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PubMed2005

Radiotherapeutic techniques for prostate cancer, dose escalation and brachytherapy.

There is evidence to confirm a dose-response relationship in prostate cancer. The relative benefit is dependent on the clinical prognostic risk factors (T stage, Gleason score and presenting prostate-specific antigen [PSA]) being more favourable for intermediate-risk patients. Refinement of prognostic groups and clinical threshold parameters is ongoing. Escalation of dose in prostate radiotherapy using conventional techniques is limited by rectal tolerance. Substantial advances have been made in radiotherapy practice, such as the development of conformal radiotherapy (CFRT) and intensity-modulated radiotherapy (IMRT). Randomised data support the value of CFRT in reducing rectal toxicity. IMRT can permit higher-dose escalation while still respecting known rectal tolerance thresholds. Brachytherapy is a recognised alternative for low-risk prostate cancer subgroups. New radiotherapeutic strategies for prostate cancer include pelvic nodal irradiation, exploiting the presumed low alpha/beta ratio in prostate cancer for hypofractionation and combining external beam with high-dose-rate brachytherapy boosts. New image-guided methodologies will enhance the therapeutic ratio of any radiotherapy technique or dose escalation programme by enabling more reliable and accurate treatment delivery for improved patient outcomes.

Brachytherapy↗
PubMed1995

Ethnic differences in risk and prognostic factors for breast cancer.

BACKGROUND: Poor survival among African American patients with breast cancer has been attributed to low socioeconomic status and lack of access to health care. However, Hispanics of equivalent socioeconomic status and health care access exhibit much higher survival rates, almost comparable to whites. This suggests that biologic differences play a role in differences in breast cancer survival in addition to socioeconomic and health care access factors. METHODS: The authors studied clinical and molecular differences between patients with breast cancer of different ethnicity to determine biologic explanations for the observed differences in survival. Consecutive patients scheduled for breast biopsies were identified preoperatively and were interviewed. Blood was withdrawn for serum marker measurements, and tumor specimens collected at frozen section diagnosis were analyzed by flow cytometry, hormone receptor concentration, tumor grade, and Ki-67 nuclear antigen, HER-2/neu, and epidermal growth factor oncoprotein expression. RESULTS: Age, age at menarche, number of lymph nodes with metastasis, estrogen and progesterone receptor levels, ploidy status, S-phase, Ki-67, HER-2/neu expression, tumor grade, epidermal growth factor receptor expression, lipid-associated sialic acid (LASA), and carcinoembryonic antigen level were not significantly related to ethnicity. African Americans presented at a significantly more advanced stage and with significantly larger tumors. They were significantly heavier and had a significantly higher mean Quetelet's index and a significantly higher number of pregnancies and number of live births. Whites and Hispanics were significantly older at menopause. CONCLUSIONS: The molecular indices associated with breast cancer prognosis do not differ significantly among whites, African Americans, and Hispanics, suggesting that the reported differences in survival among these groups are not due to biologic differences in breast cancer among ethnic groups.

Black People↗
PubMed1986

Treatment of lymphoblastic lymphoma in adults.

Forty-four adult patients with lymphoblastic lymphoma (LBL) were treated according to one of two protocols. Both included (1) induction with cyclophosphamide, doxorubicin, vincristine, prednisone, and L-asparaginase; (2) CNS prophylaxis; and (3) maintenance therapy with methotrexate (MTX) and 6-mercaptopurine. In the second protocol, CNS prophylaxis began earlier than in the first protocol and included cranial irradiation and intrathecal (IT) MTX rather than simultaneous high-dose systemic and IT MTX. The overall response rate was 100% (95% complete). With a 26-month median follow-up, the 1-and 3-year actuarial freedom from relapse (FFR) for the composite patient group was 70% and 56%, respectively. The incidence of CNS relapse was reduced from 31% in the first protocol to 3% in the second protocol (P = .04, Gehan). Patients can be assigned retrospectively to low (n = 19) and high (n = 25) risk prognostic groups, as indicated by a multivariate analysis of pretreatment prognostic factors. High-risk is defined by Ann Arbor stage IV disease with bone marrow or CNS involvement or initial serum lactate dehydrogenase (LDH) concentration of greater than 300 IU/L (normal, less than 200). FFR of low- and high-risk groups at 5 years are 94% and 19%, respectively (P = .0006). Low-risk patients are highly curable using this approach to adult LBL. More intensive treatment for high-risk patients is warranted.

Adult↗
PubMed2002

[Comparative study of prognostic and risk factors for mortality in polymicrobial bacteremia-fungemia in a university hospital: development over 10 years].

OBJECTIVE: Eighty-two episodes of polymicrobial bacteremia in two time periods, 1986-87 and 1996-97, were compared to assess differences in risk factors and outcome to mortality. METHODS: A prospective, concurrent, anterograde study with univariate analysis of all episodes of polymicrobial bacteremia was performed in Hospital de la Princesa. Logistic regression analysis was applied to all significant variables (p < 0.05) in the univariate analysis in either of the two time periods. RESULTS: Variables showing statistically significant differences in incidence between the two time periods included the following: hospital acquired bacteremia; previous use of antibiotics; genitourinary, respiratory and cardiovascular manipulations; septic metastases; and absence of leukocytosis. These factors were more frequently present during 1986-87 than during 1996-97. The overall RR of outcome to mortality was five-fold greater during the first period than the second: RR 5.6 (CI 1.76-17.56) p < 0.001. The clinical characteristics at the onset of bacteremia associated with mortality in the first period were: underlying disease - < RR 2.20 (CI 1.18-4.08), steroid treatment - < RR 4.24 (CI 0.68-26.59), hypotension - < RR 2.05 (CI 1.0-4.17), and disseminated intravascular coagulation - < RR 2.31 (CI 1.69-3.35). Clinical characteristics at the onset of bacteremia associated with mortality in the second period were: hypotension - < RR 1.44 (CI 1.01-2.08), underlying disease - < RR 1.16 (CI 1.02-1.34), and disseminated intravascular coagulation - < RR 6.40 (CI 1.15-35.69). The variables independently associated with mortality in polymicrobial bacteremia were: period - < RR 2.05 (CI 1.50-2.10), underlying disease - < RR 7.05 (CI 2.68-7.50), hypotension - < RR 7.06 (CI 3.80-7.29), and (probably) vascular manipulations - < RR 3.41 (CI 0.85-4.53). CONCLUSION: Polymicrobial bacteremia-associated mortality was five-fold greater in 1986-87 than in 1996-97. The variables independently associated with mortality risk were underlying disease, hypotension, the period studied (which would include a number of variables not analyzed in this work) and, probably, vascular manipulations.

Adolescent↗
PubMed1991

[Prognostication of risk in surgical treatment of space-occupying formations of the liver].

From practice in the surgical management of 230 space-occupying formations of the liver (100 hepatic resections among other operations) a practical method for quantitative appraisal of the degree of the operative risk was elaborated. The method takes into account the relationship between the risk factors of various significance by multiplying the estimated probability of an unfavourable outcome in each of these factors, which is expressed as a risk multiplication coefficient determined for each of the 34 risk factors defined by the author. The factor of minimal and increased risk, unremovable and potentially removable, were determined. The suggested method allows the probability of an unfavourable outcome to be predicted on an individual basis and the therapeutic tactics to be reasonably changed in each specific case.

Adolescent↗
PubMed1997

International scoring system for evaluating prognosis in myelodysplastic syndromes.

Despite multiple disparate prognostic risk analysis systems for evaluating clinical outcome for patients with myelodysplastic syndrome (MDS), imprecision persists with such analyses. To attempt to improve on these systems, an International MDS Risk Analysis Workshop combined cytogenetic, morphological, and clinical data from seven large previously reported risk-based studies that had generated prognostic systems. A global analysis was performed on these patients, and critical prognostic variables were re-evaluated to generate a consensus prognostic system, particularly using a more refined bone marrow (BM) cytogenetic classification. Univariate analysis indicated that the major variables having an impact on disease outcome for evolution to acute myeloid leukemia were cytogenetic abnormalities, percentage of BM myeloblasts, and number of cytopenias; for survival, in addition to the above, variables also included age and gender. Cytogenetic subgroups of outcome were as follows: "good" outcomes were normal, -Y alone, del(5q) alone, del(20q) alone; "poor" outcomes were complex (ie, > or = 3 abnormalities) or chromosome 7 anomalies; and "intermediate" outcomes were other abnormalities. Multivariate analysis combined these cytogenetic subgroups with percentage of BM blasts and number of cytopenias to generate a prognostic model. Weighting these variables by their statistical power separated patients into distinctive subgroups of risk for 25% of patients to undergo evolution to acute myeloid leukemia, with: low (31% of patients), 9.4 years; intermediate-1 (INT-1; 39%), 3.3 years; INT-2 (22%), 1.1 years; and high (8%), 0.2 year. These features also separated patients into similar distinctive risk groups for median survival: low, 5.7 years; INT-1, 3.5 years; INT-2, 1.2 years; and high, 0.4 year. Stratification for age further improved analysis of survival. Compared with prior risk-based classifications, this International Prognostic Scoring System provides an improved method for evaluating prognosis in MDS. This classification system should prove useful for more precise design and analysis of therapeutic trials in this disease.

Acute Disease↗
PubMed1992

Nonconditional logistic regression analysis of risk factors in rheumatic heart disease.

The prognostic risk factors in 4323 patients with rheumatic heart disease, admitted from 1970 to 1990, were analysed. The overall mortality was 31.75% in this group of patients. Single factor analysis indicated that cardiac functional classification, time of death, month of death, cardiothoracic ratio, valvular lesions, cardiogenic shock, digitalis-induced arrhythmias, intercurrent pneumonia, pleurorrhea, and hypotension were related to the overall mortality and cardiac death. Multiple factor logistic analysis indicated that for the overall mortality, the independent prognostic factors included presence of cardiac functional classification, cardiothoracic ratio and cardiogenic shock; for cardiac death, the independent factors included cardiac functional classification, cardiothoracic ratio, cardiogenic shock, digitalis-induced arrhythmias and valvular lesions. The data analysis showed that these five factors were contributory to rheumatic heart disease with synergism.

Adolescent↗
PubMed2005

Angina with "normal" coronary arteries: a changing philosophy.

CONTEXT: Many women with angina are told that they have no significant heart disease following demonstration of normal or near-normal coronary arteries and are offered no specific treatment beyond reassurance. EVIDENCE ACQUISITION: MEDLINE and the Cochrane Database of Systematic Reviews were searched from their start dates until June 2004 for analysis using specific key words including diagnosis and therapy of angina with normal angiography and angina with normal coronary arteries. Reference lists of published articles and data of meeting presentations were also consulted. EVIDENCE SYNTHESIS: Normal or nonobstructive coronary disease at angiography is not uncommon and occurs in 10% of women presenting with ST-segment elevation myocardial infarction compared with 6% in men. Patients with evidence of myocardial ischemia or myocardial infarction and nonobstructive atherosclerotic disease of the coronary arteries are more likely to be women and nonwhite. Symptoms are often indistinguishable from those with obstructive coronary artery disease. The prognosis of patients with unstable angina and nonobstructive atherosclerotic coronary artery disease is not benign and includes a 2% risk of death or myocardial infarction at 30 days of follow-up. Recent work has shown that at least 20% of women with normal or nonobstructive angiography have myocardial ischemia, likely due to atherosclerosis-related endothelial dysfunction, which itself is associated with an increased risk of later adverse cardiac events and development of frank future obstructive disease. Randomized placebo-controlled studies have demonstrated that tricyclic antidepressants, beta-blockers, angiotensin-converting enzyme inhibitors, L-arginine, statins, and exercise may relieve symptoms, vascular dysfunction, or both; however, longer-term studies evaluating cardiac event rates need to be performed. CONCLUSIONS: Patients with chest pain and normal or nonobstructive coronary angiograms are predominantly women, and many have a prognosis that is not as benign as commonly thought. Assessment of endothelial function may help identify patients at risk for future cardiac events. Therapy should be directed at symptom relief with tricyclic agents and beta-blockers, and aggressive antiatherosclerotic therapy with statins, angiotensin-converting enzyme inhibitors, or both should be applied when risk factors are present or prognostic risk is high. Large-scale randomized trials need to be conducted to determine optimal ways of preventing clinical events.

Angina Pectoris↗
PubMed2026

Identification of a necroptosis-related lncRNA prognostic signature and the hub RBP HNRNPK in esophageal squamous cell carcinoma.

ObjectiveEsophageal squamous cell carcinoma (ESCC) is a malignant tumor with poor prognosis. Necroptosis is important for tumor immunity, but its role in ESCC remains unclear. This retrospective bioinformatics study aimed to investigate the prognostic value of necroptosis-related long non-coding RNAs (lncRNAs) and to identify key lncRNA-binding proteins (RBPs) in ESCC patients.MethodsRNA transcriptome and clinical data of ESCC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Necroptosis-related lncRNAs were identified through correlation analysis with necroptosis-related genes, subjected to consensus cluster analysis, and used to construct a prognostic risk model via least absolute shrinkage and selection operator (LASSO) regression. The hub RBP was experimentally validated by quantitative polymerase chain reaction (qPCR) using 30 pairs of ESCC and adjacent normal tissues from patients who underwent surgical resection.ResultsA total of 30 necroptosis-related lncRNAs were significantly correlated with overall survival (OS). The upregulated lncRNAs in the risk model were associated with high immune scores, innate immune cell infiltration, cluster 2 classification, and advanced T-stage disease (p&#x2009;<&#x2009;0.05). Three hub RBPs (HNRNPA1, HNRNPC, and HNRNPK) were identified through protein-protein interaction network analysis. qPCR confirmed that HNRNPK was significantly overexpressed in ESCC tissues compared to adjacent normal tissues (p&#x2009;<&#x2009;0.05).ConclusionsThe necroptosis-related lncRNA risk model is an independent prognostic factor for ESCC patients. HNRNPK was identified as a hub RBP significantly overexpressed in ESCC tissues. We hypothesize that HNRNPK may promote tumor progression through regulating proto-oncogene expression or modulating the immune microenvironment, though this requires further mechanistic validation.

Humans↗
PubMed2003

Reflections on the FIGO surgical staging of invasive epithelial ovarian cancer.

The main aims and requirements of any staging system are: to determine the anatomical extent of disease, to allow uniform reporting of treatment results, comparison of their efficacy and pooling of data from various institutions. It should be based on the mode of spread of the neoplasm, take into consideration prognostic risk factors and be of prognostic value. A critical review of the FIGO staging system for ovarian carcinoma indicates that these aims and requirements are not entirely fulfilled. Following are some examples. It does not include exact recommendations for comprehensive surgical staging in apparently early ovarian cancer and staging is therefore not performed uniformly. The presence of parenchymal liver and lung metastasis may be facilitated by modern imaging devices. However, according to FIGO rules only simple X-ray procedures are allowed preoperatively. The correlation between increasing stage and survival is inconsistent and sometimes contrary to that expected. Many known prognostic factors are not included in the present staging system. Although the aims of data pooling and of uniform reporting of treatment results have been achieved, the validity of some comparisons are questionable in view of the variations in staging. The intent of this review was not to belittle the major contribution of staging to research, understanding and management of ovarian carcinoma, but to highlight its deficiencies. New data have accumulated since the FIGO staging system of ovarian carcinoma has been adopted and should prompt consideration of modifications such as incorporation of modern diagnostic procedures and of some established prognostic markers and reshuffling of certain substages.

Biopsy, Needle↗
PubMed2005

[Reduction of cardiovascular risk in primary prophylaxy of coronary heart disease].

The purpose of the study was to evaluate the effects of Allicor, an Allium sativum (garlic) preparation with prolonged activity, on 10-year prognostic risk of coronary heart disease (CHD), acute myocardial infarction (MI) and sudden death in patients with elevated and high risk of CHD. 79 patients with elevated and high risk of CHD were included in a double blind randomized placebo-controlled study. They underwent multifactor evaluation of cardiovascular risk by algorithms based on the results of Framingham and Munster studies. Prolonged (12 months) administration of Allicor significantly reduced the multifactor risk, which was demonstrated by a 13.2% (p = 0.005) reduction of prognostic 10-year risk of CHD in men, and a 7.1% (p = 0.040) reduction of the same parameter in women. Prognostic 10-year risk of MI and sudden death in men was reduced by 26.1% (p = 0.025) and did not change significantly in women. In men the main factor of cardiovascular risk reduction was the decrease of cholesterol and low-density lipoprotein concentration by 23.5 +/- 6.6 mg/dl (p = 0.004), and in women - the increase of high-density lipoprotein level by 2.8 +/- 1.5 mg/dl (p = 0.040). The results of the study demonstrate that prolonged Allicor therapy can be applied to the large category of patients who are in need of atherosclerosis prevention.

Adult↗
PubMed1998

Value of exercise treadmill testing in women.

OBJECTIVES: We sought to determine the ability of a treadmill score to provide accurate diagnostic and prognostic risk estimates in women. BACKGROUND: Treadmill testing has been reported to have a lower accuracy for diagnosis of chest pain in women. The diagnostic and prognostic value of the Duke Treadmill Score (DTS) in women is unknown. METHODS: We determined the diagnostic and prognostic value of the DTS in 976 women and 2,249 men who underwent both treadmill testing and cardiac catheterization in a single institution from 1984 to 1994. RESULTS: Women and men differed significantly in DTS (1.6 vs. -0.3, p < 0.0001), disease prevalence (32% vs. 72% significant coronary artery disease [CAD], p < 0.001), and 2-year mortality (1.9% vs. 4.9%, p < 0.0001). The DTS provided information beyond clinical predictors of both coronary disease and survival in women and men. Although overall women had better survival, the DTS performed equally well in stratifying both genders into prognostic categories. The DTS actually performed better in women than in men for excluding disease, with fewer low risk women having any significant coronary disease (> or = 1 vessel with > or =75% stenosis) (20% vs. 47%, p < 0.001), or severe disease (3-vessel disease or > or =75% left main stenosis) (3.5% vs. 11.4%, p < 0.001). CONCLUSIONS: By combining several aspects of treadmill testing, the DTS effectively stratifies women into diagnostic and prognostic risk categories.

Coronary Disease↗
PubMed2003

Immediate treatment with bicalutamide 150mg as adjuvant therapy significantly reduces the risk of PSA progression in early prostate cancer.

OBJECTIVE: To evaluate the effect of bicalutamide ('Casodex') 150mg (in addition to standard care), on the risk of prostate-specific antigen (PSA) progression, in patients with early prostate cancer. METHODS: The bicalutamide 150mg Early Prostate Cancer (EPC) programme is the largest clinical trial programme in the treatment of prostate cancer to date. This paper reports the PSA progression data from the EPC programme at a median of 3years' follow-up, for the overall study population, and across the radical prostatectomy and radiotherapy primary therapy strategies. PSA progression was predefined as the earliest occurrence of PSA doubling from baseline, objective progression, or death from any cause. RESULT: Overall, bicalutamide 150 mg in addition to standard care significantly reduced the risk of PSA progression by 59% compared with standard care alone (HR 0.41; 95% CI 0.38, 0.45; p<<0.0001). Significant reductions were observed following radical prostatectomy (51%; HR 0.49; 95% CI 0.43, 0.56; p<<0.0001) and radiotherapy (58%; HR 0.42; 95% CI 0.33, 0.53; p<<0.0001). Further exploration of the data by disease stage, nodal status, Gleason score and pre-treatment PSA level revealed significant reductions in the risk of PSA progression across most prognostic risk factor subgroups. CONCLUSIONS: Bicalutamide 150mg significantly reduces the risk of PSA progression, irrespective of whether patients received radical prostatectomy or radiotherapy as standard care. The EPC programme is ongoing and further progression and survival data are awaited.

Adult↗
PubMed2026

Integrative analysis of the roles and prognostic value of RNA-binding proteins in papillary renal cell carcinoma.

RNA-binding proteins (RBPs) serve essential roles in various cancer types, but their functions in papillary renal cell carcinoma (pRCC) have not been elucidated to date. In our work, differentially expressed RBPs in pRCC were identified after acquisition of RNA-sequencing and clinical data related to pRCC from The Cancer Genome Atlas database(TCGA). Functional enrichment analysis and protein interaction network analysis, along with univariate and multivariate Cox regression analyses, were performed to uncover potential biological effects of the identified RBPs and screen the hub RBPs for pRCC prognosis. We identified 251 up-regulated and 129 down-regulated RBPs, and filtered out seven hub RBPs, namely, SRSF8, CD3EAP, HBS1L, ELAC2, MRPL34, NOP2 and IGF2BP2, for their prognostic relevance. A prognostic risk score model for overall survival of pRCC patients was constructed based on the seven hub RBPs. Further analysis showed that the low-risk group had higher survival rate than the high-risk group in both training and validation cohorts. The predictive accuracy was verified in the Human Protein Atlas database.In addition, we introduced the GSE15641 dataset from the Gene Expression Omnibus (GEO) database for independent external validation, and confirmed the expression levels of HBS1L, MRPL34 and IGF2BP2 through real-time quantitative PCR (RT-qPCR) and Western blotting (WB) using human renal tubular epithelial cell line HK-2 and human papillary renal cell carcinoma cell line Caki-2. In pRCC, CD3EAP was significantly elevated, while ELAC2, IGF2BP2, MRPL34, SRSF8 and HBS1L were significantly reduced. There was no significant difference between tumor and normal tissues in NOP2 expression. Risk score and tumor grade were independent prognostic factors associated with overall survival. In addition, we established a nomogram based on the seven prognostic RBPs to help predict overall survival at 1-3 years. In conclusion, seven differentially expressed hub RBPs were identified as potential prognostic biomarkers for pRCC. Our prognostic model might serve as a support for better treatment decision-making. Our work could provide potential new ideas for diagnosis and research on targeted drugs for pRCC.

Bioinformatics↗
PubMed1999

Hepatic resection for metastatic colorectal adenocarcinoma: a proposal of a prognostic scoring system.

BACKGROUND: Hepatic resection for metastatic colorectal cancer provides excellent longterm results in a substantial proportion of patients. Although various prognostic risk factors have been identified, there has been no dependable staging or prognostic scoring system for metastatic hepatic tumors. STUDY DESIGN: Various clinical and pathologic risk factors were examined in 305 consecutive patients who underwent primary hepatic resections for metastatic colorectal cancer. Survival rates were estimated by the Cox proportional hazards model using the equation: S(t) = [So(t)]exp(R-Ro), where So(t) is the survival rate of patients with none of the identified risk factors and Ro = 0. RESULTS: Preliminary multivariate analysis revealed that independently significant negative prognosticators were: (1) positive surgical margins, (2) extrahepatic tumor involvement including the lymph node(s), (3) tumor number of three or more, (4) bilobar tumors, and (5) time from treatment of the primary tumor to hepatic recurrence of 30 months or less. Because the survival rates of the 62 patients with positive margins or extrahepatic tumor were uniformly very poor, multivariate analysis was repeated in the remaining 243 patients who did not have these lethal risk factors. The reanalysis revealed that independently significant poor prognosticators were: (1) tumor number of three or more, (2) tumor size greater than 8 cm, (3) time to hepatic recurrence of 30 months or less, and (4) bilobar tumors. Risk scores (R) for tumor recurrence of the culled cohort (n = 243) were calculated by summation of coefficients from the multivariate analysis and were divided into five groups: grade 1, no risk factors (R = 0); grade 2, one risk factor (R = 0.3 to 0.7); grade 3, two risk factors (R = 0.7 to 1.1); grade 4, three risk factors (R= 1.2 to 1.6); and grade 5, four risk factors (R > 1.6). Grade 6 consisted of the 62 culled patients with positive margins or extrahepatic tumor. Kaplan-Meier and Cox proportional hazards estimated 5-year survival rates of grade 1 to 6 patients were 48.3% and 48.3%, 36.6% and 33.7%, 19.9% and 17.9%, 11.9% and 6.4%, 0% and 1.1%, and 0% and 0%, respectively (p < 0.0001). CONCLUSIONS: The proposed risk-score grading predicted the survival differences extremely well. Estimated survival as determined by the Cox proportional hazards model was similar to that determined by the Kaplan-Meier method. Verification and further improvements of the proposed system are awaited by other centers or international collaborative studies.

Adenocarcinoma↗