cell data, assess model uncertainty and robustness, evaluate macrophage/copper/cuproptosis-related transcriptional programs, and examine the correlations between risk score, immune infiltration and predicted drug sensitivity. RESULTS: Using single-cell RNA sequencing (scRNA-seq) data, we identified four macrophage subpopulations. Macrophages with high SPP1 expression showed close interaction with T cell populations and were associated with copper ion metabolism. By incorporating 141 copper metabolism-related genes and using The Cancer Genome Atlas Liver Hepatocellular Carcinoma (TCGA-LIHC) cohort, we constructed a seven-gene risk prediction model. Additional single-cell mapping showed that the model genes were detectable in the HCC single-cell dataset and showed a macrophage-associated expression pattern. The model showed moderate prognostic discrimination in TCGA-LIHC, whereas its external performance was heterogeneous and remained evaluable across external cohorts, with performance varying among datasets. Immune and mechanism-related analyses suggested that the risk signature was associated with macrophage-related infiltration, copper metabolism and cuproptosis-related transcriptional programs. Drug sensitivity analysis nominated Daporinad as a computationally predicted candidate compound, supporting Daporinad as a pharmacogenomic candidate for follow-up investigation. CONCLUSIONS: By integrating scRNA-seq and bulk RNA sequencing (RNA-seq) data, we constructed a macrophage copper metabolism-associated prognostic signature for HCC. The risk score was associated with survival, immune microenvironment features and predicted drug response, providing a transcriptomic framework for risk stratification and therapeutic hypothesis generation.

Hepatocellular carcinoma (HCC)↗

PubMed2006

Prospective validation of the Barcelona Clinic Liver Cancer staging system.

BACKGROUND/AIMS: The Barcelona Clinic Liver Cancer (BCLC) classification offers a prognostic stratification of patients with hepatocellular carcinoma (HCC). We recently demonstrated the BCLC's peculiar prognostic ability in a retrospective cohort of HCC patients. The aim of this study was to evaluate the BCLC system prospectively in a subsequent separate group of HCC patients enrolled at the same surgically oriented liver unit. METHODS: One hundred and ninety-five consecutive HCC patients were prospectively enrolled and their liver disease was staged before therapy. Unlike the BCLC treatment protocol, nodule size and number were not used as absolute exclusion criteria for radical treatment. Predictors of survival were identified using the Cox model. RESULTS: The median survival time was 23 months overall, and 53, 16, 7 and 3 months, respectively, for BCLC categories A, B, C, and D. In our cohort, BCLC had the best independent predictive power for survival when compared with the Okuda, CLIP, UNOS-TNM, and JIS prognostic systems (linear trend chi(2)=43.01, likelihood chi(2)=57.94, AIC 885.98). Moreover, the BCLC classification showed a better prognostic ability than the AJCC-TNM 2002 system in surgical patients. CONCLUSIONS: The discriminating power of BCLC staging was prospectively assessed in an Italian cohort of HCC patients treated mainly with radical therapies.

Adult↗

PubMed1998

Therapy of acute myeloid leukemia: towards a patient-oriented, risk-adapted approach.

BACKGROUND AND OBJECTIVE: The successful use of differentiating treatment for patients with acute promyelocytic leukemia (APL) suggests that other acute myeloid leukemias (AML) may benefit from tailored and subtype-specific therapy. Despite the fact that new drugs specifically targeting AML genetic lesions have not yet been developed, distinct karyotypic categories have been identified which may deserve differentiated treatment. In addition, molecular assays to assess response to therapy more sensitively are now available for several AML subsets. In this review, we discuss the role of genetic characterization in the therapy of AML, and the investigative efforts which we believe are still needed for the design of tailored treatment for each and every patient with this disease. DESIGN AND METHODS: The authors have been working in this field for many years and have contributed original papers, the data of which are incorporated in this article. In addition, the material analyzed in this overview includes articles and reviews covered by the Science Citation Index and Medline as well as some more recent unpublished personal observations. RESULTS: Modern therapeutic approaches to AML tend to differentiate post-induction treatment intensity according to cytogenetically defined risk categories. Such prognostic categorization is largely unsatisfactory. In fact, following the advent of newly developed molecular assays (e.g. RT-PCR and FISH), specific and prognostically relevant lesions are frequently found in patients with an apparently normal karyotype, and these patients are, therefore, re-assigned to more appropriate prognostic categories. In addition, recent studies suggest that some patients may benefit from an increase in induction intensity; rapid genetic characterization will be needed for future differentiation of initial therapy. However, preliminary investigation of AML by integrated karyotypic/molecular analyses show that no specific abnormalities are detectable in at least half of the cases. Therefore, use of genetic criteria for prognostic stratification is currently feasible in only a proportion of patients. INTERPRETATIONS AND CONCLUSIONS: The prognostic role of genetic lesions, currently identified by karyotypic studies, needs to be validated in large series of AML patients prospectively characterized by advanced molecular/cytogenetic analyses and treated uniformly. In addition, searches for new clinically relevant genetic abnormalities, and diagnostic tools for their rapid identification are urgently needed to identify prognostic categories better. Elucidation of AML gene alterations should foster basic investigation aimed at developing new drugs targeted to the specific lesion in the individual patient. Before these more specific therapeutic agents are developed, diagnostic genetic characterization should add to other well-established prognostic factors to optimize the use of the presently available therapies.

Acute Disease↗

PubMed1996

Estrogen and progesterone receptor status determined by the Ventana ES 320 automated immunohistochemical stainer and the CAS 200 image analyzer in 236 early-stage breast carcinomas: prognostic significance.

The quantitation of estrogen and progesterone receptors (ER and PgR) has become the standard of care in the evaluation of patients with primary breast carcinoma. It has been demonstrated that ER and PgR detected by immunohistochemical methods in formalin-fixed paraffin-embedded tissue can be quantified by computerized image analysis. In this study, ER and PgR levels were determined by using an automated immunochemistry stainer (Ventana ES 320) and an image analyzer (CAS 200) in a series of 236 patients with stage I/II carcinoma of the breast. The degree of correlation of the ER and PgR levels determined by the dextran-coated charcoal method (DCC) with image analysis quantitation was high (r=0.75). The agreement between both methods was 77% for ER and 73% for PgR. Hormone receptor levels were correlated with prognosis as determined by overall survival. An ER level of 30 fmol/mg as determined by image analysis was established to stratify the patient population most effectively into favorable and unfavorable prognostic groups (P=0.003). An ER level of 20 fmol/mg for prognostic stratification reached statistical significance (P=0.03). The DCC method was not able to stratify the patients into prognostic groups at the traditionally accepted cutpoint of 10 fmol/mg (P=0.52). We conclude that when used in combination, automated immunohistochemistry and quantitative image analysis offer a favorable alternative to the DCC method in assessment of ER and PgR status in human mammary carcinoma. In addition, quantitative immunocytochemistry techniques may prove superior to the DCC method in specimens in which there is limited tumor volume (including fine-needle aspirates), stroma-rich tumors, and early-stage lesions including intraductal carcinoma.

Aged↗

PubMed2005

Vascular calcification in patients with renal failure: culprit or innocent bystander?

The mortality from cardiovascular events in CKD and dialysis patients is substantially higher than in the general population. VC is ubiquitous and progresses rapidly in this patient population. Although there has been progress in the understanding of the pathogenesis and correlates of VC, much work needs to be done in this area. The role of calcium and, probably, phosphate (obligatory participants) is unquestionable, but the understanding of the paracrine and molecular determinants of VC in renal failure is continuously evolving. VC is probably a dynamic process resulting from the imbalance between molecules that promote and those that inhibit VC. The understanding of latter area has recently evolved with identification of new signaling pathways with molecules such as osteoprotegerin, fetuin-A, and MPG. From a clinical perspective, new modalities such as EBCT and MDCT allow noninvasive detection and quantification of VC. VC may represent a potential useful index for prognostic stratification and treatment planning in patients who have renal failure. At present, however, the data on the prognostic value of VC are available only in populations of patients who have normal renal function. Large-scale, prospective, observational studies should be designed to identify the determinants of VC and to define the prognostic role of calcium scoring in cohorts of patients who have predialysis CKD and with ESRD.

Atherosclerosis↗

PubMed1993

Very early risk stratification by electrocardiogram at rest in men with suspected unstable coronary heart disease. The RISC Study Group.

OBJECTIVES: To determine the possibility of very early prognostic stratification based on electrocardiograms (ECGs) at rest and/or cardiac enzyme levels after an episode of suspected unstable coronary heart disease. DESIGN AND SETTING: Men with suspected unstable angina or non-Q-wave myocardial infarction were studied in the coronary care units of eight hospitals. The ECGs at rest and creatinine kinase were followed. SUBJECTS: In total 911 men were followed for 12 months. Of 8136 consecutively admitted, 3365 fulfilled the inclusion criteria. Excluded were 2454 patients, mainly because of a larger myocardial damage, signs of myocardial dysfunction, other serious cardiac or non-cardiac disease or an ECG not possible to interpret regarding ST-T-segment changes in the precordial leads. MAIN OUTCOME MEASURES: End-points at follow-up were cardiac death, myocardial infarction and severe (class III or IV) angina. RESULTS: Compared to patients with normal a ECG who had an 8% 1-year risk of myocardial infarction or death, the risk with isolated negative T waves was 14% (P < 0.05), ST elevation 16% (P < 0.05), ST depression 18% (P < 0.01) and the combination of ST elevation and ST depression 26% (P < 0.001). The only finding related to future severe angina was ST depression. The risk of cardiac events was comparably elevated in patients with anterior or inferior site of ECG changes. Cardiac enzyme levels had no predictive value regarding future events. CONCLUSIONS: Electrocardiograms at rest obtained during the initial days of hospitalization provide very early and valuable prognostic information in men admitted with suspected unstable coronary heart disease.

Adult↗

PubMed2004

Molecular biology of sporadic gastric cancer: prognostic indicators and novel therapeutic approaches.

Both the availability of multiple treatment modalities and novel therapeutic targets make the correct prognostic stratification and the identification of truly predictive factors an issue of major debate in gastric cancer. Along with "classic" prognostic factors such as those related to the diffusion of the tumour at diagnosis (i.e., depth of gastric wall infiltration, locoregional lymph nodes or distant metastases) or those concerning the pathologic characteristics of the tumour, other, innovative, factors should be considered if a better definition of the characteristics of the tumour is to be given. These biological factors are often derived from the genetic process, which is thought to represent a crucial step to gastric cancer (DNA copy number changes, microsatellite instability, thymidilate synthase, E-cadherin, beta-catenin, mucin antigen, p53, c-erb B-2, COX-2, matrix metalloproteinases, VEGFR and EGFR). Some of those putative prognostic indicators can also be considered predictive of response to therapy as they are a molecular target either to chemotherapeutics (i.e., thymidilate synthase that is targeted by 5FU) or to a new class of antineoplastic molecules (i.e., c-erb B-2 targeted by trastuzumab, COX-2 by NSAIDs, matrix metalloproteinases, EGFR and VEGFR by specific inhibitors).

Apoptosis↗

PubMed2001

Elevated serum levels of soluble CD44 can identify a subgroup of patients with early B-cell chronic lymphocytic leukemia who are at high risk of disease progression.

BACKGROUND: Although soluble CD44 (sCD44) is considered a reliable marker of both tumor burden and disease activity, to the authors' knowledge, its predictive and prognostic value in B-cell chronic lymphocytic leukemia (CLL) has not been addressed to date. METHODS: The authors studied 94 previously untreated CD5-positive B-cell CLL patients whose sera was taken at the time of diagnosis, stored at - 70 degrees C, and analyzed for the presence of standard sCD44 (sCD44(std)) using a commercial enzyme-linked-immunoadsorbent-assay. The impact of the sCD44 level on the clinical outcome of the disease was assessed in 74 patients with early CLL (61 Binet Stage A patients and 13 asymptomatic Stage B patients). Because the time to disease progression appears to predict the survival time of patients with CLL, it was used as a surrogate endpoint in the current study. RESULTS: Patients with higher than median sCD44 levels (i.e., 642 ng/mL) had a more advanced clinical disease stage (P = 0.04), higher peripheral blood lymphocytosis (P = 0.006), and increased circulating levels of either lactate dehydrogenase (P = 0.01) or beta(2)-microglobulin (P < 0.0001). In univariate analysis, seven of the nine parameters investigated predicted progression-free survival (PFS). In a stepwise multiple regression analysis, only 2 parameters provided independent prognostic information regarding PFS: Rai substages (0 vs. I-II) (P = 0.002) and serum sCD44 levels > 642 ng/mL (P = 0.01). When added to the classification of smoldering CLL versus nonsmoldering CLL, the sCD44 level distinguished two groups within the group of nonsmoldering Stage A patients; patients with a sCD44 level > 642 ng/mL had a median PFS of 36 months, whereas patients with a sCD44 level < 642 ng/mL experienced a longer PFS (median had not been reached at 8 years of follow-up). Furthermore, serum levels of sCD44 defined two different patterns of PFS within the group of patients with Rai disease Stages I-II (P = 0.01). CONCLUSIONS: An increased serum level of sCD44 can be considered to be a promising parameter for predicting the risk of disease progression in patients with early CLL. Furthermore, sCD44 helps to refine the prognostic stratification of patients with either nonsmoldering CLL or Rai Stage I-II disease, thus enabling the identification of different prognostic subgroups in patients with early CLL.

Adult↗

PubMed1975

Assessment of 3-year prognosis in survivors of acute myocardial infarction.

A 3-year follow-up with regard to survival was made of 475 initial survivors of an acute myocardial infarction originally treated in a coronary care unit. Previous diseases, complications during the hospital stay, as well as findings recorded on discharge from hospital, were used to construct a prognostic stratification. By multivariate analyses maximum respiratory rate during the coronary care unit stay, left bundle-branch block, and age proved prognostically most important. Using only these factors, patient groups with a 3-year monthly mortality up to 74 per cent were characterized.

Age Factors↗

PubMed2026

Reduced VEPH1 expression is associated with an invasive phenotype and poor prognosis in clear cell renal cell carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) remains a clinically heterogeneous urologic malignancy, and improved biomarkers are needed to refine prognostic stratification. VEPH1 has been implicated in cancer biology, but its role in ccRCC is incompletely defined. This study aimed to investigate the expression, prognostic relevance, and functional effects of VEPH1 in ccRCC. METHODS: VEPH1 transcript expression and prognostic relevance were evaluated using The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) dataset and the University of Alabama at Birmingham Cancer Data Analysis Portal (UALCAN) and validated in paired ccRCC and adjacent normal renal tissues. The ability of VEPH1 transcript expression to distinguish tumor from normal tissues within the TCGA-KIRC dataset was assessed by receiver operating characteristic analysis. Gain- and loss-of-function experiments were performed in 786-O and 769-P ccRCC cells to determine the effects of VEPH1 on epithelial-mesenchymal transition (EMT)-related markers, migration, and invasion. AKT and ERK phosphorylation was evaluated by western blotting. RESULTS: VEPH1 transcript expression was significantly lower in ccRCC tissues than in normal renal tissues and distinguished tumor from normal samples within the TCGA-KIRC dataset. Low VEPH1 transcript expression was associated with poorer overall survival. Validation in 11 paired clinical specimens confirmed reduced VEPH1 messenger RNA (mRNA) and VEPH1 protein expression in tumor tissues. Functionally, VEPH1 overexpression increased E-cadherin, decreased N-cadherin, and suppressed migration and invasion, whereas partial VEPH1 knockdown produced the opposite changes. In exploratory signaling analyses, VEPH1 overexpression was associated with reduced AKT and ERK phosphorylation without altering total AKT or ERK levels. CONCLUSIONS: Reduced VEPH1 transcript expression was associated with poorer overall survival, whereas experimental VEPH1 depletion was associated with invasive and EMT-related features in ccRCC cells. VEPH1 may represent a candidate prognostic indicator in ccRCC; however, its relationship with AKT and ERK signaling and its clinical relevance require further mechanistic and independent-cohort validation.

Clear cell renal cell carcinoma (ccRCC)↗

PubMedDate not supplied

Chlamydia pneumoniae infection in patients with acute coronary syndrome: a clinical and serological 1-year follow-up.

The role of Chlamydia pneumoniae infection in pathogenesis and prognostic stratification of patients with acute coronary syndromes is still unclear. However, a limitation of many studies is the evaluation of the long-term prognostic role of a sample obtained during the acute phase, whereas the assessment of the temporal trend of antibody titers could be more useful. One-hundred and fourteen consecutive patients with acute coronary syndromes (71 with acute myocardial infarction and 43 with unstable angina) were studied. Blood samples were obtained immediately after hospital admission and 1, 3, 6 and 12 months after the acute event. The microimmunofluorescence test was used to detect C. pneumoniae specific antibodies. The incidence of new coronary events (death, myocardial infarction, recurrent angina) was recorded during the 1-year follow-up period. No significant difference was found between patients with (n = 35) or without (n = 79) new coronary events (N.C.E.) regarding baseline and serial values of C. pneumoniae antibodies. The rate of high titers at any time of follow-up was also similar in the two groups: IgG > or =1:512 were present in 52%, 64%, 55% and 32% of N.C.E.+ patients, and in 48%, 54%, 52% and 36% of N.C.E.- patients at 1, 3, 6 and 12 months respectively; IgA > or =1:256 were present in 26%, 23%, 30% and 23% of N.C.E.+ patients and in 20%, 30%, 25% and 19% of N.C.E.- patients at 1, 3, 6 and 12 months respectively. Our data indicate that elevated titers of C. pneumoniae antibodies, even with a serial 1-year evaluation, are not a predictor of future coronary events in patients with acute myocardial infarction or unstable angina.

Angina, Unstable↗

PubMed2026

Pretreatment EBV-DNA/TLG-Based Risk Stratification Is Associated With Survival Outcomes in Nonmetastatic Nasopharyngeal Carcinoma: An Exploratory Study.

Whether combining pretreatment plasma Epstein-Barr virus DNA (EBV-DNA) with 18F-FDG PET/CT-derived total lesion glycolysis (TLG) improves prognostic stratification in nonmetastatic nasopharyngeal carcinoma (NPC) is unclear, particularly in nonendemic populations. We retrospectively analyzed 86 eligible nonmetastatic NPC patients treated with definitive radiotherapy (2010-2024) at a single nonendemic-region institution. EBV-DNA (prespecified cutoff 3500 copies/mL) and TLG (cutoff 200, ROC-derived within this cohort) were dichotomized. Both were available in 59/86 patients (68.6%), who differed from the rest in nodal and overall stage and in RT technique. Baseline PET/CT was in-house in 57 of 86 patients, and a robustness analysis in that subgroup is reported. Given limited events (13 PFS, 9 OS), Cox analyses are exploratory and were supplemented with penalized regression and bootstrap validation. At a median follow-up of 75.5 months, 5-year PFS and OS for the whole cohort (n = 86) were 81.1% and 85.9%. The EBV-DNAhigh/TLGhigh subgroup remained associated with inferior PFS after adjustment in an exploratory model (adjusted HR = 3.97, 95% CI: 1.32-11.93) and, in a single-variable model, with inferior OS (HR = 4.13, 95% CI: 1.10-15.52). Discrimination was comparable to the individual-biomarker model for PFS and lower for OS. Five-year PFS fell monotonically across the four risk groups in the complete-case cohort (n = 59; 89.7%-58.3%). OS differed across groups (log-rank p = 0.044) but was not strictly monotonic, with wide, overlapping confidence intervals. This two-biomarker model is hypothesis-generating and needs prospective, multicenter validation before any consideration of risk-adapted treatment.

Epstein–Barr virus DNA↗

PubMed1991

The diagnostic and prognostic value of exercise electrocardiography in asymptomatic subjects and stable symptomatic patients.

In asymptomatic patients, the use of exercise ECG testing for the detection of subclinical coronary artery disease has considerable theoretical appeal, but its practical application is severely hampered by the constraints of Bayes' theorem. Serial exercise ECGs do not appear to offer significant improvement in this regard. Thallium-201 perfusion scintigraphy performed in conjunction with an exercise ECG can greatly improve the predictive value of such testing, although at considerable cost. Screening strategies with promise are those that reserve exercise testing for individuals at greater-than-average risk for subclinical coronary artery disease (eg, patients with multiple coronary risk factors) or that prescribe sequential testing, where only those with an abnormal exercise ECG are subjected to thallium-201 scintigraphy. At present, the optimal method of identifying asymptomatic individuals at high risk of a major cardiac event remains undefined. The use of maximal-effort stress testing has stood the test of time in the evaluation of patients with stable symptoms suggestive of coronary artery disease. This is particularly true when variables other than the ECG response to exercise are considered. The independent contribution of exercise angina remains controversial; however, recent studies indicate that it correlates with a more severe symptom pattern and more extensive coronary artery disease. Prognostic stratification in these studies was improved by considering both subjective and objective manifestations of ischemia. Although exercise ECG testing has been shown to have important prognostic value after acute myocardial infarction, exercise thallium-201 scintigraphy offers several potential advantages for asymptomatic post-myocardial infarction patients, several of which this paper reviews. The more optimal prognostic efficiency of thallium-201 scintigraphy is due in part to the fact that the error rate in falsely classifying patients at low risk is substantially smaller with scintigraphy than with stress electrocardiography. Because of this, there appears to be adequate rationale for recommending exercise perfusion imaging, rather than exercise ECG testing alone, as the preferred method for evaluating mortality and morbidity risks after acute myocardial infarction.

Coronary Disease↗