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PubMed1993

Prediction of sudden cardiac arrest: risk stratification by anatomic substrate.

The prognostic importance of coronary artery anatomy to specific outcomes including ventricular tachycardia/fibrillation was evaluated in 372 consecutive patients undergoing cardiac catheterization at University Hospital at Stony Brook between 1981 and 1984. The hypothesis that proximal left anterior descending artery narrowing before the first septal perforator had a specific relationship to survival was again tested in this cohort. The population was prospectively followed for 8 years, with all clinical management decisions made independently by the patient's primary or referring physician. Multivariate statistical and life table analyses were performed after comprehensive follow-up. Significant narrowing in the proximal left anterior descending artery was associated with an increased risk of sudden cardiac death (p = 0.0002). Abnormalities of contractility in the diaphragmatic segment of the left ventricle in addition to an elevation of the left ventricular end-diastolic pressure and the presence of congestive heart failure (p < 0.05) were other contributory variables. Outcome in patients with proximal left anterior descending coronary artery disease who underwent aortocoronary artery bypass to the artery demonstrated improved survival (p < 0.05). Risk stratification of patients at high risk for sudden cardiac death is possible and may allow identification for an aggressive approach or interventional trials.

Adult↗
PubMed2003

Prognostic significance of metastatic lymph node size in patients with gastric cancer.

BACKGROUND: Patients with gastric cancer that has metastasized to the lymph nodes are a heterogeneous population with a variable prognosis. Stratification of these patients into prognostic groups is necessary for optimal adjuvant therapy. METHODS: The study comprised 715 patients who had undergone curative resection of a gastric neoplasm. Lymph nodes were sectioned, stained with haematoxylin and eosin, and the diameter of the largest metastatic lymph node (MLN) was measured. Patients with metastatic nodes were divided into groups n1 and n2 according to the size of the MLN. The cut-off level was set at 7 mm by a two-sample log rank test; patients in group n1 had a MLN size of 7 mm or less and those in group n2 had a MLN of 8 mm or more. RESULTS: Patients were stratified into significant prognostic groups by both the Union International Contra la Cancrum (UICC) node (N) stage and MLN size (n group). The UICC N-stage subcategories were further divided into prognostic groups according to MLN size (n group). On multivariate analysis the MLN size remained independently significant in terms of overall and disease-free survival rates, and the UICC N stage was not significant, independently of the n group. Node-positive patients with fewer than 15 lymph nodes removed at operation could also be stratified into prognostic groups by the n group. Stratification according to the TNM stage and by MLN size was superior to existing UICC TNM staging. CONCLUSION: This new method may help clinicians to design a more appropriate treatment strategy for patients with gastric cancer.

Adult↗
PubMed1994

Noninvasive Coronary Risk Stratification of Elderly Patients.

The prognostic value of stress thallium-201 myocardial perfusion imaging has not been defined in an elderly (at or above 70 years) population. To this end, we studied 468 consecutive elderly patients undergoing either Bruce protocol exercise stress (n equals 120) or intravenous dipyridamole stress (n equals 348) with quantitative planar thallium-201 imaging. These patients were followed for at least 2 years after testing to determine their rates of cardiac events (cardiac death, myocardial infarction, coronary revascularization). There were no stress-related complications in either subgroup. A 10% cardiac event rate (6 deaths and 6 myocardial infarctions) was observed in the exercise subgroup. Survival without cardiac events was associated with greater exercise duration (5.6Â+/-2.4 vs 3.1Â+/-2.4 min; P is less than 0.001) and peak exercise heart rate (131Â+/-18 vs 120Â+/-19 bpm; P is less than 0.05). Multivariate analysis identified the combination of peak exercise at or below Stage 1 and thallium-201 perfusion defects as significant predictors of cardiac events (relative risk equals 5.3 at 1 year). Sixty-four percent of elderly patients were successfully stratified into very low and high risk subgroups, with annual cardiac event rates of less than 1% and greater than 15%, respectively. The cardiac event rate in dipyridamole stress patients was 22% (24 myocardial infarction, 52 death, 42 revascularization). The cardiac event rate was significantly lower (5%) in 150 patients with a normal dipyridamole thallium-201 study (P is less than 0.001). Clinical univariate predictors of cardiac events were previous myocardial infarction, congestive heart failure symptoms, hypercholesterolemia and diabetes (all P equals 0.05). A fixed, reversible, or combined thallium defect pattern was correlated with cardiac death or myocardial infarction (P is less than 0.05). Multivariate analysis demonstrated that the presence of an abnormal dipyridamole thallium study was the single-best predictor of cardiac events (relative risk equals 7.2; P is less than 0.01) We conclude that exercise and dipyridamole thallium-201 myocardial imaging are powerful independent noninvasive techniques for prognostication in the elderly patient population, a group with the potential for advanced coronary artery disease and a high risk of cardiac events.

Journal Article↗
PubMed2005

Risk stratification after radical prostatectomy in men with pathologically organ-confined prostate cancer using volume-weighted mean nuclear volume.

OBJECTIVE: We examined the impact of volume-weighted mean nuclear volume (MNV) on biochemical failure after radical prostatectomy (RP) in pathologically organ-confined prostate cancer (PC) and developed a prognostic factor-based stratification model for these patients. PATIENTS AND METHODS: We analyzed 141 patients with pathologically organ-confined PC treated solely with RP. Unbiased estimates of MNV were calculated from biopsy specimens based on a stereological method, and compared with other clinical and pathologic findings including patient age, pre-treatment PSA, biopsy and RP specimen Gleason score, pathologic stage, total cancer volume, index cancer volume, tumor differentiation, number of tumor foci, main tumor location, and surgical margin status, with regard to prediction of disease outcome after RP using Cox proportional hazard models. RESULTS: The median follow-up was 38.6 months (range 4--119 months). Twenty patients (14.2%) experienced biochemical failure. On multivariate analysis, MNV was demonstrated to be an independent prognostic factor, along with pre-treatment PSA and total cancer volume (P=0.0004, 0.0184, and 0.0285, respectively). All patients were stratified into three groups according to their prognostic scores developed on the basis of multivariate analysis, with statistically significant prognostic differences revealed for each of the between-group comparisons. CONCLUSION: The results demonstrated that estimates of MNV contribute most significantly to the prediction of biochemical control of pathologically organ-confined PC. The combination of MNV with other independent predictors such as pre-treatment PSA and total cancer volume provided a statistically verifiable basis for risk stratification, facilitating more accurate prediction of disease outcome.

Aged↗
PubMed2004

Gene expression profiles and risk stratification in childhood acute lymphoblastic leukemia.

BACKGROUND AND OBJECTIVES: Childhood acute lymphoblastic leukemia (ALL) is a heterogeneous disease. There are several distinct genetic subtypes, characterized by typical changes in gene expression pattern. In addition to cytogenetic markers, the in vivo response to treatment is an emerging prognostic marker for risk stratification. However, it has not yet been reported whether gene expression profiles can predict risk group stratification already at the time of diagnosis. DESIGN AND METHODS: We analyzed bone marrow samples of 31 ALL patients to identify changes in gene expression that are associated with the current risk assignment, irrespective of the genetic subtype. Gene expression profiles were established using oligonucleotide microarrays. RESULTS: Considering all low- and high-risk patients, no gene was capable of predicting the risk assignment already at time of diagnosis. However, screening for risk group associated genes using more homogeneous subsets of patients revealed 10(6) discriminatory probe sets. The prognostic significance of these probe sets was subsequently determined for the entire series of patients. Using the selected subgroups as the training set and the remaining samples as an independent test set, logistic regression using 3 predictor variables could accurately predict current risk assignment for 10 out of 12 patients. INTERPRETATION AND CONCLUSIONS: Gene expression profiles established from a cytogenetically heterogeneous study group are not, as yet, sufficiently accurate to be used prognostically in a clinical setting. Additional risk-associated gene expression analyses need to be performed in more homogeneous sets of patients.

Child↗
PubMed2001

Expression of a single gene, BCL-6, strongly predicts survival in patients with diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is characterized by a marked degree of morphologic and clinical heterogeneity. Establishment of parameters that can predict outcome could help to identify patients who may benefit from risk-adjusted therapies. BCL-6 is a proto-oncogene commonly implicated in DLBCL pathogenesis. A real-time reverse transcription-polymerase chain reaction assay was established for accurate and reproducible determination of BCL-6 mRNA expression. The method was applied to evaluate the prognostic significance of BCL-6 expression in DLBCL. BCL-6 mRNA expression was assessed in tumor specimens obtained at the time of diagnosis from 22 patients with primary DLBCL. All patients were subsequently treated with anthracycline-based chemotherapy regimens. These patients could be divided into 2 DLBCL subgroups, one with high BCL-6 gene expression whose median overall survival (OS) time was 171 months and the other with low BCL-6 gene expression whose median OS was 24 months (P =.007). BCL-6 gene expression also predicted OS in an independent validation set of 39 patients with primary DLBCL (P =.01). BCL-6 protein expression, assessed by immunohistochemistry, also predicted longer OS in patients with DLBCL. BCL-6 gene expression was an independent survival predicting factor in multivariate analysis together with the elements of the International Prognostic Index (IPI) (P =.038). By contrast, the aggregate IPI score did not add further prognostic information to the patients' stratification by BCL-6 gene expression. High BCL-6 mRNA expression should be considered a new favorable prognostic factor in DLBCL and should be used in the stratification and the design of risk-adjusted therapies for patients with DLBCL. (Blood. 2001;98:945-951)

Adolescent↗
PubMed1982

Pulse methylprednisolone in SLE.

Insufficient information is available about the effectiveness of high-dose intravenous corticosteroid treatment in non-renal SLE to determine whether it provides better management of the disease. Issues of steroid preparation, dose and frequency have not been addressed. Significant short-term complications appear to be minimal; the question of long-term effects on avascular necrosis may not be answerable since most patients also receive oral corticosteroids at some time during their course. No large randomized controlled trial of pulse IV-MP in lupus nephritis is available. Ideally, such a trial would include randomization with stratification according to important prognostic variables. Previous studies of other agents have been hampered by lack of agreement about both the identification of relevant prognostic variables and the selection of 'significant' measures of outcome. The observation that patients with recent deterioration in glomerular filtration rate are more likely to improve after IV-MP may form the basis for stratification in a controlled trial of the comparative efficacy of IV-MP and other forms of treatment. However, lack of improvement in glomerular filtration rate among patients without recent deterioration in function may reflect the inadequacy of our outcome measures rather than a true lack of beneficial effect for the patient.

Bacterial Infections↗
PubMed1998

Incremental prognostic value of myocardial perfusion single photon emission computed tomography for the prediction of cardiac death: differential stratification for risk of cardiac death and myocardial infarction.

BACKGROUND: The incremental prognostic value of stress single photon emission computed tomography (SPECT) for the prediction of cardiac death as an individual end point and the implications for risk stratification are undefined. METHODS AND RESULTS: We identified 5183 consecutive patients who underwent stress/rest SPECT and were followed up for the occurrence of cardiac death or myocardial infarction. Over a mean follow up of 642+/-226 days, 119 cardiac deaths and 158 myocardial infarctions occurred (3.0% cardiac death rate, 2.3% myocardial infarction rate). Patients with normal scans were at low risk (< or =0.5%/y), and rates of both outcomes increased significantly with worsening scan abnormalities. Patients who underwent exercise stress and had mildly abnormal scans had low rates of cardiac death but higher rates of myocardial infarction (0.7%/y versus 2.6%/y; P<.05). After adjustment for prescan information, scan results provided incremental prognostic value toward the prediction of cardiac death. The identification of patients at intermediate risk of nonfatal myocardial infarction and low risk for cardiac death by SPECT may result in significant cost savings when applied to a clinical testing strategy. CONCLUSIONS: Myocardial perfusion SPECT yields incremental prognostic information toward the identification of cardiac death. Patients with mildly abnormal scans after exercise stress are at low risk for cardiac death but intermediate risk for nonfatal myocardial infarction and thus may benefit from a noninvasive strategy and may not require invasive management.

Adenosine↗
PubMed1991

Stratification of multiple myeloma according to serum beta 2-microglobulin and serum albumin levels.

In 71 patients with multiple myeloma the authors evaluated the clinical significance and the prognostic relevance of Bataille's stratification system based on serum beta 2-microglobulin and serum albumin levels. This staging system, which classified the patients to low, intermediate and poor risk groups (stages 1-3) showed a rather small prognostic significance, and it stratified our myeloma patients unsatisfactorily. On the basis of the results of our own analyses, we have developed our own modification of a pilot stratification system. We have verified its good clinical applicability and its powerful prognostic prediction. In this study, the good prognostic significance of serum beta 2-microglobulin and albumin levels (with the best cut-off levels of 4.0 mg/l and 35.0 g/l) and a good correlation between both analysed markers were confirmed.

Adult↗
PubMed1991

The relationship between survival and the extent of the resection in patients with supratentorial malignant gliomas.

Current neurosurgical opinion favors the radical surgical removal of supratentorial gliomas, when feasible, in the belief that this optimizes patient survival. Although bolstered by the results of some early investigators, the efficacy of this approach remains debatable. Therefore, we undertook a review of the English language literature of the past 30 years for a series of surgically treated malignant gliomas. Twenty reports comprising 5691 patients were identified. Only 4 found the extent of the surgical resection related to survival. In 2 of these, it followed age, histological findings, and performance status in importance. The 2 other studies did not rank the prognostic variables at all. On closer inspection, however, there does appear to be a subgroup of young patients with favorable histological findings and good performance status for whom surgery is beneficial. Future reporting of surgical results of patients with gliomas will require stratification by the known prognostic variables of age, histological findings, and performance status to characterize better this subgroup for whom surgery is beneficial.

Age Factors↗
PubMed2003

Practical applications in stress echocardiography: risk stratification and prognosis in patients with known or suspected ischemic heart disease.

OBJECTIVES: The purpose of this study was to define appropriate parameters for risk stratification and prognosis in patients undergoing stress echocardiography. BACKGROUND: Stress echocardiography is an established technique for the diagnosis of coronary artery disease. However, current data on risk stratification of patients undergoing stress echocardiography are limited. METHODS: We evaluated 1,500 patients (59 +/- 13 years old; 51% male) undergoing stress echocardiography (34% with treadmill exercise and 66% with dobutamine). Resting left ventricular ejection fraction (EF) and regional wall motion were assessed by the consensus of two echocardiographers. Follow-up (mean 2.7 +/- 1.0 years) for confirmed non-fatal myocardial infarction (n = 31) and cardiac death (n = 44) were performed. RESULTS: By univariate analysis, both the peak wall motion score index (WMSI) (p < 0.0001) and EF (p < 0.0001) were significant predictors of cardiac events. Peak WMSI effectively risk stratified patients into low (0.9%/year), intermediate (3.1%/year), and high (5.2%/year) risk groups (p < 0.0001). A threshold of 45% EF provided further risk stratification of all WMSI groups. By multivariate logistic regression analysis, peak WMSI (relative risk [RR] 2.1, 95% confidence interval [CI] 1.0 to 4.4; p = 0.04) and EF (RR 1.0, 95% CI 0.9 to 1.0; p = 0.01) were both predictors of cardiac events. CONCLUSIONS: Stress echocardiography yields prognostic information for risk stratification of patients with known or suspected ischemic heart disease. A normal stress echocardiographic study (peak WMSI = 1.0) confers a benign prognosis (0.9%/year cardiac event rate). Peak WMSI >1.7 and EF < or =45% are independent markers of patients at high risk of an adverse clinical outcome.

Echocardiography, Stress↗
PubMed2006

[Prediction value for operative mortality of four different coronary artery bypass graft risk stratification models in Chinese patients].

OBJECTIVE: To assess the prognostic accuracy for operative mortality of 4 different risk stratification models in Chinese patients underwent (coronary artery bypass graft) CABG. METHODS: Between 2002 and 2003, all patients undergoing CABG in our institution were prospectively scored for operative mortality using Parsonnet, EuroSCORE, Cleveland and OPR scoring systems and operative mortality was registered. Operative mortality is defined as postoperative death of any cause during hospitalization. Calibration was estimated using the Hosmer-Lemeshow goodness-of-fit test. Discrimination was evaluated using receiver operating characteristic (ROC) curves and area under a ROC curve (AUC). RESULTS: Follow-up was able to be completed in 2251 prospectively scored patients. Registered operative mortality was 1.87% (42/2251). The overall expected mortality calculated by Parsonnet, EuroSCORE, Cleveland and OPR scoring systems were 5.78%, 2.82%, 3.30% and 1.65%, respectively. The actual operative mortality was within the range of 95% confidence interval of OPR model and the other 3 predicted significantly higher operative mortality. Among the four risk scores, Calibration was good in OPR model (chi(2) = 4.842, P = 20.182) and poor in other 3 models (P < 0.001) while discrimination was acceptable in Parsonnet, Cleveland and OPR scoring systems (AUC: 0.711, 0.754, 0.757, respectively) and excellent in EuroSCORE scoring system (0.813). CONCLUSION: For Chinese patients undergoing CABG, OPR scoring system best predicted the operative mortality. All systems could be used to discriminate operative mortality for individual patient.

China↗
PubMed1994

The additional prognostic value of morphometric nuclear arrangement and DNA-ploidy to other morphometric and stereologic features in endometrial hyperplasias.

Earlier studies have shown that morphometric analysis of nuclear size and shape features and stereologic analysis of gland architecture in endometrial hyperplasia are useful to predict the risk of progression to cancer. A multivariate discriminatory D-score using these features has a higher sensitivity than qualitative microscopic characteristics (nuclear atypicality and glandular complexity) when an appropriate threshold is chosen. In the present study, the (additional) prognostic value of morphometric features related to the arrangement of nuclei in glands (distance of nuclear centroids to basal membrane, angle of longest nuclear axis with basal membrane) and DNA-ploidy (determined by flow cytometry) has been analyzed in 39 cases of endometrial hyperplasia, seven (18%) of which have progressed to cancer. Variation in stratification of nuclei has prognostic value, in contrast to DNA-ploidy. Multivariate analysis selects the outer surface density of the glands, mean distance, volume percentage of lumen and the coefficient of variation of nuclear axes as having separate and additional value. A multivariate rule called HYPER-score results from these features. With this score a high-risk (score value >/=0.20, nine cases, 78% progressed) and a low-risk group (score value <0.20, 30 cases, none progressed) can be discerned. The prognostic value, sensitivity and specificity of the hyper-score greatly exceeds that of any of the previously described prognostic factors in endometrial hyperplasias. An additional clinical advantage is that with the HYPER-score two groups (instead of four groups as with Kurman's method(1)) with a high sensitivity and specificity can be discerned. The morphometric and stereologic features agree well with the usual qualitative predictors but have much stronger prognostic value.

Journal Article↗
PubMed1996

Intensive treatment of patients age 60 years and older with de novo acute myeloid leukemia: analysis of prognostic factors.

BACKGROUND: This study aimed to define pre-treatment parameters with prognostic significance in elderly patients with de novo acute myeloid leukemia (AML) who were treated with aggressive regimens. METHODS: We analyzed, retrospectively, the clinical and laboratory features of 159 consecutive patients age >60 years with AML. Ninety-two patients presenting as de novo AML were considered suitable for aggressive chemotherapy according to inclusion criteria not different from those commonly used for younger adults. They belonged to all of the French-American-British classification types except M3, and their median age was 67 years (range: 60-79). Antileukemic treatment consisted of 1 of 3 sequential protocols adopted at the S. Eugenio University Hospital of Rome between 1987 and 1993. The three therapeutic groups were similar in number and presenting characteristics. In addition to arabinosylcytosine, induction schedules included mitoxantrone (Groups I and II) or daunorubicin (Group III), and etoposide (Groups I and III). Once in complete remission (CR), patients were consolidated with two other courses of chemotherapy using reduced dosages of the same drugs given during induction. RESULTS: Induction treatment achieved a 52.2% CR rate, with median remission duration and event free survival (EFS) of 35 and 27 weeks, respectively. Because no significant differences between the results of the three therapeutic groups were observed, all cases were pooled to evaluate the prognostic factors. In univariate analysis, the only presenting characteristic significantly associated with failure of induction treatment was age >67 years (P=0.007). Factors associated with an increased likelihood of shorter remission duration were CD7 expression on leukemic cells (P=0.007) and an abnormal karyotype (P=0.010; those predicting shorter EFS were a chromosomal status other than normal (P=0.002) and detection of CD14 antigen (P=0.008). Logistic regression results identified age and CD14 expression as the variables with independent prognostic impact on CR achievement. In a stepwise proportional hazards general linear model, CD7 and karyotype retained their predictive value regarding remission duration, whereas the karyotypic pattern at diagnosis and CD14 antigen expression were the most important determinants of EFS, with age showing a borderline statistical value. A simple "risk factor score" was developed that would allow for stratification of patients into prognostic groups. CONCLUSIONS: Cytogenetic analysis and immunophenotyping might help to select elderly patients with AML who have little benefit from current therapeutic strategies and with whom new approaches might be experimented.

Acute Disease↗
PubMed1995

Prognostic factors for survival in patients with metastatic renal cancer treated with biological response modifiers.

PURPOSE: Clinical characteristics prognostic of survival in patients with metastatic renal cell carcinoma treated with biological response modifiers are poorly understood. Understanding these prognostic features may help with better stratification of patients in clinical trials and define further appropriate treatment for each prognostic subgroup. MATERIALS AND METHODS: A retrospective study of 84 patients with recurrent or metastatic renal cancer was conducted to identify prognostic factors for survival in patients who received biological response modifiers (alpha-interferon, beta-interferon, gamma-interferon and interleukin-2). RESULTS: Univariate analysis identified Eastern Cooperative Oncology Group (ECOG) performance status (1 versus 0, p < 0.001), bone metastasis (p = 0.008), recent weight loss (greater than 10% of total body weight versus no loss, p = 0.028), history of nephrectomy (no versus yes, p = 0.025), recurrence at the renal bed (p = 0.043) and sarcomatoid histology (yes versus no, p < 0.001) as important prognostic indicators. Multivariate analysis of prognostic factors in this patient population indicated that ECOG performance status, sarcomatoid histology and bone metastasis were most significant, while other factors were less significant (p > 0.05) after adjusting for ECOG performance status and sarcomatoid histology. Based on the total positive number of 5 risk factors defined previously the study population separates into 3 risk groups, with a median survival from the low to high risk groups of 14.4, 10.9 and 1.3 months, respectively. Prognostic scores based only on ECOG performance status, sarcomatoid histology and bone metastasis allowed for stratification of our patients into 3 distinct groups with median survivals of 18.6, 8.4 and 3.8 months, which were also predictive of survival (p < 0.05). CONCLUSIONS: Risk factors of ECOG performance status, sarcomatoid histology, bone metastasis, history of nephrectomy, recent weight loss and recurrence at the renal bed are predictive of survival in patients treated with biological response modifiers. In addition to previous findings of prognostic factors in renal cancer patients treated with chemotherapy, we identified sarcomatoid histology as an important risk factor in patients treated with biological response modifiers.

Bone Neoplasms↗
PubMed1994

Base of skull chordoma. A correlative study of histologic and clinical features of 62 cases.

BACKGROUND: Chordomas are uncommon primary malignant tumors of bone that typically occur in the axial skeleton including the sacrum, vertebrae, and skull base. The base of skull tumors usually are not amenable to complete surgical resection, and most require postoperative radiotherapy. The natural history of skull base chordoma is typified by slow locally invasive tumor progression and eventual death, although few parameters are known that allow stratification of patients into prognostic groups. METHODS: Sixty-two patients with skull base chordomas treated at the Massachusetts General Hospital by proton beam irradiation therapy with at least 2 years of follow-up information were reviewed in an attempt to identify clinical and pathologic parameters that predicted outcome. RESULTS: Female sex, tumor necrosis in preradiation treatment biopsy, and tumor volume in excess of 70 ml were each independent predictors of shortened overall survival after radiation therapy for skull base chordoma. CONCLUSIONS: Stratification of patients with skull base chordoma into poor and good outcome groups can be performed using the three parameters identified in our study. In addition, the striking difference in survival between the sexes suggests that further investigations of these tumors should include determination of their hormonal receptors status and consideration of hormonal manipulation in their management.

Adult↗