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PubMed2005

Glaucomatous visual field progression with frequency-doubling technology and standard automated perimetry in a longitudinal prospective study.

PURPOSE: To compare frequency-doubling technology (FDT) perimetry with standard automated perimetry (SAP) for detecting glaucomatous visual field progression in a longitudinal prospective study. METHODS: One eye of patients with open-angle glaucoma was tested every 6 months with both FDT and SAP. A minimum of 6 examinations with each perimetric technique was required for inclusion. Visual field progression was determined by two methods: glaucoma change probability (GCP) analysis and linear regression analysis (LRA). For GCP, several criteria for progression were used. The number of locations required to classify progression with FDT compared with SAP, respectively, was 1:2 (least conservative), 1:3, 2:3, 2:4, 2:6, 2:7, 3:6, 3:7, and 3:10 (most conservative). The number of consecutive examinations required to confirm progression was 2-of-3, 2-of-2, and 3-of-3. For LRA, the progression criterion was any significant decline in mean threshold sensitivity over time in each of the following three visual field subdivisions: (1) all test locations, (2) locations in the central 10 degrees and the superior and inferior hemifields, and (3) locations in each quadrant. Using these criteria, the proportion of patients classified as showing progression with each perimetric technique was calculated and, in the case of progression with both, the differences in time to progression were determined. RESULTS: Sixty-five patients were followed for a median of 3.5 years (median number of examinations, 9). For the least conservative GCP criterion, 32 (49%) patients were found to have progressing visual fields with FDT and 32 (49%) patients with SAP. Only 16 (25%) patients showed progression with both methods, and in most of those patients, FDT identified progression before SAP (median, 12 months earlier). The majority of GCP progression criteria (15/27), classified more patients as showing progression with FDT than with SAP. Contrary to this, more patients showed progression with SAP than FDT, when analysed with LRA; e.g., using quadrant LRA 20 (31%) patients showed progression with FDT, 23 (35%) with SAP, and only 10 (15%) with both. CONCLUSIONS: FDT perimetry detected glaucomatous visual field progression. However, the proportion of patients who showed progression with both FDT and SAP was small, possibly indicating that the two techniques identify different subgroups of patients. Using GCP, more patients showed progression with FDT than with SAP, yet the opposite occurred using LRA. As there is no independent qualifier of progression, FDT and SAP progression rates vary depending on the method of analysis and the criterion used.

Disease Progression↗
PubMed2006

The natural history of multiple sclerosis: a geographically based study 9: observations on the progressive phase of the disease.

The clinical features of relapses and progression largely define multiple sclerosis phenotypes. A relapsing course is followed by chronic progression in some 80% of cases within 2 decades. The relationship between these phases and long-term outcome remains uncertain. We have analysed these clinical features within a well-studied natural history cohort with mean follow-up of 25 years. For the entire cohort, median times to reach Disability Status Scale (DSS) 6, 8 and 10 were 12.7, 20.6 and 43.9 years, respectively. Among 824 attack-onset patients, the great majority entered a progressive phase with a mean time to progression of 10.4 years. The effects of relapses often cloud the clinical onset of progression. However, there are circumstances where onset of progression is early, relatively discrete and identifiable at DSS of 2 or less. Three subgroups allow for clarity of outcome comparison and they are (i) cases of primary progressive (PP) disease, (ii) attack-onset disease where only a single attack has occurred before onset of progression (SAP) and (iii) secondary progressive (SP) disease where recovery from relapses allows recognition of the earliest clinical stages when progression begins. Here we compare survival curves in these three groups. Among cohorts of SAP (n = 140), PP (n = 219) and SP (n = 146) where progression was stratified by DSS at its onset, there was no difference in time to DSS 6, 8 and 10. These findings demonstrate that the progressive course is independent of relapses either preceding the onset of relapse-free progression or subsequent to it. Among SAP patients, the degree of recovery from the single defining exacerbation had no significant effect on outcome. The site of the original attack was not usually where progression began. The relatively stereotyped nature of the progressive phase seen in all progressive phenotypes suggests regional and/or functional differential susceptibility to a process that appears degenerative in nature. The highly prevalent distal corticospinal tract dysfunction in progressive disease and the pathologically demonstrated selective axonal loss seen in this tract raises the possibility of a dying back central axonopathy, at least in part independent of plaque location or burden. Despite considerable individual variation, the progressive course of disability seen in groups of PP, SAP and SP-DSS2 is similarly stereotyped in quality and pace and may entail mechanisms common to all forms of progressive multiple sclerosis. The possibility that this is the primary process in some cases must be considered.

Adolescent↗
PubMed2002

Spatial and temporal processing of threshold data for detection of progressive glaucomatous visual field loss.

OBJECTIVE: To evaluate the effect of spatial and temporal filtering of threshold visual field data on the ability of pointwise linear regression (PLR) to detect progressive glaucomatous visual field loss. METHODS: Longitudinal visual field data (Full-Threshold Program 30-2 test point pattern) were simulated using a computer model of glaucomatous visual field progression. This approach permitted construction of a "gold standard" because matching visual field data without variability could be generated and analyzed. Four clustered progressive defects were produced, consisting of 2, 3, 9, and 18 locations, respectively, each with progression rates of -1 and -2.5 dB/y. Pointwise linear regression was used to identify progressive test locations (criterion for progression of statistically significant slope of < or =-1 dB/y, P<.05). Each visual field series was analyzed after the following 3 procedures: (1) no filtering (unprocessed data), (2) Gaussian spatial possessing (3 x 3 grid), and (3) temporal processing (2 field moving average). The effect of spatial and temporal processing on PLR discriminatory power for progression detection was quantified by comparison with the gold standard. RESULTS: Spatial processing reduced PLR sensitivity to levels below that achieved for analysis of unprocessed data for small progressive defects (< or =9 locations) or at the low true progression rate (-1 dB/y). Under these conditions, spatial processing caused small PLR specificity improvement. Spatial processing only improved PLR sensitivity above unprocessed levels when progressive defects were large and changing rapidly (progression rate of -2.5 dB/y). Temporal processing gave consistent PLR improvement in sensitivity for all defect sizes and true progression rates. Pointwise linear regression sensitivity gain provided by temporal processing allowed progression to be detected 2 to 3 visual fields earlier than for analysis of raw data. Specificity dropped slightly as a result of temporal processing but remained at 89% or above for all conditions studied. CONCLUSIONS: Gaussian spatial processing reduces PLR discriminatory power with low true progression rates or small progressive defect sizes and, therefore, is of limited use for detection of progressive visual field loss. Temporal processing improves the sensitivity of PLR and reduces the number of tests required to detect progressive loss with minimal loss of specificity. CLINICAL RELEVANCE: Image processing techniques can be applied to threshold visual field data to enhance sensitivity or specificity of PLR for the determination of progressive change. This investigation demonstrates that temporal processing may assist with the detection of significant progressive visual field loss with fewer test results than unprocessed data.

Computer Simulation↗
PubMed1999

Pattern of progression and survival in hormonally treated metastatic prostate cancer.

BACKGROUND: Patients with prostate cancer generally respond to androgen ablation therapy, but progression to androgen-independence is frequently observed. To further evaluate disease progression, the pattern of progression and survival in hormonally treated metastatic prostate cancer was examined. METHODS: One hundred and ninety-three patients with untreated metastatic prostate cancer (TxNxM ) who received endocrine therapy between 1986 and 1995 were included in the present study. The pattern of progression was evaluated in these patients. RESULTS: One hundred and eighteen of the 193 patients (61.1%) had disease progression: 33 had local progression, 73 had distant progression and 12 had distant with local progression. Patients with only local progression had a longer interval to disease progression and longer survival than those with distant progression. The interval from disease progression to death in patients with local progression was longer than in those with distant progression. The patients whose prostate-specific antigen (PSA) had not been normalized 3 months after the start of endocrine therapy had a tendency to progression either into the prostate or into distant sites. Patients with extent of disease (EOD) scores of 3 and 4 progress, especially to distant sites, after endocrine treatment. CONCLUSIONS: In untreated metastatic prostate cancer, patients with a poor response of PSA levels and patients with a high volume of bone metastasis (i.e. EOD 3, 4) were in the high-risk group for progression, especially to distant sites. Progression into distant sites was a poor prognostic factor for patients with recurrence to endocrine therapy.

Aged↗
PubMed2002

Short wavelength automated perimetry, frequency doubling technology perimetry, and pattern electroretinography for prediction of progressive glaucomatous standard visual field defects.

PURPOSE: To evaluate the clinical use of a test battery of short wavelength automated perimetry (SWAP), frequency doubling technology perimetry (FDT), and pattern electroretinography (PERG) in predicting progressive glaucomatous visual field defects on standard automated perimetry (SAP). STUDY DESIGN: A prospective, longitudinal, observational case series. PARTICIPANTS: One hundred and fifty-two patients with primary open-angle glaucoma (POAG) with bilateral glaucomatous visual field defects on SAP were followed at 6-month intervals over a period of 30 months. MAIN OUTCOME MEASURES: Short wavelength automated perimetry, FDT, and PERG results were compared between POAG eyes with and without progressive field loss on SAP. These two groups were used to evaluate whether PERG, SWAP, and/or FDT is predictive of future progression of field loss on SAP. RESULTS: Using the criteria of progressive field loss on SAP defined by the Collaborative Normal Tension Glaucoma Study, 54 eyes (study group) of 54 POAG patients showed progressive defects, whereas 84 eyes (control group) of 84 POAG patients showed no progression. Only 11.1% (6 of 54) of the eyes with a progression of field loss on SAP showed no increase of deficits on the three functional tests before progression. Short wavelength automated perimetry detected early progressive defects on SAP in 43 of the 54 eyes (79.6%). Of these 54 POAG eyes, FDT showed progressive deficits in 40 eyes (74.1%), whereas PERG amplitude P1N2 showed progressive deficits in 35 eyes (64.8%) before progression of field loss on SAP. A test battery consisting of SWAP and PERG P1N2-amplitude was able to detect 88.9% of eyes before a prediction of field loss on SAP. When comparing the results of the two functional tests, SWAP and FDT in the 84 eyes without progression of field loss on SAP between baseline and at 30 months, SWAP and FDT showed progressive deficits in 34.5% and 35.7%, respectively. CONCLUSIONS: All three tests (SWAP, FDT, and PERG) have been successful in detecting glaucoma eyes with a future progression of standard visual field defects. A test battery of SWAP and PERG P1N2-amplitude improved the power to predict these progressive defects on SAP. It remains to be seen whether the long-term follow-up in POAG eyes will improve the false-positive rate of SWAP and FDT.

Disease Progression↗
PubMed2002

Correlation of visual field progression between eyes in patients with open-angle glaucoma.

PURPOSE: To investigate the correlation of visual field progression between eyes in patients with chronic forms of open-angle glaucoma (OAG) and to determine risk factors for progression. DESIGN: Retrospective observational case series. PARTICIPANTS: One hundred fifty-two patients seen between April and November 2000 undergoing bilateral treatment for at least 2 years for OAG and who were followed with standard automated perimetry at the University of Washington Medical Center Eye Clinic. METHODS: Visual field progression was defined using criteria modified from Anderson and Advanced Glaucoma Intervention Study (AGIS) scoring. Progression from a normal to an abnormal visual field required abnormality of two of three criteria (glaucoma hemifield test, corrected pattern standard deviation, and total deviation plot abnormality) on at least two consecutive fields. For abnormal visual fields, criteria for progression were modified from Anderson and were based on worsening observed at three adjacent points on the total deviation plot on at least two consecutive fields. Another definition of progression was a change in AGIS score of four or more points. MAIN OUTCOME MEASURES: Visual field progression. RESULTS: The mean follow-up period was 7.5 +/- 3.6 years. Fifty-four patients (35.5%) showed progression of the more severely affected of the two eyes (worse eye), and 37 patients (24.3%) had progression in the less affected fellow (better) eye. Among these patients, 24 (15.8%) had bilateral progression (44% and 65% of worse and better eyes with progression, respectively). The between-eye correlation for progression was statistically significant (chi-square with Yates' continuity correction; chi = 16.7, P = 0.00004; R = 0.348, P = 0.00001). The Kaplan-Meier estimates at 10 years for progression in the worse eye, the better eye, and both eyes was 44%, 33%, and 21%, respectively. CONCLUSIONS: Between-eye correlation of visual field progression in patients with chronic OAG was statistically and clinically significant. Patient-specific factors may play an important role in visual field progression in OAG. Documented progression of visual field loss in one eye may prompt the physician to consider reducing the target intraocular pressure in both eyes.

Chronic Disease↗
PubMed1998

Increasing peripapillary atrophy is associated with progressive glaucoma.

OBJECTIVE: This study aimed to determine the incidence and degree of progression of peripapillary atrophy in progressive and nonprogressive glaucoma. STUDY DESIGN: A retrospective cohort study. PARTICIPANTS: A total of 75 eyes of 75 patients were examined. MAIN OUTCOME MEASURES: Qualitative assessment of optic disc, peripapillary atrophy,and visual field change was performed by three experienced, masked, independent observers. METHODS: Rim-disc area ratio and peripapillary atrophy-disc area ratio were measured at baseline and follow-up with computer-aided planimetry. RESULTS: Among 75 eyes studied with an average duration of follow-up of 8 years (range, 4-19 years), 33 (44%) showed progressive optic disc damage. Twenty-one (64%) of 33 eyes with progressive disc damage showed peripapillary atrophy progression, and 7 (17%) of 42 eyes without progressive disc damage showed peripapillary atrophy progression; this difference was significant (P < 0.01). In groups with and without peripapillary atrophy, no statistically significant differences were found for mean intraocular pressure, baseline rim-disc area ratio, or baseline peripapillary atrophy-disc area ratio. However, optic disc progression and visual field progression were statistically more frequent in the group with peripapillary atrophy progression (75% and 54%, respectively) than in the group without peripapillary atrophy progression (26% and 11%, respectively) (P < 0.01). There was a statistically significant correlation between measurements of peripapillary atrophy area increase and disc rim loss over time (r = -0.35, P = 0.002). CONCLUSION: Progression of peripapillary atrophy is associated with progressive optic disc damage and progressive visual field loss in glaucoma and may be used as a marker for progressive glaucomatous damage.

Adult↗
PubMed1998

Variable progression of HIV-associated dementia.

A consecutive series of 71 patients diagnosed with HIV-associated dementia (HAD) (1984-1994) were studied to characterize the clinical course of HAD, and to identify predictive markers of rapid neurologic progression. Neurologic progression rate was determined from the change in the Memorial Sloan Kettering (MSK) dementia severity score from diagnosis to death. Those with the most rapid progression in neurologic disability were compared with those with slow or no progression. Autopsy material was immunostained for macrophage activation markers and gp41 in 30 individuals. Median survival was 3.3 months and 6.1 months for rapid-progression and no-progression patients, respectively. Rapid progression was associated with injection drug use but not with race, gender, or age. CD4+ cell counts were lower at diagnosis among rapid-progression than no-progression patients but no differences in AIDS-defining illnesses or patterns of antiretroviral therapy were found. At presentation, rapid-progression patients had more prominent symptoms of mental slowing than those with no progression; however, no other clinical features, CSF, or imaging features distinguished the groups. Less abundant macrophage activation in both basal ganglia and midfrontal gyrus regions, as judged by HAM56 immunostaining, was noted in 9 no-progression patients, compared with 12 rapid-progression patients. Neurologic progression and survival with HAD is highly variable. A significant proportion of individuals with dementia have prolonged survival of more than 12 months and remain cognitively stable. A history of injection drug use and presentation with prominent psychomotor slowing is associated with more rapid neurologic progression, and these patients tend to show more abundant macrophage activation within the CNS.

AIDS Dementia Complex↗
PubMed2006

Optic disc and visual field progression in ocular hypertensive subjects: detection rates, specificity, and agreement.

PURPOSE: To examine the detection rates, specificity, and agreement between visual field (VF) progression and Heidelberg Retina Tomograph (HRT; Heidelberg Engineering, GmbH, Heidelberg, Germany) rim area (RA) progression in subjects with ocular hypertension (OHT). METHODS: One hundred ninety-eight OHT and 21 control subjects were examined prospectively (1994-2001) with regular Humphrey VF (Carl Zeiss Meditec, Inc., Dublin, CA) and HRT testing. Point-wise linear regression (PLR) of sensitivity/time was used to assess VF progression, using standard and three-omitting (less stringent and stringent) criteria. The change in HRT-detected progression was assessed by linear regression of sectoral RA/time, defined as slope>1%/year, with significance level tailored according to series variability. Less stringent and stringent criteria were tested. Specificity was estimated by the proportions of control subjects with disease progression and significantly improving subjects (all). Agreement between disc and field progression in the subjects with OHT was assessed with specificities matched for both VF and HRT. RESULTS: Specificity for VF PLR was estimated to be 85.7% to 95.4% when standard criteria were used, and for RA/time to be 88.1% to 90.5% with the less-stringent criteria. In this comparison, 21.2% progressed by RA alone and 20.2% by VF alone, and 12.1% progressed by both RA and VF. Specificity was estimated to be 95.2% to 98.2% for both VF PLR and RA/time, using the three-omitting criteria and the stringent RA/time criteria, respectively. In this comparison, 8.6% progressed by RA alone, 15.1% by VF alone, and 3.5% by both RA and VF. CONCLUSIONS: A relatively high frequency of detected disease progression was observed with either method, with progression by VF occurring at least as frequently as progression by RA. Poor agreement between RA and VF progression was observed regardless of the specificity of the progression criteria. The results indicate that, in patients with ocular hypertension, monitoring of both VF and optic disc is necessary, as agreement between optic disc and VF progression is the exception rather than the rule.

Adult↗
PubMed1999

Predictors of cancer progression in T1a prostate adenocarcinoma.

BACKGROUND: The biologic behavior of T1a prostate adenocarcinoma is variable. A critical issue in the management of patients with T1a prostate adenocarcinoma is to distinguish those who will develop cancer progression from those who will not. Predictive factors that identify those at high risk of cancer progression are needed to stratify patients for treatment. In the current study the authors attempted to identify such predictors of cancer progression in a large series of untreated patients with lengthy follow-up. METHODS: The authors studied 102 patients who were diagnosed with T1a prostate adenocarcinoma (incidental tumor involving < or = 5% of the resected prostatic tissue) at the time they underwent transurethral resection of the prostate (TURP) at the Mayo Clinic between 1960-1970. None of these patients were treated. Patient ages ranged from 48-91 years (mean +/- standard deviation, 69 +/- 7 years). The average weight of the resected prostate tissue was 24 +/- 18 g (range, 3-115 g; median, 18 g). Tumor volume was measured by the grid method. Cox proportional hazards models were used to identify factors associated with cancer progression. Survival curves were estimated using the Kaplan-Meier method. RESULTS: Five-year and 10-year progression free survival rates were 93% and 87%, respectively. During the mean follow-up of 9.5 +/- 6.8 years (range, 0.3-31 years; median, 9.0 years), 14 patients developed clinical cancer progression, including 5 patients with systemic progression (1 with distant metastases and 4 who died of prostate adenocarcinoma). The interval from diagnosis to clinical cancer progression ranged from 1-23 years (mean, 7.3 years). The amount of resected prostate tissue (TURP weight) was associated with progression (P = 0.04). Patients with a TURP weight > or = 30 g had 100% progression free survival at 10 years compared with a progression free survival rate of 73% in patients with a TURP weight < 12 g. Gleason score, tumor volume, number of chips involved by tumor, number of tumor foci, and the presence of high grade prostatic intraepithelial neoplasia were not significant in predicting cancer progression. There was a trend toward a worse prognosis with the increasing number of chips involved by cancer (P = 0.16). Patients with < 3 chips involved by cancer had a 88% 10-year progression free survival rate compared with 73% in patients with > or = 3 chips involved by cancer. CONCLUSIONS: The clinical course of T1a prostate adenocarcinoma is variable. If left untreated, a small but significant proportion of patients are at risk for disease progression and death. However, the current study found that patients with a TURP weight > or = 30 g have an excellent prognosis and can be managed conservatively.

Adenocarcinoma↗
PubMed2026

Continuous administration of lenvatinib after first documented disease progression in patients with radioiodine-refractory thyroid cancer.

PURPOSE: To determine the efficacy and safety of lenvatinib beyond first documented disease progression (LBP) and prognostic factors after progression in patients with radioiodine-refractory thyroid cancer. METHODS: This retrospective study included adults with radioiodine-refractory thyroid cancer who received lenvatinib between January 2012 and November 2023 and continued treatment after initial RECIST 1.1 progression. Patients who subsequently received other multikinase inhibitors or selective targeted therapies were excluded. Time to second treatment failure (second TTF) was defined as time from initial progression to permanent lenvatinib discontinuation for any reason; second progression-free survival (second PFS) as time from initial progression to subsequent radiographic progression or death; and post-progression survival (PPS) as time from initial progression to death. Outcomes were estimated by Kaplan&#x2013;Meier methods, and prognostic factors were explored by Cox regression. Safety was assessed. RESULTS: Twenty-four patients met the eligibility criteria for LBP. The objective response rate after progression was 0%, whereas the disease control rate was 50.0%. Median second PFS and second TTF were 6.0 months and 8.0 months, respectively. Median PPS was 14.8 months. At 12 months after initial progression, 37.5% of patients remained on lenvatinib and 56.5% were alive. Baseline progressive disease at initial progression (tumor burden returning to or exceeding the pretreatment baseline) was associated with shorter second TTF, with similar trends for second PFS and PPS. The most common adverse events were hypertension, proteinuria, peripheral edema, and renal dysfunction. CONCLUSION: Continuation of lenvatinib beyond disease progression achieved modest additional disease control with acceptable safety in selected patients. In settings where access to subsequent-line systemic therapies is limited or no actionable targets are identified, LBP may serve as a pragmatic bridging approach for carefully selected patients.

Humans↗
PubMed2004

Disease progression in contralateral carotid artery is common after endarterectomy.

OBJECTIVE: Although the North American Symptomatic Carotid Endarterectomy Trial (NASCET) and the Asymptomatic Carotid Atherosclerosis Study (ACAS) have helped to define the role of carotid endarterectomy (CEA) for both symptomatic and asymptomatic lesions, the role of surveillance of the contralateral carotid artery remains unclear. The purpose of this study was to determine the progression of contralateral carotid artery disease with serial duplex ultrasound scans after CEA compared with the recurrent stenosis rate for the carotid artery ipsilateral to the CEA. METHODS: From January 1990 to December 2000, 473 CEA procedures were performed at a Veterans Affairs Medical Center. From this group we identified 279 patients who had undergone first-time CEA, as well as preoperative duplex scanning and postoperative duplex scanning at least once, in the vascular laboratory. At each visit stenosis of the internal carotid artery (ICA) was categorized as none (0%-14%), mild (15%-49%), moderate (50%-79%), severe (80%-99%), or occluded. Analysis of probability of freedom from progression was determined. Progression was defined as an increase in ICA stenosis 50% or greater or increase to a higher category of stenosis if baseline was 50% or greater. The Cox proportional hazards model was used for data analysis. RESULTS: Mean patient age was 65.7 years (range, 33-100 years). The 1024 carotid duplex ultrasound scanning examinations performed (mean, 3.7; range, 2-13) included the last study done before the index CEA and all studies done after the CEA. Mean follow-up was 27 months (range, 1-137 months). Forty-six patients were found to have contralateral carotid occlusion at initial duplex scanning, and were therefore excluded from the contralateral progression analysis. Contralateral progression was more frequent than ipsilateral recurrent stenosis at long-term follow-up (P <.01). Annual rates of "any progression" and "progression to severe stenosis or occlusion" were 8.3% and 4.4%, respectively, for contralateral arteries, and 4.3% and 2.4%, respectively for ipsilateral arteries. As a result of surveillance, 43 contralateral CEAs (19% of initial cohort) were performed. Carotid stenosis regressed in 25 arteries (10.7%). Baseline clinical and demographic factors did not predict disease progression. Baseline contralateral stenosis did not predict time to "any progression," but was a strong predictor of "progression to severe stenosis or occlusion" (P <.001). CONCLUSIONS: After CEA, we identified an 8.3% annual rate of progression of contralateral carotid artery stenosis and a 4.4% annual rate of progression to severe stenosis or occlusion. Baseline contralateral stenosis was significantly predictive of progression to severe stenosis or occlusion. Clinical and demographic factors were not helpful in predicting which patients would have disease progression. These data may help in assessing the cost effectiveness of duplex scanning surveillance after CEA.

Adult↗
PubMed1996

A heterogeneous pattern of progression in endocrine-treated patients with prostate cancer.

Prostatic carcinoma often shows different behavior in the primary site than in the metastases after endocrine treatment. The pattern of disease progression was evaluated in prostate cancer patients. Two hundred and sixty consecutive patients were observed following the initiation of endocrine treatment (11 patients with stage T1 disease, 42 with stage T2 70 with stage T3, 11 with N + M0 and 126 with stage M1 disease). Of the 117 patients whose disease progressed, 100 could be evaluated in terms of the pattern of disease progression. Twenty-two (64.7%) of the 34 patients with stage T1-3N0M0 showed a pattern of local progression. On the other hand, 56 (84.8%) of the 66 patients with stage N + or M1 experienced a pattern of distant progression. Patients with only distant progression numbered 36 cases and patients with local progression and distant progression numbered 20 cases. Most of the distant progressions appeared in bone site. Local progression was observed in only 30 (45.5%) patients with stage N + or M1 disease. In patients with localized disease (T1-3N0M0), both the interval to disease progression and the time to cancer death from the start of disease progression were significantly longer than those of patients with stage N + or M1. However, once bone metastasis occurred, the disease tended to progress rapidly. There was no significant difference between the interval to cancer death after the appearance of bone metastasis in patients with initially localized stages (T1-3N0M0) and the time to cancer death after disease progression in patients with metastatic disease (N + or M1). The study shows a heterogenous behavior of the prostatic tumor after endocrine treatment. This suggests that metastases and primary tumor have different clonal compositions. The study also supports the idea that there is a preferential environment for the growth of prostatic carcinoma cells in bone sites.

Aged↗
PubMed2006

White matter lesions are associated with progression of medial temporal lobe atrophy in Alzheimer disease.

BACKGROUND AND PURPOSE: Medial temporal lobe atrophy (MTA) is a hallmark of Alzheimer disease (AD). Its progression is often seen during the course of AD, but its frequency and risk factors remain unclear. METHODS: We investigated MTA in 35 patients with AD from whom sequential magnetic resonance imaging scans were available. White matter lesions (WML; for the periventricular [PV] and subcortical [SC] regions separately) and MTA were rated semiquantitatively. RESULTS: In approximately two thirds of all patients, progression of MTA was found. The mean MTA progression was 0.8 (standard deviation: 0.5) and 0.3 (standard deviation: 0.4) for patients with or without PVWML at baseline (P=0.01). Patients who showed progression of PVWML over the course of their disease had a significantly higher mean progression of MTA than those without PVWML progression (0.9 [SD: 0.4]) and 0.4 [SD: 0.5]; P=0.01). Patients with PVWML at baseline had a 40-fold increased risk for progression of MTA compared with those without baseline PVWML (odds ratio=40.0, 95% CI=1.3 to 1.2x10(3), P=0.03). Patients with progression of PVWML during the course of the disease had an increased risk for MTA progression (odds ratio=3.7 per unit increase of progression of PVWML, 95% CI=1.1 to 12.9, P=0.04). There was higher risk for progression of MTA for those with progression of PVWML than those without (odds ratio=10.9, 95% CI=1.0 to 122.5, P=0.05). This was not found for SCWML. CONCLUSIONS: Our findings suggest that the presence and the progression of WML are associated with progression of MTA in AD. WML may be a predictor of the course of the disease and a potential treatment target in AD.

Aged↗
PubMed2005

Visual field progression in glaucoma: total versus pattern deviation analyses.

PURPOSE: To compare visual field progression with total and pattern deviation analyses in a prospective longitudinal study of patients with glaucoma and healthy control subjects. METHODS: A group of 101 patients with glaucoma (168 eyes) with early to moderately advanced visual field loss at baseline (average mean deviation [MD], -3.9 dB) and no clinical evidence of media opacity were selected from a prospective longitudinal study on visual field progression in glaucoma. Patients were examined with static automated perimetry at 6-month intervals for a median follow-up of 9 years. At each test location, change was established with event and trend analyses of total and pattern deviation. The event analyses compared each follow-up test to a baseline obtained from averaging the first two tests, and visual field progression was defined as deterioration beyond the 5th percentile of test-retest variability at three test locations, observed on three consecutive tests. The trend analyses were based on point-wise linear regression, and visual field progression was defined as statistically significant deterioration (P < 5%) worse than -1 dB/year at three locations, confirmed by independently omitting the last and the penultimate observation. The incidence and the time-to-progression were compared between total and pattern deviation analyses. To estimate the specificity of the progression analyses, identical criteria were applied to visual fields obtained in 102 healthy control subjects, and the rate of visual field improvement was established in the patients with glaucoma and the healthy control subjects. RESULTS: With both event and trend methods, pattern deviation analyses classified approximately 15% fewer eyes as having progressed than did the total deviation analyses. In eyes classified as progressing by both the total and pattern deviation methods, total deviation analyses tended to detect progression earlier than the pattern deviation analyses. A comparison of the changes observed in MD and the visual fields' general height (estimated by the 85th percentile of the total deviation values) confirmed that change in the glaucomatous eyes almost always comprised a diffuse component. Pattern deviation analyses of progression may therefore underestimate the true amount of glaucomatous visual field progression. CONCLUSIONS: Pattern deviation analyses of visual field progression may underestimate visual field progression in glaucoma, particularly when there is no clinical evidence of increasing media opacity. Clinicians should have access to both total and pattern deviation analyses to make informed decisions on visual field progression in glaucoma.

Adult↗
PubMed1999

Quantitative and qualitative progression of peripheral arterial disease by non-invasive testing.

There is little information on the progression of peripheral arterial disease (PAD) over time. A series of 508 patients with a prior examination for PAD were contacted and brought in for follow-up to evaluate the natural history of PAD. A total of 85 patients were excluded because they had interventions in both limbs prior to their return visit. Progression was assessed in the remaining 423 patients for a total of 755 limbs, both quantitatively and qualitatively using six categories of PAD severity. There was a modest overall categorical progression of disease: 228 limbs (30.2%) displayed categorical progression, while 172 limbs (22.8%) improved over a 4.6-year average follow-up. Through analysis of quantitative change, it was determined that more quantitative progression occurred than was evident from categorical progression. Two of the three non-invasive tests employed, the ankle/brachial index (ABI) and posterior tibial peak forward flow velocity (peak PT), showed statistically significant progression during follow-up: mean ABI change = -0.019, 95% confidence interval (CI)= -0.031 to -0.007; mean peak PT change = -2.32 cm/s, 95% CI = -3.20 to -1.44. The toe/brachial index (TBI) also suggested progression: mean change= -0.013, but the 95% CI included no change. Standard scores (sum of the Z-scores for ABI, peak PT and TBI) were calculated. The standard score progressed approximately 0.34 units (standard deviations), p-value <0.001, over 4.6 years; or about 0.07 standard deviations per year. There were independent and statistically significant (p<0.05) associations between the rate of PAD progression (standard score change) and age, diabetes, classic ('Rose') intermittent claudication, moderate to severe PAD in the same limb, moderate to severe PAD in the contralateral limb and future therapeutic intervention. There were independent and suggestive associations (0.05<p-value<0.15) between PAD progression and pain at rest, mild PAD in the same limb, and mild PAD in the contralateral limb. PAD progression was not associated with gender, atypical claudication, or amputation status. Thus, in this cohort of PAD patients, PAD on average progressed significantly over 4.6 years. This progression was independently related to age, diabetes and several markers of disease severity.

Aged↗
PubMed2001

Defining prostate specific antigen progression after radical prostatectomy: what is the most appropriate cut point?

PURPOSE: The most appropriate definition of biochemical progression after radical prostatectomy and radiation therapy is uncertain. We analyzed the effect of using various prostate specific antigen (PSA) end point definitions for defining biochemical progression after radical prostatectomy and attempted to determine the best PSA cut point to use. Aspects of the American Society for Therapeutic Radiology and Oncology (ASTRO) definition of biochemical failure after radiation therapy are also analyzed in our radical prostatectomy cases. MATERIALS AND METHODS: A total of 2,782 men with clinically localized prostate cancer (cT1-T2) who had undergone radical prostatectomy between 1987 and 1993 were reviewed. All patients had regular PSA determinations from surgery through followup. Analysis was limited to patients who did not receive adjuvant treatment within 90 days of radical prostatectomy. Biochemical, PSA progression-free percent after radical prostatectomy was determined by the Kaplan-Meier method using several PSA cut points, including 0.2, 0.3, 0.4 and 0.5 ng./ml. or greater, as well as 0.4 ng./ml. or greater and increasing. Progression-free percent was also assessed using the ASTRO definition, which is 3 increases in PSA. To determine which PSA level was most appropriate to define progression after radical prostatectomy, the percentage of patients with a continued PSA increase after reaching each cut point was determined. The relationship between the maximum PSA within 3 years of surgery and subsequent development of clinical disease was also assessed. RESULTS: Progression-free percent was dependent on the PSA cut point used. Biochemical progression-free percentages for cut points 0.2, 0.3, 0.4 and 0.5 ng./ml. or greater were 62%, 72%, 76% and 78% at 5 years, and 43%, 54%, 59% and 61% at 10 years, respectively. A subsequent increase in PSA was noted in 49%, 62% and 72% of patients who had PSA 0.2, 0.3 and 0.4 ng./ml., respectively. Subsequent clinical progression (local or systemic) was directly related to the maximum PSA attained within 3 years of radical prostatectomy (p=0.0001). Progression-free percent for definitions requiring multiple increases in PSA were dependent on when the event was said to occur. Backdating of events at or before the first PSA (ASTRO definition) resulted in poorer, short-term progression-free percent (78% at 5 years), with little apparent likelihood of long-term failure (78% at 10 years). Coding the event at the last PSA increase when all event criteria had been met resulted in more realistic progression-free percent estimates (85% at 5 and 59% at 10 years). CONCLUSIONS: Biochemical, PSA progression rates vary markedly depending on the method used to define PSA failure. Methods that require multiple increasing PSA values, for example the ASTRO definition, give misleading results, especially if the event time is backdated. Standards for defining PSA progression would allow more consistent and comparable progression estimates after radical prostatectomy. PSA 0.4 ng./ml. or greater may be the most appropriate cut point to use since a significant number of patients with lower PSA do not have a continued increase in it.

Adult↗
PubMed2004

Varus-valgus alignment in the progression of patellofemoral osteoarthritis.

OBJECTIVE: To test the hypotheses that lateral patellofemoral (PF) osteoarthritis (OA) progression is more common than medial PF OA progression, that varus alignment increases the likelihood of medial PF OA progression, and that valgus alignment increases the likelihood of lateral PF OA progression. METHODS: Patients with knee OA were recruited from the community. Inclusion criteria were definite osteophyte presence (i.e., Kellgren/Lawrence radiographic grade >/=2) in 1 or both knees and at least some difficulty with knee-requiring activity. Varus-valgus alignment (the angle formed by the intersection of the mechanical axes of the femur and tibia) was measured on a full-limb radiograph at baseline. To assess PF OA progression, weight-bearing skyline views of the PF compartment were obtained at baseline and at 18-month followup. Knees with the highest grade of PF narrowing at baseline were excluded from analysis. Logistic regression and generalized estimating equations were used; odds ratios (ORs) were adjusted for age, sex, and body mass index. RESULTS: Lateral PF OA progression, which occurred in 120 (30%) of 397 knees, was more common than was medial PF OA progression, which occurred in 60 knees (15%). Varus (versus nonvarus) alignment increased the odds of PF OA progression isolated to the medial PF compartment (adjusted OR 1.85, 95% confidence interval [95% CI] 1.00-3.44). Valgus alignment increased the odds of PF OA progression isolated to the lateral compartment (adjusted OR 1.64, 95% CI 1.01-2.66). CONCLUSION: Lateral PF OA progression was more common than medial progression, and varus-valgus alignment influenced the likelihood of PF OA progression in a compartment-specific manner. Interventions that address the stress imposed by alignment on the PF compartments may delay PF OA progression and should be developed.

Aged↗