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The value of prognostic parameters for the stratification of advanced breast cancer patients.

One hundred seventy-five patients with metastatic breast cancer, treated with a combination chemotherapy (Cooper regimen), were analyzed retrospectively to identify the value of the traditional prognostic parameters (disease-free interval; menopausal status; dominant site of metastatic lesion) for the stratification of patients before randomization. Response rate and survival time were not significantly affected by the disease-free interval and menopausal status. A significant difference was detected among the three categories of dominant disease (locoregional; osseous; visceral). However, an estimate of total extent of disease (according to Swenerton) was found to be the most important factor for predicting response and survival time after combination cytotoxic treatment. The differences between the dominant size of metastatic disease are mainly influenced by different size of metastatic spread. Therefore, there is found a significant correlation between the different types of dominant lesions and total extent of disease. In conclusion, the particular sites of metastatic spread seem to be of less importance than overall extent of disease in predicting the outcome. A critical evaluation of the three traditional stratification parameters and introduction of a semiquantitative estimation of total tumor burden as a new stratification parameter seems to be necessary when planning and comparing future trials.

Adult↗

Prognostic significance of risk group stratification in elderly patients with acute myeloid leukaemia.

Prognostic factors were studied in a series of 211 acute myeloid leukaemia (AML) patients over 60 years of age, treated at a single centre. The patients were allocated into three risk groups based on cytogenetics, occurrence of antecedent haematological disorder and leucocyte count. Only 3% had low-risk features, 39% had intermediate- and 58% had adverse-risk features. Complete remission (CR) was achieved in 43% of all patients. In multivariate analyses, the number of cycles needed to achieve CR and the risk group were significantly associated with the duration of CR. Median survival time for the entire cohort of patients was only 107 d. Advanced age, low induction treatment intensity, treatment during earlier years and adverse-risk group were associated with shorter overall survival times. Risk group classification may help selection of elderly patients with a good chance of benefiting from intensive treatment to actually receive such treatment, while sparing others with a low probability of survival benefit from toxic treatment. Low intensity induction treatment reduces the chance of obtaining complete remission, produces inferior survival times and should consequently be avoided when the aim is to obtain complete remission. In elderly AML patients, introducing age and re-evaluation of intermediate and good prognosis patients regarding response to induction treatment may improve the risk group classification.

Acute Disease↗

Use of prognostic factors in risk stratification at diagnosis and time of treatment of patients with chronic lymphocytic leukemia.

PURPOSE OF REVIEW: To review risk stratification strategies used in chronic lymphocytic leukemia at diagnosis to predict aggressiveness of disease and, at time of treatment, to predict duration of response. RECENT FINDINGS: Several new prognostic factors can better assist clinicians in predicting the aggressiveness of chronic lymphocytic leukemia at diagnosis and the likelihood of maintaining a prolonged remission with treatment. This article reviews older prognostic factors such as beta2-microglobulin and thymidine kinase activity that have been partially validated by recently completed large studies. New prognostic factors such as interphase cytogenetics, immunoglobulin heavy-chain gene mutational analysis, and relevant secondary surrogate markers of immunoglobulin heavy-chain gene, including methylation of the zeta-associated protein gene, lipoprotein lipase overexpression, telomere length, and telomerase activity are reviewed. Some prognostic factors (interphase cytogenetics) but not others (immunoglobulin heavy-chain gene mutational status, zeta-associated protein expression) predict the duration of response to fludarabine-based combination strategies. SUMMARY: Recent advances in risk stratification provide clinicians with tools to better predict outcome of chronic lymphocytic leukemia at the time of treatment and response to treatment at the time of developing symptomatic disease.

Biomarkers, Tumor↗

Germinal center phenotype and bcl-2 expression combined with the International Prognostic Index improves patient risk stratification in diffuse large B-cell lymphoma.

The International Prognostic Index (IPI) identifies poor- and good-risk patients with diffuse large B cell lymphoma (DLBCL); however, the majority of patients have an intermediate IPI, with an uncertain prognosis. To determine whether cellular factors can be combined with the IPI to more accurately predict outcome, we have analyzed 177 presentation nodal DLBCLs for the expression of bcl-2 and a germinal center (GC) phenotype (defined by expression of bcl-6 and CD10). P53 gene band shifts were detected using single-stranded conformational polymorphism polymerase chain reaction analysis of exons 5-9 and were correlated with protein expression. In a Cox regression analysis, IPI (R = 0.22, P <.0001) and bcl-2 (R = 0.14, P =.0001) were independent poor prognostic factors and a GC phenotype predicted a favorable outcome (R = -0.025, P =.02). Neither p53 expression nor band shifts had a significant effect on survival. Using the IPI alone, 8% of patients were identified as high risk. Expression of bcl-2 in the intermediate IPI group identified a further 28% of patients with an overall survival comparable to the high IPI group. In the intermediate IPI, bcl-2(-) group, the presence of a GC phenotype improved overall survival to levels approaching the IPI low group. Following this analysis only 15% of patients failed to be assigned to a favorable- or poor-risk group. Sequential addition of bcl-2 expression and GC phenotype into the IPI significantly improves risk stratification in DLBCL. For the 36% of high-risk patients with a 2-year overall survival of 19%, alternative treatment strategies should be considered in future trials.

Adolescent↗

Prognostic-factors-based risk-stratification model for invasive urothelial carcinoma of the urinary bladder in Taiwan.

Objectives. To develop a prognostic-factors-based predictive model for invasive urothelial carcinoma of the urinary bladder derived from statistical comparison of clinical characteristics.Methods. The medical records for patients with invasive urinary bladder urothelial carcinoma were reviewed. Clinical data for age, sex, serum lactate dehydrogenase, creatinine, albumin, alkaline phosphatase, alanine aminotransferase, total bilirubin and hemoglobin levels, white blood cell and platelet counts, positive urine cytology, Eastern Cooperative Oncology Group performance status score, tumor size, histologic grading, T stage, presence of lymph node metastases, squamous differentiation, hydronephrosis, prostatic involvement, Charlson comorbidity index, surgical procedures, and adjuvant chemotherapy status were recorded. Univariate and multivariate analyses were performed to test independent factors for prediction of survival and disease recurrence.Results. After univariate and multivariate analyses, six independent prognostic factors were found: T stage, grading, prostatic involvement, Eastern Cooperative Oncology Group performance status score, and pretreatment serum creatinine and albumin levels. A scoring system was developed on the basis the relative risk associated with the proposed prognostic factors and patients were stratified into three groups according to their scores, with statistically significant prognostic differences revealed for each of the between-group comparisons. Independent factors affecting recurrence-free survival and best predicted disease recurrence were pretreatment serum creatinine, T stage, and surgical procedure.Conclusions. This prognostic-factors-based risk-stratification model for invasive urothelial carcinoma of the urinary bladder may help clinicians predict outcome and select the most appropriate therapeutic modalities. The incidence of recurrent disease is significantly higher for patients with poor renal function before treatment or advanced T stage and those undergoing transurethral tumor resection instead of radical cystectomy.

Aged↗

Survivin is an independent prognostic marker for risk stratification of breast cancer patients.

BACKGROUND: Results in previous qualitative studies of the association of the apoptosis inhibitor survivin with prognosis of breast cancer patients have been contradictory. METHODS: Survivin mRNA was measured by quantitative TaqMan reverse transcription-PCR in 275 breast cancer tissues from patients with operable tumors and was correlated with established clinicopathologic factors, relapse-free survival [(RFS); 102 events], and overall survival [(OS); 81 events]. RESULTS: High survivin mRNA concentrations were found mainly in tissues from younger patients and in high-grade cancer tissues. High survivin concentrations were most strongly associated with estrogen receptor- or progesterone receptor-negative tumors. In univariate Cox regression analysis for RFS, survivin concentrations were significantly associated with poor prognosis with a hazard ratio (HR) of 1.99 (95% confidence interval, 1.31-3.02; P = 0.001) for every 10-fold increase in expression. For OS, a significant contribution of survivin to poor prognosis was found with a HR of 2.76 (1.67-4.55; P <0.001). Multivariate analyses were performed including established clinicopathologic factors. For RFS, age (P = 0.027), nodal category (P <0.001), and survivin [HR = 1.78 (1.18-2.68); P = 0.006] contributed significantly to the model. For OS, only nodal category (P <0.001) and survivin [HR = 3.05 (1.83-5.10); P <0.001] were significant. CONCLUSION: Survivin demonstrates a strong, independent, association with poor prognosis. Survivin might be used as a new marker to stratify breast cancer patients for more optimal treatment modalities, or it could be a promising new target for therapy.

Biomarkers, Tumor↗

Validation of a new prognostic staging system for hepatocellular carcinoma: the JIS score compared with the CLIP score.

The Japan Integrated Staging score (JIS score), which combines the Child-Turcotte-Pugh classification and tumor-node-metastasis staging, has been proposed as a better prognostic staging system for hepatocellular carcinoma (HCC) than the Cancer of the Liver Italian Program (CLIP) scoring system. In this study, validation was performed among a larger patient population. A total of 4,525 consecutive patients with HCC who had been diagnosed at five institutions were included. Stratification ability, prognostic predictive power, and reproducibility were analyzed and compared with results from the CLIP scoring system. Only 45% (1,951 of 4,525) of all patients were categorized as early stage HCC according to JIS score (0 or 1), whereas 63% (2,878 of 4,525) of the patients were categorized as having a CLIP score of 0 or 1. Significant differences in survival curves were not observed among CLIP scores 3 to 6. In contrast, survival curves showed significant differences among all the JIS scores. The same JIS scoring subgroups showed a similar prognosis, and good internal reproducibility was observed in each of the institutions. Multivariate analysis of the prognosis in all 4,525 patients proved the JIS score to be the best prognostic factor. Furthermore, the Akaike information criteria proved that the JIS scoring system was statistically a better model for predicting outcome than the CLIP scoring system. In conclusion, the stratification ability and prognostic predictive power of the JIS score were much better than that of the CLIP score and were simple to obtain and remember.

Adult↗

Troponin T and quantitative ST-segment depression offer complementary prognostic information in the risk stratification of acute coronary syndrome patients.

OBJECTIVES: Our primary objective was to examine the prognostic relationship between baseline quantitative ST-segment depression (ST) and cardiac troponin T (cTnT) elevation. The secondary objectives were to: 1) examine whether ST provided additional insight into therapeutic efficacy of glycoprotein IIb/IIIa therapy similar to that demonstrated by cTnT; and 2) explore whether the time to evaluation impacted on each marker's relative prognostic utility. BACKGROUND: The relationship between the baseline electrocardiogram (ECG) and cTnT measurements in risk-stratifying patients presenting with acute coronary syndromes (ACS) has not been evaluated comprehensively. METHODS: The study population consisted of 959 patients enrolled in the cTnT substudy of the Platelet IIb/IIIa Antagonism for the Reduction of Acute coronary syndrome events in a Global Organization Network (PARAGON)-B trial. Patients were classified as having no ST (n = 387), 1 mm ST (n = 433), and ST > or =2 mm (n = 139). Forty-percent (n = 381) were classified as cTnT-positive based on a definition of > or =0.1 ng/ml. RESULTS: Six-month death/(re)myocardial infarction rates were 8.4% among cTnT-negative patients with no ST and 26.8% among cTnT-positive patients with ST > or =2 mm. On ECGs done after 6 h of symptom onset, ST > or =2 mm was associated with higher risk compared to its presence on ECGs done earlier (odds ratio [OR] 7.3 vs. 2.1). In contrast, the presence of elevated cTnT within 6 h of symptom was associated with a higher risk of adverse events compared with elevations after 6 h (OR 2.4 vs. 1.5). CONCLUSIONS: Quantitative ST and cTnT status are complementary in assessing risk among ACS patients and both should be employed to determine prognosis and assist in medical decision making.

Acetates↗

Risk stratification in chronic heart failure: independent and incremental prognostic value of echocardiography and brain natriuretic peptide and its N-terminal fragment.

BACKGROUND: It was the aim of this study to compare the prognostic impact of echocardiography and brain natriuretic peptide and its N-terminal fragment (NT-proBNP) in patients with chronic heart failure (CHF). METHODS: In all, 73 patients with CHF underwent conventional 2-dimensional/Doppler echocardiography and Doppler tissue analysis of systolic, early and late diastolic mitral annular velocities. The mitral filling pattern was classified as restrictive or nonrestrictive. NT-proBNP measurements were carried out on a bench-top analyzer. A cardiac event (rehospitalization caused by worsening CHF, cardiac death, urgent cardiac transplantation) was defined as combined study end point. RESULTS: During follow-up of 226 +/- 169 days, 27 patients had an event (rehospitalization because of CHF, n = 18; cardiac death, n = 7; urgent transplantation, n = 2). On multivariate Cox regression analysis, a restrictive filling pattern, NT-proBNP, the ratio of peak early diastolic mitral flow to mitral annular E' velocity were independent prognostic predictors. A risk stratification model based on the 3 strongest independent predictors separated groups into those with good, intermediate, and poor outcome (event-free survival of 78%, 46%, and 0%, respectively). CONCLUSIONS: In patients with CHF, Doppler echocardiography, Doppler tissue imaging, and NT-proBNP provide independent and incremental prognostic information. A combined use of echocardiography and NT-proBNP may help to improve risk stratification in this patient population.

Biomarkers↗

The changing role of the exercise electrocardiogram as a diagnostic and prognostic test for chronic ischemic heart disease.

The exercise electrocardiogram has been the subject of intense research over the last 50 years, as both a diagnostic and prognostic method to assess patients with chronic ischemic heart disease. In 1986, the strengths and limitations of the technique to predict coronary and multivessel disease in clinical patient subsets are understood. The diagnostic accuracy of the test is improved by consideration of Bayesian theory, multivariate models and new non-ST segment criteria. Post-test coronary disease risk estimates are best reported in terms of a conditional probability, rather than statements of "positive" or "negative." The value of exercise testing in prognostic risk stratification is considerably enhanced by recent reports of long-term follow-up data in asymptomatic and symptomatic patients. Powerful prognostic information can be obtained when the clinical, electrocardiographic and physiologic data from the exercise test are used to formulate the post-test risk of a cardiac event, even in patients whose coronary anatomy is known. The changing role of the exercise electrocardiogram as a diagnostic and prognostic test is reviewed, with emphasis on the strengths and limitations of the procedure.

Angina Pectoris↗

Prognostic value of the Duke treadmill score in the elderly.

OBJECTIVES: The purpose of this study was to test the hypothesis that the Duke treadmill score works less well for risk stratification in patients age 75 years or above. BACKGROUND: Although the Duke treadmill score is generally effective for risk stratification, its prognostic value in the elderly may be limited because they have a higher prevalence of coronary artery disease (CAD), more severe CAD and a lower exercise tolerance. METHODS: The study population consisted of 247 patients age 75 years or above, and the control population consisted of 2,304 patients below 75 years of age. All patients were symptomatic, had undergone exercise thallium testing between 1989 and 1991 and were followed for a median of >6.5 years. The Cox regression model was used to test the association of the Duke score (utilized both as a continuous variable and using previously published risk group cutoffs) with outcomes (cardiac death, nonfatal myocardial infarction [MI], late revascularization). RESULTS: Using the Duke score to risk-stratify the elderly, 26% were in the low risk group, 68% were in the intermediate risk group and 6% were in the high risk groups; seven-year cardiac survival was 86%, 85% and 69%, respectively (p = 0.45). There was also no significant association between these Duke score risk groups and all other outcome end points in the elderly. The Duke score as a continuous variable did not predict cardiac death (p = 0.43) or cardiac death or MI (p = 0.42), but did predict total cardiac events (which included late revascularization) (p = 0.0027). For the control population, more patients (55%) were in the low risk group, and the Duke score (as a continuous variable or in risk groups) was highly predictive of all end points (p = 0.0001). CONCLUSIONS: The Duke score predicted cardiac survival in younger patients but not in patients age 75 years or above. The majority of the elderly were classified as intermediate risk by the Duke score. Only a minority of the elderly were classified as low risk, but this group still had an annual cardiac mortality of 2%/year.

Age Factors↗

Melanoma in the elderly patient.

BACKGROUND: The incidence of cutaneous melanoma is rising steadily, and the rate of increase is among the highest for any form of cancer. Although the reliability of age as a prognostic factor is debatable, several studies suggest that age has an important prognostic use. HYPOTHESIS: Age alone does not predict a poor prognosis in the older patient with melanoma. SETTING: University teaching hospital. METHODS: A retrospective review was undertaken to identify patients aged 65 years or older with intermediate-thickness melanoma (1-4 mm). Two hundred thirteen such patients were identified. Data are given as mean +/- SD. RESULTS: The mean age was 72.2+/-6.1 years. The mean follow-up was 49 months. By univariate analysis, the mean disease-free survival (DFS) and overall survival (OS) for lymph node-positive patients was 36.0+/-9.6 and 56.0+/-10.6 months, respectively. The mean DFS for node-negative patients was 155.0+/-9.8 months, and the mean OS was 166.0+/-9.2 months (P<.001 for both). The mean DFS and OS for women were 151.0+/-11.2 and 163.0+/-10.9 months, respectively. In contrast, men had 116.0+/-9.5 months' DFS and 127.0+/-9.0 months' OS (P=.01 for both). By multivariate analysis, lymph node status was the most predictive variable for DFS and OS (P<.001 for both). Sex tended to affect OS (P=.02) but did not achieve prognostic significance on DFS (P=.09). Other factors such as location, ulceration, histological type, and mitoses per square millimeter failed to show any prognostic significance. Stratification into 3 age groups (65-70, 71-80, and >80 years) had no significant effect on DFS (P=.95) or OS (P=.92). CONCLUSIONS: Lymph node status is the most important prognostic factor in older patients with intermediate-thickness melanoma. Identification of high-risk factors may help stratify these patients for recommendation of more aggressive treatment or adjuvant therapies. Among these patients, age alone was not a significant prognostic factor in the clinical management of melanoma.

Age Factors↗

Allocation of patients to conditions in headache clinical trials: randomization, stratification, and treatment matching.

Assuming control over the allocation of patients to treatment conditions is a fundamental element of any comparative clinical trial. There are three critical considerations investigators must balance in choosing an allocation scheme: reducing bias in patient allocation, producing balanced patient groups across treatment arms, and reducing the likelihood of errors attributable to chance variation. The authors review the principles of three key approaches to the allocation of patients to conditions within clinical trials, and their respective advantages with regard to these critical considerations. These allocation methods include randomization, stratification, and patient-treatment matching. Randomization is fundamental to most clinical trials. Stratification is an advanced step in a systematic program of research investigating the efficacy and effectiveness of an intervention. If the trial has less than 100 per arm and there is a known prognostic factor, stratification is the best choice to ensure equal allocation across groups. Treatment matching (tailoring) attempts to match the most appropriate treatment to a specific patient based on a priori hypotheses. Two techniques used for exploring treatment matching are: patient typologies (patient profiling), and aptitude-treatment interactions. Additional details pertaining to the rationale for selecting among these various approaches to patient allocation is provided, and their methodology is summarized with specific consideration for their application within clinical trials of headache treatment.

Analysis of Variance↗

Advances in myeloma genetics and prospects for pharmacogenomic testing in multiple myeloma.

Pharmacogenomic studies in multiple myeloma, a neoplasia of clonally expanded malignant bone marrow plasma cells, are helping to set the stage for individualized therapy. Although relatively few in numbers, these studies are already providing new therapeutic targets and avenues for drug discoveries as well as contributing to novel prognostic markers in multiple myeloma. High-throughput mutation screening of the kinome promises to identify further novel targets for therapy. Genetics and gene expression profiling technology have improved molecular-based patient stratification and prognostic staging, expanded knowledge of the molecular mechanism of chemotherapeutic agents, and provided a better understanding of myeloma bone disease. The use of pharmacogenomic strategies in myeloma is thus already changing medical practice.

Humans↗

Development and internal validation of a six-gene prognostic model based on galactose metabolism for overall survival in lung adenocarcinoma.

BACKGROUND: Lung cancer remains a leading cause of cancer incidence and mortality globally. Metabolic reprogramming promotes tumor progression and shapes an immunosuppressive tumor microenvironment. Galactose metabolism is involved in multiple malignancies, but its prognostic value in lung adenocarcinoma (LUAD) remains unclear. This study aimed to develop and internally validate a galactose metabolism-related multigene prognostic model for LUAD. METHODS: A retrospective prognostic model development and internal validation study was performed using RNA sequencing (RNA-seq) and clinical data from 585 LUAD patients in The Cancer Genome Atlas (TCGA). Differential expression, functional enrichment, univariate and multivariate Cox regression were applied to construct a prognostic gene signature. Internal validation was performed using bootstrap resampling. Model performance was evaluated by time-dependent receiver operating characteristic (ROC), C-index, calibration, and Kaplan-Meier analysis. Associations between the model and immune infiltration, immunotherapy responsiveness, and tumor stemness were also analyzed. RESULTS: A six-gene prognostic model (GALT, GANC, PGM1, GALM, B4GALT1, PGM2) was developed. The model showed good discrimination with 1-, 3-, and 5-year area under the curve (AUC) values of 0.719, 0.693, and 0.684, respectively. The low-risk group exhibited significantly longer survival, increased antitumor immune infiltration (CD8+ T cells, M1 macrophages, activated CD4+ memory T cells), higher expression of T cell proliferation-related genes, lower immune checkpoint expression, better predicted immunotherapy response, and lower tumor stemness compared with the high-risk group. CONCLUSIONS: We developed and internally validated a six-gene prognostic model for LUAD based on galactose metabolism. The model shows moderate prognostic performance and is associated with antitumor immunity and tumor stemness. It may be used for prognostic risk stratification and to guide personalized immunotherapy in LUAD.

Galactose metabolism↗

Adjuvant chemotherapy with cyclophosphamide, doxorubicin, and cisplatin in patients with completely resected stage I non-small-cell lung cancer. The Lung Cancer Study Group.

BACKGROUND: Most studies of adjuvant chemotherapy, radiotherapy, or immunotherapy in non-small-cell lung cancer patients with complete surgical resection of disease have shown negative results. However, two studies of stage II and III disease by our Lung Cancer Study Group suggested an advantage to adjuvant therapy with cyclophosphamide, doxorubicin, and cisplatin (CAP). PURPOSE: Since neither of those studies had an untreated control, the Lung Cancer Study Group undertook a trial that included a control group and also offered the potential benefit of adjuvant therapy with CAP to patients with T1, N1 or T2, N0 (stage I) non-small-cell lung cancer. METHODS: After complete resection, eligible patients with stage I disease were classified by known prognostic factors and randomly assigned to receive or not to receive four courses of CAP at 3-week intervals beginning on day 30 after surgery. The CAP regimen consisted of 400 mg/m2 cyclophosphamide, 40 mg/m2 doxorubicin, and 60 mg/m2 cisplatin. Stratification by prognostic factors was as follows: histology (squamous versus nonsquamous), white blood cell count before surgery (> or = 9100/mm3 versus < 9100/mm3), and Karnofsky performance status before surgery (< or = 90% versus 100%). RESULTS: Of the 269 patients entered in the study, 101 had recurrence and 127 have died. Mean time since randomization is 6.4 years; mean follow-up is 3.8 years. There were no differences in time to recurrence or overall survival (not stratified by histology) between the two groups, even when analyses were adjusted for prognostic variables. There was one treatment-related death on the CAP arm due to infection during neutropenia. Only 53% of the eligible patients received all four courses of CAP, and only 57% of such patients received all four cycles on time. In 74% of the patients, the site of initial recurrence was distant. CONCLUSIONS: The most likely explanations for the lack of efficacy of CAP are poor compliance to the protocol and relative inactivity of the regimen, compared with the activity of drug combinations used in more recent studies. On the basis of this trial, adjuvant therapy with CAP should not be recommended for patients with resected stage I lung cancer. IMPLICATIONS: Further trials to test adjuvant therapy are indicated, but investigators should use better antiemetics to improve patient compliance as well as more active chemotherapy regimens.

Aged↗

The Role of Surgical Staging for Cervical Cancer.

Recent trends in gynecologic oncology have favored surgical staging of disease not only to define local extent, but more importantly nodal involvement. For cervical cancer, surgical staging includes intraperitoneal exploration, cytological washings, direct tumor palpation, and para-aortic with or without pelvic lymph node (LN) dissection. In the Gynecologic Oncology Group (GOG) experience, extraperitoneal selective para-aortic lymphadenectomy was associated with a lower risk of enteric complications following radiation for advanced cervical cancer and was, therefore, judged to be the preferred surgical procedure. In the GOG data base, para-aortic LN involvement was the most significant prognostic factor in multivariate analysis. If para-aortic LN were negative, pelvic LN metastases and tumor size were the most significant independent prognostic factors. Progression-free interval at 5 years decreased from 57% for patients with negative nodes to 34% and 12% for patients with pelvic or para-aortic LN metastases, respectively. As such, surgical staging must retain an integral role in protocol development to assure equal stratification of prognostic variables and, thereby, assess the benefit of innovative treatments for locally advanced cervical cancer in randomized prospective trials. The potential for lymphanglography and laparoscopy as alternatives to laparotomy are reviewed.

Journal Article↗

Prognostic value of the VE/VCO2 slope calculated from different time intervals in patients with suspected heart failure.

BACKGROUND: Maximal exercises testing, whether involving cycling- or walking-based protocols, are often not well tolerated in patients with chronic heart failure (CHF). The peak oxygen consumption and the slope of the relation between ventilation (V(E)) and carbon dioxide production (V(CO(2))) are independent predictors of outcome and help risk stratification. The prognostic usefulness of submaximal exercise testing is not clear. The aim of the present study was to assess the prognostic value of the V(E)/V(CO(2)) slope when derived from data acquired from submaximal exercise. METHODS: 394 patients referred with breathlessness and suspected heart failure (74% male) (mean+/-S.D.) age 60+/-12 years; BMI 27+/-5 performed a CPET to determine peak V(O(2)) and the V(E)/V(CO(2)) slope. The V(E)/V(CO(2)) slope was calculated using least squares regression from data acquired from the first 25% of exercise (mean V(E)/V(CO(2)) slope+/-SD; 30.6+/-5.7), 50% (29.6+/-6.9), below the ventilatory compensation point (sub-VCP) (29.9+/-6.8), and all data points (full slope) (32.1+/-7.8). For each measure, patients were divided into quartiles and Kaplan-Meier curves were constructed to determine probability of death after 24 months. The prognostic value of the different classifications was assessed using the chi(2) statistic from the Mantel-Cox log-rank test. RESULTS: During a mean follow-up period of 41+/-19 months, 48 patients died. For the V(E)/V(CO(2)) slope, the log-rank statistic was greatest for the full slope (chi(2)=53.7; P=0.0001), followed by the sub-VCP (chi(2)=45.5; P=0.0001), 50% (chi(2)=41.9; P=0.0001), and 25% (chi(2)= 26.0; P=0.01). The pair-wise log-rank statistic between the fourth and third quartiles was also greatest using the full slope (chi(2)=25.4; P=0.001) followed in order by the sub-VCP (chi(2)=20.1; P=0.001), 50% (chi(2)=19.7; P=0.001), and 25% (chi(2)=14.2; P=0.05). Using the stratified slope measurements entered into a Cox regression analysis using a forward LR stepwise elimination procedure; only the full slope remained significant (P=0.0001). CONCLUSIONS: The V(E)/V(CO(2)) slope should be calculated from all data points to optimise prognostic sensitivity. Data acquired from the first 50% of exercise and below the VCP provide adequate prognostic surrogates in patients who may not be able to perform maximal exercise testing (i.e. in patients with a respiratory exchange ratio<1.10).

Aged↗