Circulating tumor cells as trigger to hematogenous spreads and potential biomarkers to predict the prognosis in ovarian cancer.

Despite several improvements in the surgical field and in the systemic treatment, ovarian cancer (OC) is still characterized by high recurrence rates and consequently poor survival. In OC, there is still a great lack of knowledge with regard to cancer behavior and mechanisms of recurrence, progression, and drug resistance. The OC metastatization process mostly occurs via intracoelomatic spread. Recent evidences show that tumor cells generate a favorable microenvironment consisting in T regulatory cells, T infiltrating lymphocytes, and cytokines which are able to establish an "immuno-tolerance mileau" in which a tumor cell can become a resistant clone. When the disease responds to treatment, immunoediting processes and cancer progression have been stopped. A similar inhibition of the immunosuppressive microenvironment has been observed after optimal cytoreductive surgery as well. In this scenario, the early identification of circulating tumor cells could represent a precocious signal of loss of the immune balance that precedes cancer immunoediting and relapse. Supporting this hypothesis, circulating tumor cells have been demonstrated to be a prognostic factor in several solid tumors such as colorectal, pancreatic, gastric, breast, and genitourinary cancer. In OC, the role of circulating tumor cells is still to be defined. However, as opposed to healthy women, circulating tumor cells have been demonstrated in peripheral blood of OC patients, opening a new research field in OC diagnosis, treatment monitoring, and follow-up.

Analysis of prognostic factors for the development of metastases and survival in renal cell carcinoma patients

Introduction and objective. A number of prognostic factors have been reported for predicting survival in patients with renal cell carcinoma. Yet few studies have analyzed the effects of those factors at different stages of the disease process. In this study, different stages of disease progression starting from nephrectomy to metastasis, from metastasis to death, and from evaluation to death were evaluated. ^ Methods. In this retrospective follow-up study, records of 97 deceased renal cell carcinoma (RCC) patients were reviewed between September 2006 to October 2006. Patients with TNM Stage IV disease before nephrectomy or with cancer diagnoses other than RCC were excluded leaving 64 records for analysis. Patient TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were analyzed in relation to time to metastases. Time from nephrectomy to metastasis, TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were tested for significance in relation to time from metastases to death. Finally, analysis of laboratory values at time of evaluation, Eastern Cooperative Oncology Group performance status (ECOG), UCLA Integrated Staging System (UISS), time from nephrectomy to metastasis, TNM staging, Furhman Grade, age, tumor size, tumor volume, histology and patient gender were tested for significance in relation to time from evaluation to death. Linear regression and Cox Proportional Hazard (univariate and multivariate) was used for testing significance. Kaplan-Meier Log-Rank test was used to detect any significance between groups at various endpoints. ^ Results. Compared to negative lymph nodes at time of nephrectomy, a single positive lymph node had significantly shorter time to metastasis (p<0.0001). Compared to other histological types, clear cell histology had significant metastasis free survival (p=0.003). Clear cell histology compared to other types (p=0.0002 univariate, p=0.038 multivariate) and time to metastasis with log conversion (p=0.028) significantly affected time from metastasis to death. A greater than one year and greater than two year metastasis free interval, compared to patients that had metastasis before one and two years, had statistically significant survival benefit (p=0.004 and p=0.0318). Time from evaluation to death was affected by greater than one year metastasis free interval (p=0.0459), alcohol consumption (p=0.044), LDH (p=0.006), ECOG performance status (p<0.001), and hemoglobin level (p=0.0092). The UISS risk stratified the patient population in a statistically significant manner for survival (p=0.001). No other factors were found to be significant. ^ Conclusion. Clear cell histology is predictive for both time to metastasis and metastasis to death. Nodal status at time of nephrectomy may predict risk of metastasis. The time interval to metastasis significantly predicts time from metastasis to death and time from evaluation to death. ECOG performance status, and hemoglobin levels predicts survival outcome at evaluation. Finally, UISS appropriately stratifies risk in our population. ^

Gastric cancer survival amongst Hispanics- A Hispanic paradox? A case series study using the SEER 1973--2005 data registry

Stomach cancer is the fourth most common cancer in the world, and ranked 16th in the US in 2008. The age-adjusted rates among Hispanics were 2.8 times that of non-Hispanic Whites in 1998-2002. In spite of that, previous research has found that Hispanics with non-cardia adenocarcinoma of the stomach have a slightly better survival than non-Hispanic Whites. However, such previous research did not include a comparison with African-Americans, and it was limited to data released for the years 1973-2000 in the nine original Surveillance, Epidemiology, and End Results Cancer Registries. This finding was interpreted as related to the Hispanic Paradox, a phenomenon that refers to the fact that Hispanics in the USA tend to paradoxically have substantially better health than other ethnic groups in spite of what their aggregate socio-economic indicators would predict. We extended such research to the SEER 17 Registry, 1973-2005, with varying years of diagnosis per registry, and compared the survival of non-cardia adenocarcinoma of the stomach according to ethnicity (Hispanics, non-Hispanic Whites and African-Americans), while controlling for age, gender, marital status, stage of disease and treatment using Cox regression survival analysis. We found that Hispanic ethnicity by itself did not confer an advantage on survival from non-cardia adenocarcinoma of the stomach, but that being born abroad was independently associated with the apparent 'Hispanic Paradox' previously reported, and that such advantage was seen among foreign born persons across all race/ethnic groups.^

Estrogen-induced gene expression and patient survival in high-grade serous carcinoma of the ovary

Background. Assessment of estrogen receptor (ER) expression has inconsistent utility as a prognostic marker in epithelial ovarian carcinoma. In breast and endometrial cancers, the use of estrogen-induced gene panels, rather than ER expression alone, has shown improved prognostic capability. Specifically, over-expression of estrogen-induced genes in these tumors is associated with a better prognosis and signifies estrogen sensitivity that can be exploited with hormone antagonizing agents. It was therefore hypothesized that estrogen-induced gene expression in ovarian carcinoma would successfully predict outcomes and differentiate between tumors of varying estrogen sensitivities. Methods. Two hundred nineteen (219) patients with ovarian cancer who underwent surgery at M. D. Anderson between 2004 and 2007 were identified. Of these, eighty-three (83) patients were selected for inclusion because they had advanced stage, high-grade serous carcinoma of the ovary or peritoneum, had not received neoadjuvant chemotherapy, and had readily available frozen tissue for study. All patients had also received adjuvant treatment with platinum and taxane agents. The expression of seven genes known to be induced by estrogen in the female reproductive tract (EIG121, sFRP1, sFRP4, RALDH2, PR, IGF-1, and ER) was measured using qRT-PCR. Unsupervised cluster analyses of multiple gene permutations were used to categorize patients as high or low estrogen-induced gene expressors. QPCR gene expression results were then compared to ER and PR immunohistochemical (IHC) expression. Cox proportional hazards models were used to evaluate the effects of both individual genes and selected gene clusters on patient survival. Results. Median follow-up time was 38.7 months (range 1-68 months). In a multivariate model, overall survival was predicted by sFRP1 expression (HR 1.10 [1.02-1.19], p=0.01) and EIG121 expression (HR 1.28 [1.10-1.49], p<0.01). A cluster defined by EIG121 and ER was further examined because that combination appeared to reasonably segregate tumors into distinct groups of high and low estrogen-induced gene expressors. Shorter overall survival was associated with high estrogen-induced gene expressors (HR 2.84 [1.11-7.30], p=0.03), even after adjustment for race, age, body mass index, and residual disease at debulking. No difference in IHC ER or PR expression was noted between gene clusters. Conclusion. In sharp contrast to breast and endometrial cancers, high estrogen-induced gene expression predicts shorter overall survival in patients with high-grade serous ovarian carcinoma. An estrogen-induced gene biomarker panel may have utility as prognostic indicator and may be useful to guide management with estrogen antagonists in this population.^

Demographic analysis of Certified Industrial Hygienists (CIH) with the use of survival analysis techniques

Objective. The goal of this study is to characterize the current workforce of CIHs, the lengths of professional practice careers of the past and current CIHs.^ Methods. This is a secondary data analysis of data compiled from all of the nearly 50 annual roster listings of the American Board of Industrial Hygiene (ABIH) for Certified Industrial Hygienists active in each year since 1960. Survival analysis was performed as a technique to measure the primary outcome of interest. The technique which was involved in this study was the Kaplan-Meier method for estimating the survival function.^ Study subjects: The population to be studied is all Certified Industrial Hygienists (CIHs). A CIH is defined by the ABIH as an individual who has achieved the minimum requirements for education, working experience and through examination, has demonstrated a minimum level of knowledge and competency in the prevention of occupational illnesses. ^ Results. A Cox-proportional hazards model analysis was performed by different start-time cohorts of CIHs. In this model we chose cohort 1 as the reference cohort. The estimated relative risk of the event (defined as retirement, or absent from 5 consecutive years of listing) occurred for CIHs for cohorts 2,3,4,5 relative to cohort 1 is 0.385, 0.214, 0.234, 0.299 relatively. The result show that cohort 2 (CIHs issued from 1970-1980) has the lowest hazard ratio which indicates the lowest retirement rate.^ Conclusion. The manpower of CIHs (still actively practicing up to the end of 2009) increased tremendously starting in 1980 and grew into a plateau in recent decades. This indicates that the supply and demand of the profession may have reached equilibrium. More demographic information and variables are needed to actually predict the future number of CIHs needed. ^

Bayesian and survival model for tumor relapse status and disease-specific survival, with applications to breast cancer

Breast cancer is the most common non-skin cancer and the second leading cause of cancer-related death in women in the United States. Studies on ipsilateral breast tumor relapse (IBTR) status and disease-specific survival will help guide clinic treatment and predict patient prognosis.^ After breast conservation therapy, patients with breast cancer may experience breast tumor relapse. This relapse is classified into two distinct types: true local recurrence (TR) and new ipsilateral primary tumor (NP). However, the methods used to classify the relapse types are imperfect and are prone to misclassification. In addition, some observed survival data (e.g., time to relapse and time from relapse to death)are strongly correlated with relapse types. The first part of this dissertation presents a Bayesian approach to (1) modeling the potentially misclassified relapse status and the correlated survival information, (2) estimating the sensitivity and specificity of the diagnostic methods, and (3) quantify the covariate effects on event probabilities. A shared frailty was used to account for the within-subject correlation between survival times. The inference was conducted using a Bayesian framework via Markov Chain Monte Carlo simulation implemented in softwareWinBUGS. Simulation was used to validate the Bayesian method and assess its frequentist properties. The new model has two important innovations: (1) it utilizes the additional survival times correlated with the relapse status to improve the parameter estimation, and (2) it provides tools to address the correlation between the two diagnostic methods conditional to the true relapse types.^ Prediction of patients at highest risk for IBTR after local excision of ductal carcinoma in situ (DCIS) remains a clinical concern. The goals of the second part of this dissertation were to evaluate a published nomogram from Memorial Sloan-Kettering Cancer Center, to determine the risk of IBTR in patients with DCIS treated with local excision, and to determine whether there is a subset of patients at low risk of IBTR. Patients who had undergone local excision from 1990 through 2007 at MD Anderson Cancer Center with a final diagnosis of DCIS (n=794) were included in this part. Clinicopathologic factors and the performance of the Memorial Sloan-Kettering Cancer Center nomogram for prediction of IBTR were assessed for 734 patients with complete data. Nomogram for prediction of 5- and 10-year IBTR probabilities were found to demonstrate imperfect calibration and discrimination, with an area under the receiver operating characteristic curve of .63 and a concordance index of .63. In conclusion, predictive models for IBTR in DCIS patients treated with local excision are imperfect. Our current ability to accurately predict recurrence based on clinical parameters is limited.^ The American Joint Committee on Cancer (AJCC) staging of breast cancer is widely used to determine prognosis, yet survival within each AJCC stage shows wide variation and remains unpredictable. For the third part of this dissertation, biologic markers were hypothesized to be responsible for some of this variation, and the addition of biologic markers to current AJCC staging were examined for possibly provide improved prognostication. The initial cohort included patients treated with surgery as first intervention at MDACC from 1997 to 2006. Cox proportional hazards models were used to create prognostic scoring systems. AJCC pathologic staging parameters and biologic tumor markers were investigated to devise the scoring systems. Surveillance Epidemiology and End Results (SEER) data was used as the external cohort to validate the scoring systems. Binary indicators for pathologic stage (PS), estrogen receptor status (E), and tumor grade (G) were summed to create PS+EG scoring systems devised to predict 5-year patient outcomes. These scoring systems facilitated separation of the study population into more refined subgroups than the current AJCC staging system. The ability of the PS+EG score to stratify outcomes was confirmed in both internal and external validation cohorts. The current study proposes and validates a new staging system by incorporating tumor grade and ER status into current AJCC staging. We recommend that biologic markers be incorporating into revised versions of the AJCC staging system for patients receiving surgery as the first intervention.^ Chapter 1 focuses on developing a Bayesian method to solve misclassified relapse status and application to breast cancer data. Chapter 2 focuses on evaluation of a breast cancer nomogram for predicting risk of IBTR in patients with DCIS after local excision gives the statement of the problem in the clinical research. Chapter 3 focuses on validation of a novel staging system for disease-specific survival in patients with breast cancer treated with surgery as the first intervention. ^

Survival analysis of circulating tumor cells in triple-negative breast cancer

Background. Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females, accounting for 23% (1.38 million) of the total new cancer cases and 14% (458,400) of the total cancer deaths in 2008. [1] Triple-negative breast cancer (TNBC) is an aggressive phenotype comprising 10–20% of all breast cancers (BCs). [2-4] TNBCs show absence of estrogen, progesterone and HER2/neu receptors on the tumor cells. Because of the absence of these receptors, TNBCs are not candidates for targeted therapies. Circulating tumor cells (CTCs) are observed in blood of breast cancer patients even at early stages (Stage I & II) of the disease. Immunological and molecular analysis can be used to detect the presence of tumor cells in the blood (Circulating tumor cells; CTCs) of many breast cancer patients. These cells may explain relapses in early stage breast cancer patients even after adequate local control. CTC detection may be useful in identifying patients at risk for disease progression, and therapies targeting CTCs may improve outcome in patients harboring them. Methods . In this study we evaluated 80 patients with TNBC who are enrolled in a larger prospective study conducted at M D Anderson Cancer Center in order to determine whether the presence of circulating tumor cells is a significant prognostic factor in relapse free and overall survival . Patients with metastatic disease at the time of presentation were excluded from the study. CTCs were assessed using CellSearch System™ (Veridex, Raritan, NJ). CTCs were defined as nucleated cells lacking the presence of CD45 but expressing cytokeratins 8, 18 or 19. The distribution of patient and tumor characteristics was analyzed using chi square test and Fisher's exact test. Log rank test and Cox regression analysis was applied to establish the association of circulating tumor cells with relapse free and overall survival. Results. The median age of the study participants was 53years. The median duration of follow-up was 40 months. Eighty-eight percent (88%) of patients were newly diagnosed (without a previous history of breast cancer), and (60%) of patients were chemo naïve (had not received chemotherapy at the time of their blood draw for CTC analysis). Tumor characteristics such as stage (P=0.40), tumor size (P=69), sentinel nodal involvement (P=0.87), axillary lymph node involvement (P=0.13), adjuvant therapy (P=0.83), and high histological grade of tumor (P=0.26) did not predict the presence of CTCs. However, CTCs predicted worse relapse free survival (1 or more CTCs log rank P value = 0.04, at 2 or more CTCs P = 0.02 and at 3 or more CTCs P < 0.0001) and overall survival (at 1 or more CTCs log rank P value = 0.08, at 2 or more CTCs P = 0.01 and at 3 or more CTCs P = 0.0001. Conclusions. The number of circulating tumor cells predicted worse relapse free survival and overall survival in TNBC patients.^

The risk prediction for SPM and its impact on the survival in patients with head and neck squamous cell carcinoma

Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth common malignancy in the world, with high rates of developing second primary malignancy (SPM) and moderately low survival rates. This disease has become an enormous challenge in the cancer research and treatments. For HNSCC patients, a highly significant cause of post-treatment mortality and morbidity is the development of SPM. Hence, assessment of predicting the risk for the development of SPM would be very helpful for patients, clinicians and policy makers to estimate the survival of patients with HNSCC. In this study, we built a prognostic model to predict the risk of developing SPM in patients with newly diagnosed HNSCC. The dataset used in this research was obtained from The University of Texas MD Anderson Cancer Center. For the first aim, we used stepwise logistic regression to identify the prognostic factors for the development of SPM. Our final model contained cancer site and overall cancer stage as our risk factors for SPM. The Hosmer-Lemeshow test (p-value= 0.15>0.05) showed the final prognostic model fit the data well. The area under the ROC curve was 0.72 that suggested the discrimination ability of our model was acceptable. The internal validation confirmed the prognostic model was a good fit and the final prognostic model would not over optimistically predict the risk of SPM. This model needs external validation by using large data sample size before it can be generalized to predict SPM risk for other HNSCC patients. For the second aim, we utilized a multistate survival analysis approach to estimate the probability of death for HNSCC patients taking into consideration of the possibility of SPM. Patients without SPM were associated with longer survival. These findings suggest that the development of SPM could be a predictor of survival rates among the patients with HNSCC.^

Parenting and survival in anthropoid primates: Caretakers live longer

Most anthropoid primates are slow to develop, their offspring are mostly single births, and the interbirth intervals are long. To maintain a stable population, parents must live long enough to sustain the serial production of a sufficient number of young to replace themselves while allowing for the death of offspring before they can reproduce. However, in many species there is a large differential between the sexes in the care provided to offspring. Therefore, we hypothesize that in slowly developing species with single births, the sex that bears the greater burden in the care of offspring will tend to survive longer. Males are incapable of gestating infants and lactating, but in several species fathers carry their offspring for long periods. We predict that females tend to live longer than males in the species where the mother does most or all of the care of offspring, that there is no difference in survival between the sexes in species in which both parents participate about equally in infant care, and that in the species where the father does a greater amount of care than the mother, males tend to live longer. The hypothesis is supported by survival data for males and females in anthropoid primate species.

A subset of skin tumor modifier loci determines survival time of tumor-bearing mice

Studies of mouse models of human cancer have established the existence of multiple tumor modifiers that influence parameters of cancer susceptibility such as tumor multiplicity, tumor size, or the probability of malignant progression. We have carried out an analysis of skin tumor susceptibility in interspecific Mus musculus/Mus spretus hybrid mice and have identified another seven loci showing either significant (six loci) or suggestive (one locus) linkage to tumor susceptibility or resistance. A specific search was carried out for skin tumor modifier loci associated with time of survival after development of a malignant tumor. A combination of resistance alleles at three markers [D6Mit15 (Skts12), D7Mit12 (Skts2), and D17Mit7 (Skts10)], all of which are close to or the same as loci associated with carcinoma incidence and/or papilloma multiplicity, is significantly associated with increased survival of mice with carcinomas, whereas the reverse combination of susceptibility alleles is significantly linked to early mortality caused by rapid carcinoma growth (χ2 = 25.22; P = 5.1 × 10−8). These data indicate that host genetic factors may be used to predict carcinoma growth rate and/or survival of individual backcross mice exposed to the same carcinogenic stimulus and suggest that mouse models may provide an approach to the identification of genetic modifiers of cancer survival in humans.

Baseline serum cholestanol as predictor of recurrent coronary events in subgroup of Scandinavian simvastatin survival study

Objectives: To investigate whether baseline serum cholestanol:cholesterol ratio, which is negatively related to cholesterol synthesis, could predict reduction of coronary events in the Scandinavian simvastatin survival study.

Low IGF-I suppresses VEGF-survival signaling in retinal endothelial cells: Direct correlation with clinical retinopathy of prematurity

Retinopathy of prematurity is a blinding disease, initiated by lack of retinal vascular growth after premature birth. We show that lack of insulin-like growth factor I (IGF-I) in knockout mice prevents normal retinal vascular growth, despite the presence of vascular endothelial growth factor, important to vessel development. In vitro, low levels of IGF-I prevent vascular endothelial growth factor-induced activation of protein kinase B (Akt), a kinase critical for endothelial cell survival. Our results from studies in premature infants suggest that if the IGF-I level is sufficient after birth, normal vessel development occurs and retinopathy of prematurity does not develop. When IGF-I is persistently low, vessels cease to grow, maturing avascular retina becomes hypoxic and vascular endothelial growth factor accumulates in the vitreous. As IGF-I increases to a critical level, retinal neovascularization is triggered. These data indicate that serum IGF-I levels in premature infants can predict which infants will develop retinopathy of prematurity and further suggests that early restoration of IGF-I in premature infants to normal levels could prevent this disease.

A joint hazard and time scaling model to compare survival curves.

To provide a more general method for comparing survival experience, we propose a model that independently scales both hazard and time dimensions. To test the curve shape similarity of two time-dependent hazards, h1(t) and h2(t), we apply the proposed hazard relationship, h12(tKt)/ h1(t) = Kh, to h1. This relationship doubly scales h1 by the constant hazard and time scale factors, Kh and Kt, producing a transformed hazard, h12, with the same underlying curve shape as h1. We optimize the match of h12 to h2 by adjusting Kh and Kt. The corresponding survival relationship S12(tKt) = [S1(t)]KtKh transforms S1 into a new curve S12 of the same underlying shape that can be matched to the original S2. We apply this model to the curves for regional and local breast cancer contained in the National Cancer Institute's End Results Registry (1950-1973). Scaling the original regional curves, h1 and S1 with Kt = 1.769 and Kh = 0.263 produces transformed curves h12 and S12 that display congruence with the respective local curves, h2 and S2. This similarity of curve shapes suggests the application of the more complete curve shapes for regional disease as templates to predict the long-term survival pattern for local disease. By extension, this similarity raises the possibility of scaling early data for clinical trial curves according to templates of registry or previous trial curves, projecting long-term outcomes and reducing costs. The proposed model includes as special cases the widely used proportional hazards (Kt = 1) and accelerated life (KtKh = 1) models.

Validation of a new easy score to predict outcome in early stage renal cell carcinoma

Background e scopi dello studio. Il carcinoma renale rappresenta circa il 3% delle neoplasie e la sua incidenza è in aumento nel mondo. Il principale approccio terapeutico alla malattia in stadio precoce è rappresentato dalla chirurgia (nefrectomia parziale o radicale), sebbene circa il 30-40% dei pazienti vada incontro a recidiva di malattia dopo tale trattamento. La probabilità di recidivare può essere stimata per mezzo di alcuni noti modelli prognostici sviluppati integrando sia parametri clinici che anatomo-patologici. Il limite principale all’impiego nella pratica clinica di questi modelli è legata alla loro complessità di calcolo che li rende di difficile fruizione. Inoltre la stratificazione prognostica dei pazienti in questo ambito ha un ruolo rilevante nella pianificazione ed interpretazione dei risultati degli studi di terapia adiuvante dopo il trattamento chirurgico del carcinoma renale in stadio iniziale. Da un' analisi non pre-pianificata condotta nell’ambito di uno studio prospettico e randomizzato multicentrico italiano di recente pubblicazione, è stato sviluppato un nuovo modello predittivo e prognostico (“score”) che utilizza quattro semplici parametri: l’età del paziente, il grading istologico, lo stadio patologico del tumore (pT) e della componente linfonodale (pN). Lo scopo del presente studio era quello di validare esternamente tale score. Pazienti e Metodi. La validazione è stata condotta su due coorti retrospettive italiane (141 e 246 pazienti) e su una prospettica americana (1943 pazienti). Lo score testato prevedeva il confronto tra due gruppi di pazienti, uno a prognosi favorevole (pazienti con almeno due parametri positivi tra i seguenti: età < 60 anni, pT1-T3a, pN0, grading 1-2) e uno a prognosi sfavorevole (pazienti con meno di due fattori positivi). La statistica descrittiva è stata utilizzata per mostrare la distribuzione dei diversi parametri. Le analisi di sopravvivenza [recurrence free survival (RFS) e overall survival (OS)] sono state eseguite il metodo di Kaplan-Meier e le comparazioni tra i vari gruppi di pazienti sono state condotte utilizzando il Mantel-Haenszel log-rank test e il modello di regressione di Cox. Il metodo di Greenwood è stato utilizzato per stimare la varianza e la costruzione degli intervalli di confidenza al 95% (95% CI), la “C-statistic” è stata utilizzata per descrivere l’ accuratezza dello score. Risultati. I risultati della validazione dello score condotta sulle due casistiche retrospettive italiane, seppur non mostrando una differenza statisticamente significativa tra i due gruppi di pazienti (gruppo favorevole versus sfavorevole), sono stati ritenuti incoraggianti e meritevoli di ulteriore validazione sulla casistica prospettica americana. Lo score ha dimostrato di performare bene sia nel determinare la prognosi in termini di RFS [hazard ratio (HR) 1.85, 95% CI 1.57-2.17, p < 0.001] che di OS [HR 2.58, 95% CI 1.98-3.35, p < 0.001]. Inoltre in questa casistica lo score ha realizzato risultati sovrapponibili a quelli dello University of California Los Angeles Integrated Staging System. Conclusioni. Questo nuovo e semplice score ha dimostrato la sua validità in altre casistiche, sia retrospettive che prospettiche, in termini di impatto prognostico su RFS e OS. Ulteriori validazioni su casistiche internazionali sono in corso per confermare i risultati qui presentati e per testare l’eventuale ruolo predittivo di questo nuovo score.

Brachial blood pressure but not carotid arterial waveforms predict cardiovascular events in elderly female hypertensives

Central arterial waveforms and related indices of large artery properties can be determined with relative ease. This would make them an attractive adjunct in the risk stratification for cardiovascular disease. Although they have been associated with some classical risk factors and the presence of coronary disease, their prospective value in predicting cardiovascular outcomes is unknown. The present study determined the relative predictive value for cardiovascular disease-free survival of large artery properties as compared with noninvasive brachial blood pressure alone in a population of elderly female hypertensive subjects. We measured systemic arterial compliance, central systolic pressure, and carotid augmentation index in a subset of female participants in the Second Australian National Blood Pressure Study ( untreated blood pressure 169/88 +/- 12/ 8 mm Hg). There were a total of 53 defined events during a median of 4.1 years of follow-up in 484 women with complete measurements. Although baseline blood pressures at the brachial artery predicted cardiovascular disease-free survival ( hazard ratio [HR], 2.3; 95% CI, 1.3 to 4.1 for pulse pressure >= 81 versus < 81 mm Hg; P = 0.01), no such relation was found for carotid augmentation index ( HR, 0.80; 95% CI, 0.44 to 1.44; P value not significant) or systemic arterial compliance ( HR, 1.25; 95% CI, 0.72 to 2.16; P value not significant). Blood pressure, but not noninvasively measured central arterial waveforms, predict outcome in the older female hypertensive patient. Thus, blood pressure measurement alone is superior to measurement of arterial waveforms in predicting outcome in this group.