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PubMed2002

Predictors of progression of HRCT diagnosed fibrosing alveolitis in patients with rheumatoid arthritis.

BACKGROUND: Fibrosing alveolitis (FA) is the most serious pleuropulmonary extra-articular feature of rheumatoid arthritis (RA). Features that predict progression of FA in patients with RA have not yet been determined. OBJECTIVE: To identify clinical features that predict progressive FA in patients with RA. METHODS: An unselected cohort of 29 patients with RA and FA confirmed by high resolution computed tomography (HRCT) were studied prospectively for 24 months. Three monthly clinical assessment, four monthly pulmonary function tests, and yearly HRCT scanning was undertaken on these patients. Progressive FA was defined as >15% fall in carbon monoxide transfer factor (TLCO) with evidence of increasing FA on HRCT or death as a result of FA. RESULTS: During 24 months of follow up 10/29 (34%) patients had progressive FA. Progression on HRCT was seen as acute ground glass exacerbations or increasing reticular pattern lung involvement. Progressive FA was associated with the presence of bibasal crackles (p=0.041), TLCO (p=0.001), and extent (p=0.026) and distribution (p=0.031) of lung involvement on HRCT at initial presentation. When multiple logistic regression was used, only TLCO remained significant. Receiver operator curve analysis was employed to identify presenting TLCO of progressive FA. A TLCO <54% of the predicted value demonstrated 80% sensitivity and 93% specificity in predicting progressive FA. CONCLUSIONS: A TLCO <54% of the predicted value is a highly specific predictor of disease progression.

Aged↗
PubMed2005

The relation between intraocular pressure peak in the water drinking test and visual field progression in glaucoma.

AIM: To compare the results of the water drinking test between glaucomatous eyes with and without visual field progression. METHODS: Retrospective analysis of 76 eyes of 76 open angle glaucoma patients followed for a mean period of 26.0 (SD 13.8) months. Patients were submitted to the water drinking test at the beginning of the follow up period. Reliable achromatic automated perimetry tests performed during the studied period were used to characterise visual field progression. All subjects were under clinical therapy and had an intraocular pressure (IOP) lower than 17 mm Hg monitored by isolated measurements during the follow up period. The results of the water drinking test were compared between glaucomatous eyes with and without visual field progression. RESULTS: Twenty eight eyes reached definite visual field progression. There were no significant differences in the mean age, sex, race, basal IOP, number of antiglaucomatous drugs, initial mean deviation (MD), and corrected pattern standard deviation (CPSD) between eyes that showed visual field progression and the ones who did not progress. A significant difference of 1.9 (SD 0.6) mm Hg (p = 0.001, analysis of covariance; 95% CI 0.8 to 3.0) was observed between glaucomatous eyes that showed visual field deterioration and glaucomatous eyes that did not progress. A significant difference of 16.8% (SD 4.6%) in the mean percentage of IOP variation was also observed between the two groups (p<0.001, analysis of covariance; 95% CI 7.7 to 26.0). CONCLUSIONS: Mean IOP peak and percentage of IOP variation during water drinking test were significantly higher in patients with visual field progression compared with patients who did not progress.

Adult↗
PubMed1995

Serum lipoprotein(a) concentrations are related to coronary disease progression without new myocardial infarction.

OBJECTIVE: To examine the association between serum lipoprotein(a) and angiographically assessed coronary artery disease progression without new myocardial infarction. PATIENTS AND DESIGN: 85 patients with coronary artery disease who underwent serial angiography with an interval of at least two years were studied. Progression of coronary artery disease was defined as an increase in diameter stenosis of 15% or more. Vessels on which angioplasty had been performed were excluded from the analysis. The patients were classified into two groups: a progression group without new myocardial infarction (n = 48) and non-progression group (n = 37). Risk factors including lipoprotein(a) were evaluated to see how they were related to progression without myocardial infarction. RESULTS: There were no differences between the two groups in the following factors: age, gender, the time interval between the angiographic studies, the distribution of the analysed coronary arteries, and history of well established coronary risk factors. Univariate analysis showed that serum lipoprotein(a) (P = 0.0002), cigarette smoking between the studies (P = 0.002), serum high density lipoprotein (P = 0.003), and serum low density lipoprotein (P = 0.01) were related to progression without myocardial infarction. Multivariate analysis selected two independent factors for progression without myocardial infarction: serum lipoprotein(a) (P = 0.003) and serum high density lipoprotein (P = 0.03). CONCLUSIONS: Serum lipoprotein(a) concentrations are closely related to the progression of coronary artery disease without new myocardial infarction. Lipoprotein(a) lowering treatment may be needed to prevent disease progression in patients with coronary artery disease and high serum lipoprotein(a).

Aged↗
PubMed2005

A combination of genetic polymorphisms increases the risk of progressive disease in chronic hepatitis C.

BACKGROUND: There is increasing interest in the influence of host genetic factors on hepatic fibrosis, and whether genetic markers can reliably identify subjects at risk of developing severe disease. We hypothesised that hepatitis C virus (HCV) infected subjects with progressive fibrosis, classified using strict criteria based on histology at biopsy in addition to disease duration would be more likely to inherit several genetic polymorphisms associated with disease progression compared with subjects with a low rate of disease progression. METHODS: We examined polymorphisms in eight genes that have been reported to have an association with hepatic fibrosis. RESULTS: Associations between polymorphisms in six genes and more rapidly progressing fibrosis were observed, with individual adjusted odds ratios ranging from 2.1 to 4.5. The relationship between rapidly progressing fibrosis and possession of > or =3, > or =4, or > or =5 progression associated alleles was determined and the adjusted odds ratios increased with increasing number of progression associated alleles (9.1, 15.5, and 24.1, respectively). Using logistic regression analysis, a predictive equation was developed and tested using a second cohort of patients with rapidly progressing fibrosis. The predictive equation correctly classified 80% of patients in this second cohort. CONCLUSIONS: This approach may allow determination of a genetic profile predictive of rapid disease progression in HCV and identify patients warranting more aggressive therapeutic management.

Adult↗
PubMed2003

Expression of beta2 adrenoreceptors on peripheral blood mononuclear cells in patients with primary and secondary progressive multiple sclerosis: a longitudinal six month study.

BACKGROUND: Beta(2) adrenoreceptor expression on peripheral blood mononuclear cells is increased in progressive multiple sclerosis. This increase has been correlated with disease activity in relapsing-remitting multiple sclerosis. OBJECTIVE: To determine the beta(2) adrenoreceptor expression in primary and secondary progressive multiple sclerosis in relation to findings on magnetic resonance imaging (MRI) and clinical disease activity. METHODS: 10 patients with multiple sclerosis were studied (five with primary progressive and five with secondary progressive forms of the disease) over a period of six months. Monthly clinical and MRI assessments of the brain and spinal cord were carried out. Beta(2) adrenoreceptor expression was assessed monthly using a ligand binding assay with [(125)I]iodocyanopindolol. Expression of beta(2) adrenoceptors on peripheral blood mononuclear cells was also assessed in five normal controls over a similar period. RESULTS: The mean (SEM) value of beta(2) adrenoreceptor density for the five normal controls was 1346 (183) sites/cell, with affinity Kd of 120 (40) pM. MRI disease activity in primary progressive multiple sclerosis was reported on two occasions and on those occasions the expression of beta(2) adrenoreceptors was increased in excess of 1900 sites/cell; in the remaining 28 observations beta(2) adrenoreceptor expression was within the normal range (800 to 1900 sites/cell). In patients with secondary progressive disease, MRI disease activity was observed on 16 occasions. In these patients expression of beta(2) adrenoreceptors was increased in excess of 2000 sites/cell in all measurements except in one subject who did not show MRI activity throughout the six months period of study. The affinity of the receptors was within the normal range in all cases. CONCLUSIONS: Increased expression of beta(2) adrenoreceptors was correlated with MRI disease activity in two patients with primary progressive multiple sclerosis. In secondary progressive multiple sclerosis, increased expression of beta(2) adrenoreceptors tended not to correlate with MRI disease activity. This may reflect a persistent Th1 immune reaction in the secondary progressive form of the disease.

Adult↗
PubMed2005

Socioeconomic differences in progression of carotid intima-media thickness in the Atherosclerosis Risk in Communities study.

OBJECTIVE: To examine the association of socioeconomic factors with progression of carotid intimal-medial thickness (IMT) in middle-aged adults. Cross-sectional associations of IMT with socioeconomic status (SES) have been demonstrated in middle-aged cohorts. It is unclear whether these factors are associated with progression of IMT. METHODS AND RESULTS: We examined IMT progression over 9 years among a middle-aged cohort of 12,085 black and white subjects free of cardiovascular disease recruited from 4 US sites participating in the Atherosclerosis Risk in Communities (ARIC) study. Baseline IMT was inversely related to SES among whites and blacks. Repeated measures regression models of IMT progression showed moderate inverse relationships of IMT progression with income in whites so that the difference in 5-year IMT progression rates between the highest and lowest categories was -11.5 microm (CI, -17.4 to -5.6). In contrast, among blacks, this gradient is reversed, with an 11.1 microm (CI, -0.1 to 22.3) difference in 5-year progression between highest and lowest income category. Generally, similar patterns were observed for other socioeconomic indicators. Patterns were not accounted for by baseline cardiovascular risk factors. CONCLUSIONS: SES is inversely related to IMT progression in middle-aged whites but positively related to IMT progression among middle-aged blacks. These differences do not appear to be attributable to selective attrition or higher IMT among blacks at baseline.

Black People↗
PubMed1996

Lipoprotein subclasses in the Monitored Atherosclerosis Regression Study (MARS). Treatment effects and relation to coronary angiographic progression.

Accumulating evidence suggests that triglyceride-rich lipoproteins contribute to coronary artery disease. Using data from the Monitored Atherosclerosis Regression Study, an angiographic trial of middle-aged men and women randomized to lovastatin or placebo, we investigated relationships between lipoprotein subclasses and progression of coronary artery atherosclerosis. Coronary artery lesion progression was determined by quantitative coronary angiography in low-grade ( < 50% diameter stenosis), high-grade ( > or = 50% diameter stenosis), and all coronary artery lesions in 220 baseline/2-year angiogram pairs. Analytical ultracentrifugation was used to measure lipoprotein masses that were statistically evaluated for treatment group differences and relationships to progression of coronary artery atherosclerosis. All low density lipoprotein (LDL), intermediate density lipoprotein (IDL), and very low density lipoprotein (VLDL) masses were significantly lowered and all high density lipoprotein (HDL) masses were significantly raised with lovastatin therapy. The mass of smallest LDL (Svedberg flotation rate [Sf] 0 to 3), IDL (Sf 12 to 20), all VLDL subclasses (Sf 20 to 60, Sf 60 to 100, and Sf 100 to 400), and peak LDL flotation rate were significantly related to the progression of coronary artery lesions, specifically low-grade lesions. Greater baseline levels of HDL3, were related to a lower likelihood of coronary artery lesion progression. In multivariate analyses, small VLDL (Sf 20 to 60) and HDL3 mass were the most important correlates of coronary artery lesion progression. These results provide further evidence for the importance of triglyceride-rich lipoproteins in the progression of coronary artery disease. In addition, these results present new evidence for the possible protective role of HDL3 in the progression of coronary artery lesions. More specific information on coronary artery lesion progression may be obtained through the study of specific apolipoprotein B-containing lipoproteins.

Adult↗
PubMed2002

Risk factors for progression of aortic atheroma in stroke and transient ischemic attack patients.

BACKGROUND AND PURPOSE: Aortic atheroma is an independent risk factor for stroke and undergoes temporal progression. Clinical and risk factor associations of such progression are unknown. Hyperhomocysteinemia has been linked with atherosclerosis, including that in the cerebral vasculature. This study investigated associations between elevated homocysteine levels and other stroke vascular risk factors and the risk of aortic atheroma progression in patients with cerebrovascular disease. METHODS: Fifty-seven stroke and 21 transient ischemic attack patients underwent multiplanar transesophageal echocardiograms within 1 month of symptom onset and again at 9 months. Aortic atheroma was graded and stratified by use of existing criteria. Stroke risk factors; use of anticoagulant, antiplatelet, and hypolipidemic drugs; and clinical and etiological subtypes of stroke were recorded and compared in patients stratified for the presence or absence of aortic atheroma progression. RESULTS: Of the 78, 29 (37%) progressed, 32 (41%) remained unchanged, and 17 (22%) regressed. Progression was most marked at the aortic arch (P=0.005), followed by the ascending segment (P<0.04). In nearly two thirds of the patients in whom aortic atheroma remained unchanged over 9 months, no atheroma was evident on baseline transesophageal echocardiogram. Only homocysteine levels > or =14.0 micromol/L (P=0.02), total anterior cerebral infarct (P=0.02), and large-artery atherosclerosis (P=0.005) significantly correlated with progression. CONCLUSIONS: Among vascular risk factors, elevated homocysteine levels are associated with aortic atheroma progression. Stroke and transient ischemic attack patients with aortic atheroma should undergo assessment of homocysteine levels, which, if elevated, may be treated with vitamins in an effort to arrest aortic atheroma progression.

Anticoagulants↗
PubMed2006

Risk factors for progression of peripheral arterial disease in large and small vessels.

BACKGROUND: Data on the natural history of peripheral arterial disease (PAD) are scarce and are focused primarily on clinical symptoms. Using noninvasive tests, we assessed the role of traditional and novel risk factors on PAD progression. We hypothesized that the risk factors for large-vessel PAD (LV-PAD) progression might differ from small-vessel PAD (SV-PAD). METHODS AND RESULTS: Between 1990 and 1994, patients seen during the prior 10 years in our vascular laboratories were invited for a new vascular examination. The first assessment provided baseline data, with follow-up data obtained at this study. The highest decile of decline was considered major progression, which was a -0.30 ankle brachial index decrease for LV-PAD and a -0.27 toe brachial index decrease for SV-PAD progression. In addition to traditional risk factors, the roles of high-sensitivity C-reactive protein, serum amyloid-A, lipoprotein(a), and homocysteine were assessed. Over the average follow-up interval of 4.6+/-2.5 years, the 403 patients showed a significant ankle brachial index and toe brachial index deterioration. In multivariable analysis, current smoking, ratio of total to HDL cholesterol, lipoprotein(a), and high-sensitivity C-reactive protein were related to LV-PAD progression, whereas only diabetes was associated with SV-PAD progression. CONCLUSIONS: Risk factors contribute differentially to the progression of LV-PAD and SV-PAD. Cigarette smoking, lipids, and inflammation contribute to LV-PAD progression, whereas diabetes was the only significant predictor of SV-PAD progression.

Aged↗
PubMed2001

Progression and clinical recurrence of symptomatic middle cerebral artery stenosis: a long-term follow-up transcranial Doppler ultrasound study.

BACKGROUND AND PURPOSE: Patients with symptomatic intracranial atherosclerotic stenosis have a high rate of recurrence. We conducted a prospective study to determine which factors are associated with the progression of symptomatic middle cerebral artery (MCA) stenosis and to evaluate the relationship between progression and clinical recurrence. METHODS: Between January 1996 and February 2000, of a total of 2564 consecutive first-ever transient ischemic attack (TIA) or stroke patients admitted to our cerebrovascular unit, 145 showed an MCA stenosis signal on transcranial Doppler (TCD) on admission, and 40 fulfilled all criteria to enter this study, including angiographic confirmation. Patients were prescribed antiplatelet or anticoagulant agents following the criteria of the neurologist in charge. TCD recordings and clinical interviews were performed regularly during follow-up. Progression of MCA stenosis was defined as an increase >30 cm/s in TCD-recorded maximum mean flow velocity. Logistic regression analyses were used to identify predictors of progression and clinical recurrence. RESULTS: With a median follow-up of 26.55 months, 13 (32.5%) MCA stenoses progressed, 3 (7.5%) regressed, and 24 (60%) remained stable. Absence of significant extracranial internal carotid artery (ICA) stenosis (P=0.049) and the use of oral anticoagulants (P=0.045) were significantly associated with a lower progression rate in univariate analysis, and anticoagulation remained an independent predictor when a logistic regression model was applied (OR 7.25, CI 1.1 to 48.1, P=0.019). A new ischemic event during follow-up in the territory supplied by the stenosed MCA occurred in 8 cases (20%), and 13 patients had a major vascular event. Progression of the MCA stenosis detected by TCD was independently associated with a new ipsilateral ischemic event (OR 2.89, CI 1.09 to 7.71, P=0.031) and with the occurrence of any major vascular event (OR 7.03, CI 1.6 to 30.9, P=0.0071). CONCLUSIONS: Progression of symptomatic MCA stenosis detected by means of TCD predicts clinical recurrence. Anticoagulation is independently associated with a lower progression rate of symptomatic MCA stenosis.

Administration, Oral↗
PubMed2005

Progression of airway dysplasia and C-reactive protein in smokers at high risk of lung cancer.

RATIONALE: Chronic inflammation has been implicated in the development of airway dysplasia and lung cancer. It is unclear whether circulating biomarkers of inflammation could be used to predict progression of airway dysplasia. OBJECTIVE: We determined whether circulating levels of C-reactive protein (CRP) or other inflammatory biomarkers could predict progression of bronchial dysplasia in smokers over 6 mo. METHODS: The plasma levels of CRP, interleukins 6 and 8, and monocyte chemoattractant protein 1 were measured at baseline in 65 ex- and current smokers who had at least one site of bronchial dysplasia > 1.2 mm in size. Additional bronchial biopsies were taken after 6 mo from the same sites where dysplastic lesions were discovered at baseline. Progressive dysplastic lesions were defined as worsening of the dysplastic lesion by at least two grades or development of new dysplastic lesions. RESULTS: Half of the participants developed progressive dysplastic lesions after 6 mo. The baseline CRP levels in these participants were 64% higher than those without progressive disease (p = 0.027). Only one of eight (13%) participants with CRP < or = 0.5 mg/L developed progressive disease, whereas 31 of 57 (54%) participants with CRP > 0.5 mg/L developed progressive disease (p = 0.011). The odds of developing progressive disease were 9.6-fold higher in the latter than in the former group. CONCLUSION: Plasma CRP, in concert with lung function and pack-years of smoking, appears to have excellent predictive powers in identifying participants with bronchial dyplastic lesions whose lesions progress to more advanced stages of dysplasia.

Biomarkers↗
PubMed2003

Comparison of different methods for detecting glaucomatous visual field progression.

PURPOSE: To compare the performance characteristics of seven methods for analyzing glaucomatous visual field progression, using a combination of real patient data and computer simulation techniques. METHODS: The initial and final visual field results, separated by 7 years and measured with the full-threshold 30-2 program of the Humphrey Field Analyzer (Carl Zeiss Meditec, Dublin, CA) of 76 patients with open-angle glaucoma were used. A computer simulation program generated 14 interim semiannual visual fields under conditions of high, moderate, and no variability. Progression was analyzed using the methods of the Advanced Glaucoma Intervention Study (AGIS), the Collaborative Initial Glaucoma Treatment Study (CIGTS), three criteria based on the Glaucoma Change Probability (GCP) analysis, and two criteria based on point-wise linear regression analysis (PLRA). Specificities were calculated by using the same visual field of each patient as both the initial and final field (no progression) under conditions of moderate and high variability. RESULTS: Under the no-variability condition, progression rates were 18% for the AGIS, 36% for CIGTS, 47% to 62% for the three GCP methods, and 72% and 84% for the two PLRA methods. Progression rates increased with greater variability with the three GCP methods and decreased with all other methods. The time to detect confirmed progression was longest for the PLRA methods and shortest for the CIGTS and GCP methods. Under the moderate-variability condition, all methods yielded high specificity. The AGIS, CIGTS, and one of the GCP and PLRA methods were relatively resistant to high variability and maintained high specificities. CONCLUSIONS: The AGIS and CIGTS methods had high specificity, but classified fewer cases of progression than the other methods. The GCP methods determined progression earliest; however, they were generally not as specific. Methods based on PLRA were specific but times to confirmed progression were the longest.

Computer Simulation↗
PubMed1995

Multiple sclerosis progression in a natural history study: predictive value of cerebrospinal fluid free kappa light chains.

OBJECTIVES: To determine the relationship between baseline CSF immunologic abnormalities and MS disease progression; To determine progression rates in an untreated, recently-diagnosed MS sample using several validated clinical measures. BACKGROUND: CSF immune abnormalities are common in MS but have not been linked to disease progression. DESIGN METHODS: Thirty-six patients with definite (n = 28), probable (n = 2), or possible (n = 6) MS were studied prospectively. Baseline CSF was analyzed for free kappa and lambda light chains, myelin basic protein, IgG synthesis rate, and IgG index. MS patients were entered into the study within 5 years of symptom onset and examined semiannually for as long as 53.4 months (median length of follow up 38.9 months). MS progression was defined as sustained worsening on the following clinical measurement instruments: the Expanded Disability Status Scale (EDSS), the Ambulation Index (AI), the 9 Hole Peg Test (9HT) and the Box and Blocks test (BBT). Kaplan-Meier estimates of disease progression were calculated and the relationship between baseline CSF values and disease progression was determined using Cox proportional hazards regression models. RESULTS: By 36 months, 33% (95% CI = 10.3, 55.7) of patients had progressed on EDSS and 49.7% (95% CI = 27.7, 71.7) had progressed on at least one of the outcome measures. Patients with CSF free kappa chain levels in the upper quartile had a significantly higher risk of progression on EDSS (Hazard Ratio 3.78; p = 0.04) and 9HT (Hazard Ratio 10.77, p = 0.04). CONCLUSIONS: In this study, CSF free kappa light chains predicted subsequent physical deterioration in prospectively evaluated MS patients. If this is confirmed by larger studies, then CSF free kappa light chains could serve as a target for intervention in therapeutic trials.

Adolescent↗
PubMed2005

Role of viral evolutionary rate in HIV-1 disease progression in a linked cohort.

BACKGROUND: The actual relationship between viral variability and HIV disease progression and/or non-progression can only be extrapolated through epidemiologically-linked HIV-infected cohorts. The rarity of such cohorts accents their existence as invaluable human models for a clear understanding of molecular factors that may contribute to the various rates of HIV disease. We present here a cohort of three patients with the source termed donor A--a non-progressor and two recipients called B and C. Both recipients gradually progressed to HIV disease and patient C has died of AIDS recently. By conducting 15 near full-length genome (8.7 kb) analysis from longitudinally derived patient PBMC samples enabled us to investigate the extent of molecular factors, which govern HIV disease progression. RESULTS: Four time points were successfully amplified for patient A, 4 for patient B and 7 from patient C. Using phylogenetic analysis our data confirms the epidemiological-linkage and transmission of HIV-1 from a non-progressor to two recipients. Following transmission the two recipients gradually progressed to AIDS and one died of AIDS. Viral divergence, selective pressures, recombination, and evolutionary rates of HIV-1 in each member of the cohort were investigated over time. Genetic recombination and selective pressure was evident in the entire cohort. However, there was a striking correlation between evolutionary rate and disease progression. CONCLUSION: Non-progressing individuals have the potential to transmit pathogenic variants, which in other host can lead to faster HIV disease progression. This was evident from our study and the accelerated disease progression in the recipient members of he cohort correlated with faster evolutionary rate of HIV-1, which is a unique aspect of this study.

Acquired Immunodeficiency Syndrome↗
PubMed1995

Intravesical bacillus Calmette-Guérin therapy prevents tumor progression and death from superficial bladder cancer: ten-year follow-up of a prospective randomized trial.

PURPOSE: Superficial bladder tumors (stage Ta, T1, and Tis) may progress to invade the bladder muscle and cause death from metastatic cancer. Transurethral tumor resection (TURB) is the standard therapy for such tumors, but surgery alone may not prevent tumor progression. Intravesical therapy is widely used as an adjunct to TURB. Bacillus Calmette-Guérin (BCG) is the most active intravesical agent, but whether BCG prevents tumor progression and death from bladder cancer is unknown. PATIENTS AND METHODS: Between 1978 and 1981, 86 high-risk patients with superficial bladder cancer were randomly assigned to receive either TURB (n = 43) or TURB plus BCG (n = 43). Adverse tumor features for progression were equally distributed between the two groups. BCG was administered weekly for 6 weeks. Patients were evaluated every 3 to 6 months thereafter for progression to muscle invasion or metastasis. Control (TURB) patients with recurrent superficial tumors were eligible for crossover to the BCG arm. All patients have been monitored until event or for a minimum of 10 years (range, 10 to 14). RESULTS: The 10-year progression-free rate was 61.9% (95% confidence interval [CI], 47.2% to 76.7%) for patients treated with BCG and 37% (95% CI, 22.9% to 53.1%) for control patients. The median progression-free interval was not reached for the BCG group and was 46 months for the control group (P = .0063). Of 18 control patients crossed over to BCG (median, 29 months), 15 did not show tumor progression. TURB plus BCG resulted in a 10-year disease-specific survival rate of 75%, compared with 55% with TURB alone (P = .03). CONCLUSION: This study shows that intravesical therapy with BCG delays tumor progression and death from tumor in patients who present with superficial bladder cancer.

BCG Vaccine↗
PubMed2001

Use of CA-125 to define progression of ovarian cancer in patients with persistently elevated levels.

PURPOSE: To determine an accurate definition for progression of ovarian cancer in patients with a persistently elevated serum CA-125. PATIENTS AND METHODS: A retrospective analysis was performed on 300 patients with epithelial ovarian carcinoma with at least one measurement of CA-125. The date of progression according to clinical or radiologic criteria was ascertained in the 88 patients with persistently elevated CA-125 levels (> 23 U/mL). This was compared with the date of progression according to CA-125, defined as the date on which the CA-125 level first increased to >or= twice its nadir level, confirmed by a second sample also >or= twice the nadir. RESULTS: Eighty of the 88 patients had evidence of progression by both standard and CA-125 criteria, giving a sensitivity of 94%. In six of these patients, no sample was taken to confirm CA-125 doubling. In 13 patients, CA-125 doubling occurred after the date of clinical progression. Only one patient had a false-positive prediction of progression according to CA-125; the patient died as a result of a myocardial infarct before evidence of clinical progression. CONCLUSION: In patients whose CA-125 level decreases to normal after chemotherapy, a doubling from the upper limit of normal has been shown to predict progression. In those with persistently elevated levels, doubling of CA-125 from its nadir level has now been shown to accurately define progression. If confirmed, these CA-125 criteria should be used as additional end points in clinical trials.

CA-125 Antigen↗
PubMed2006

Comparison of CA-125 and standard definitions of progression of ovarian cancer in the intergroup trial of cisplatin and paclitaxel versus cisplatin and cyclophosphamide.

PURPOSE: A definition for progression of ovarian cancer has been proposed based on either a confirmed doubling of CA-125 levels from the upper limit of normal or from the nadir level if levels are persistently elevated. Retrospectively, we determined whether the use of this CA-125 definition in a randomized trial would have shown the same magnitude of difference between the treatment arms as was shown when the standard progression definition was used. PATIENTS AND METHODS: A retrospective analysis was performed on 680 patients in the Taxol Intergroup Trial with advanced epithelial ovarian carcinoma, of whom 628 were assessable according to CA-125. The date of progression according to clinical or radiologic criteria was compared with the date of progression according to CA-125. RESULTS: Of the 628 patients assessable for both definitions, 556 clinical or radiologic progressions were determined compared with 389 according to the CA-125 definition. There was a highly significant difference in the hazard of progression between the paclitaxel and cisplatin arm (TP) compared with the cyclophosphamide and cisplatin arm (CP) when either standard or CA-125 criteria were used to define progression (standard, P = .002; CA-125, P = .011). The hazard ratio of TP/CP over time was similar when comparing the different methods of defining progression. CONCLUSION: The results of this analysis show that the magnitude of the therapeutic benefit was similar whether CA-125 or standard criteria were used to define progression.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Detrimental effects of tumor progression on cognitive function of patients with high-grade glioma.

PURPOSE: There is growing recognition that the primary cause of cognitive deficits in adult patients with primary brain tumors is the tumor itself and more significantly, tumor progression. To assess the cognitive performance of high-grade glioma patients, prospectively collected cognitive performance data were analyzed. PATIENTS AND METHODS: We studied 1,244 high-grade brain tumor patients entered onto eight consecutive North Central Cancer Treatment Group treatment trials that used radiation and nitrosourea-based chemotherapy. Imaging studies and Folstein Mini-Mental State Examination (MMSE) scores recorded at baseline, 6, 12, 18, and 24 months were analyzed to assess tumor status and cognitive function over time. RESULTS: The proportion of patients without tumor progression who experienced clinically significant cognitive deterioration compared with baseline was stable at 6, 12, 18, and 24 months (18%, 16%, 14%, and 13%, respectively). In patients without radiographic evidence of progression, clinically significant deterioration in MMSE scores was a strong predictor of a more rapid time to tumor progression and death. At evaluations preceding interval radiographic evidence of progression, there was significant deterioration in MMSE scores for patients who were to experience progression, whereas the scores remained stable for the patients who did not have tumor progression. CONCLUSION: The proportion of high-grade glioma patients with cognitive deterioration over time is stable, most consistent with the constant pressure of tumor progression over time. Although other factors may contribute to cognitive decline, the predominant cause of cognitive decline seems to be subclinical tumor progression that precedes radiographic changes.

Adult↗