PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Progression”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1978

Scleroderma (progressive systemic sclerosis): progress and course based on a personal series of 118 cases.

A follow-up study has been made of a personal series of 118 cases of patients with scleroderma (progressive systemic sclerosis) followed for periods up to 25 years. These were classified according to the early distribution of skin changes as Type 1 (skin changes in fingers only), 48 cases; Type 2 (skin changes beyond the fingers but mainly in extremities), 47 cases; and Type 3 (diffuse), 19 cases, and atypical, four cases. Eighty per cent of the total series have survived five years, and 68% have survived 10 years. Survival is related to the type of scleroderma, being much better for Types 1 and 2 (acrosclerotic) than for Type 3 (diffuse). Actual compared with expected survival rate was better for younger than for older patients and for females than for males. Although the disease type gives an indication of survival in general, the caution must be used in the individual cases, as the course of the disease is very variable even in patients of the same type, and is subject to remission and relapse.

Adolescent↗
PubMed1979

[Problem of progression in schizophrenia. I. Problem of progression of attack-like forms].

A total of 552 patients with attack-like schizophrenia, who attained old age were examined clinically. It was established that the development of negative changes in such patients occurs predominantly during the first half of life. Subsequently not all patients demonstrate a progressive development of the disease and even if it does occur it is seen in the form of more frequent or longer attacks and a complication of psychopathological disorders. At the same time there is a certain correlation between the clinical picture of the attacks and the severity of deficitary changes. A reverse development of some personality changes in long-term remissions in old age are described.

Adult↗
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–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↗
PubMed2025

A viral clonality evenness score to predict progression to adult T-cell leukaemia in asymptomatic carriers of human T-lymphotropic virus type 1 in Japan: a retrospective longitudinal cohort study.

BACKGROUND: Adult T-cell leukaemia/lymphoma (ATL) is a highly aggressive T-cell malignancy that occurs in approximately 2-7% of individuals with human T-lymphotropic virus type 1 (HTLV-1), after decades of asymptomatic infection. To address the urgent need for predictive biomarkers to identify asymptomatic carriers of HTLV-1 at high risk of progression to ATL, we aimed to evaluate viral clonality sequencing as a potential tool for risk stratification. METHODS: This retrospective longitudinal cohort study involved HTLV-1 carriers enrolled in the Joint Study on Predisposing Factors of ATL Development, a nationwide cohort study initiated in Japan in 2002. Participants were selected from this cohort on the basis of their baseline proviral load at the time of enrolment as an asymptomatic carrier, length of follow-up, and clinical outcome. The cohort was subdivided into three subgroups: the first comprising HTLV-1 carriers who developed ATL, the second comprising carriers with high proviral load (&#x2265;4%) who did not progress to ATL, and the third comprising carriers with low proviral load (<4%) who did not progress to ATL. DNA extracted from peripheral blood mononuclear cells collected at enrolment and at least one follow-up visit was analysed by HTLV-1 clonality sequencing and the proviral load was quantified. We calculated a viral clonality evenness (VCE) score, based on the Shannon Evenness Index, to quantify the uniformity of the clonal distribution of samples, for which 0 represents a perfectly monoclonal architecture and 1 indicates a completely polyclonal landscape. We then estimated the performance of proviral load thresholds and VCE scoring to classify the risk of progression to ATL using the area under the receiver operating characteristic curve (AUC), the accuracy, and Matthews correlation coefficient. VCEs were compared between participant subgroups with the Wilcoxon rank sum test. FINDINGS: 56 participants followed up by JSPFAD between Feb 6, 2003, and July 19, 2022, were included in this study: 17 who progressed to ATL (mean follow-up 8&#xb7;3 years [SD 4&#xb7;0]), 18 who had a high proviral load and did not progress to ATL (9&#xb7;7 years [3&#xb7;4]), and 21 who had a low proviral load and did not progress to ATL (7&#xb7;5 years [3&#xb7;0]). Clonality sequencing of samples from 39 participants who did not progress to ATL revealed hundreds to thousands of HTLV-1 integration sites at both timepoints, corresponding to multiple clones of low and uniform abundance, and these participants had high VCE scores (&#x2265;0&#xb7;694) at baseline. By contrast, most participants (14 of 17) who progressed to ATL had a single predominant clone or two to four predominant clones at both timepoints, and lower VCE scores (<0&#xb7;694) at baseline than those who did not progress (p<0&#xb7;0001). AUCs were very similar for proviral load thresholds (91 [95% CI 80-98]) and VCE scoring (91 [78-100]), although when using methods that give equal weight to every individual, VCE scoring outperformed proviral load thresholds in predicting progression to ATL (accuracy: proviral load 0&#xb7;76 [95% CI 0&#xb7;76-0&#xb7;77], VCE scoring 1&#xb7;00 [0&#xb7;99-1&#xb7;00]; Matthews correlation coefficient: proviral load 0&#xb7;23 [95% CI 0&#xb7;19-0&#xb7;24], VCE scoring 0&#xb7;91 [0&#xb7;80-1&#xb7;00]). Prediction based on VCE scoring indicated no false positives, compared with 20% when using proviral load, although VCE scoring yields a greater number of false negatives (0&#xb7;3% vs 0&#xb7;1%). INTERPRETATION: The implementation of VCE scoring in clinical practice could inform early pre-emptive therapeutic interventions, exclusively targeting individuals with HTLV-1 at high risk and aiming to prevent progression to aggressive, treatment-refractory disease. Further validation, including independent confirmation of the performance of VCE scoring in multiple populations and the characterisation of its temporal dynamics, will be crucial to determine its clinical utility and potential integration into care pathways. FUNDING: Association Jules Bordet, FNRS-T&#xe9;l&#xe9;vie, FCC, WALInnov, FLF, JSPS-KAKENHI, and CoBiA.

Humans↗
PubMed2025

Intracranial and systemic progression on amivantamab in platinum-treated epidermal growth factor receptor exon 20 insertion-mutated advanced non-small cell lung cancer.

BACKGROUND: Amivantamab, an epidermal growth factor receptor (EGFR)-MET bispecific antibody, is approved as monotherapy and as combination therapy for patients with advanced non-small cell lung cancer (NSCLC) harboring various EGFR mutations in first-line and refractory settings. Sites of progressive disease on amivantamab monotherapy are not well understood and could be instructive for treatment management. METHODS: CHRYSALIS (NCT02609776) enrolled participants with NSCLC, including those with treated brain metastases. Brain magnetic resonance imaging was required at screening but performed per local practice after enrollment (conducted postbaseline every 6 [&#xb1;1] weeks after Cycle 1 Day 1). Sites of target, non-target, and new lesion progression were reported. This analysis includes 114 participants with EGFR exon 20 insertion (Ex20ins) NSCLC after disease progression on platinum-based chemotherapy who received amivantamab monotherapy on or before June 4, 2020. RESULTS: As of March 30, 2021, the median follow-up was 12.5&#xa0;months (range, 0.2-30.5). Among 114 participants, the objective response rate by blinded independent central review was 43&#xa0;%; median duration of response was 10.8&#xa0;months, and median progression-free survival was 6.7&#xa0;months. RECIST-defined progressive disease occurred in 72/114 participants (63&#xa0;%); 25/72 (35&#xa0;%) continued amivantamab after progression (4.2 median additional months; range, 1.0-12.5). The most common first sites of progression were the lungs/pleura (29&#xa0;%), followed by bone (21&#xa0;%), brain (15&#xa0;%), and lymph node (12&#xa0;%). Thirteen participants (11&#xa0;%) had intracranial-only first progression. Six of these 13 participants underwent stereotactic radiosurgery (SRS) while continuing amivantamab. The median duration of amivantamab treatment post-progression in these 6 participants was 4.0&#xa0;months (range, 2.3-6.0). SRS was well tolerated, with 2 adverse events reported (nausea and fatigue, n&#xa0;=&#xa0;1 each). CONCLUSIONS: Amivantamab monotherapy in post-platinum Ex20ins NSCLC demonstrated meaningful antitumor activity in participants, and intracranial-only progression was infrequent. Treatment of brain progression with SRS while continuing amivantamab appears feasible and tolerable.

Adult↗
PubMed2026

Transcriptomic profiling across stages of non-muscle-invasive bladder cancer identifies fibroblast activation protein-alpha as a stromal biomarker associated with progression.

BACKGROUND: T1 non-muscle-invasive bladder cancer (NMIBC) represents a biologically aggressive subgroup with substantial heterogeneity in recurrence and progression risk. Current clinicopathological risk stratification tools lack sufficient precision to identify patients at the highest risk of progression to muscle-invasive bladder cancer (MIBC). OBJECTIVE: To characterize transcriptomic differences between T1 and&#x2009;<&#x2009;T1 (Ta/Tis) NMIBC and to explore the association of fibroblast activation protein-&#x3b1; (FAP) gene expression with disease progression. METHODS: Transcriptomic profiling was performed on formalin-fixed paraffin-embedded (FFPE) tumor tissue from 66 patients with primary, treatment-na&#xef;ve NMIBC and 5 patients with T2 disease (included for exploratory comparisons). Analyses included differential gene expression, gene set enrichment analysis (GSEA), molecular subtyping, immune cell deconvolution, and evaluation of FAP expression in relation to recurrence and progression. External validation of FAP was conducted in three independent NMIBC cohorts. RESULTS: T1 tumors demonstrated a distinct transcriptomic profile compared with&#x2009;<&#x2009;T1 tumors, characterized by enrichment of cell cycle-related and metabolic pathways and a higher prevalence of aggressive molecular subtypes. Despite these molecular differences, no statistically significant differences in recurrence-free, progression-free, cancer-specific, and overall survival were observed, likely reflecting limited event numbers. Among recurrent tumors, early recurrences (&#x2264;&#x2009;24&#xa0;months) were associated with epithelial-mesenchymal transition signatures. FAP expression increased with tumor stage (p&#x2009;=&#x2009;0.0005) and was associated with progression (p&#x2009;=&#x2009;0.002) and mortality (p&#x2009;=&#x2009;0.01). Patients with tumors in the highest quartile of FAP expression had worse progression-free survival. This association was consistently observed in three external NMIBC cohorts. CONCLUSIONS: T1 NMIBC exhibits distinct transcriptomic features suggestive of increased biological aggressiveness. Elevated FAP expression is reproducibly associated with progression risk across multiple cohorts, supporting its potential role as a biomarker of aggressive disease. Given the limited number of progression events, these findings should be considered hypothesis-generating and warrant prospective validation before clinical implementation.

Humans↗
PubMed2026

Ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated non-small-cell lung cancer after disease progression on EGFR tyrosine kinase inhibitor therapy (HARMONi): a multicentre, randomised, double-blind, phase 3 trial.

BACKGROUND: Ivonescimab has shown clinical efficacy in non-small-cell lung cancer (NSCLC). We aimed to assess the efficacy and safety of ivonescimab plus chemotherapy versus placebo plus chemotherapy in patients with advanced EGFR-mutated NSCLC whose disease progressed after third-generation EGFR tyrosine kinase inhibitor (TKI) therapy. METHODS: HARMONi is a randomised, placebo-controlled, double-blind, phase 3 trial done at 114 cancer centres and hospitals across Asia, Europe, and North America. Eligible patients were aged at least 18 years (upper limit: 75 years in Asia) with stage IIIB/IIIC or IV non-squamous EGFR-mutated NSCLC, disease progression after treatment with a third-generation EGFR-TKI, and an Eastern Cooperative Oncology Group performance status score of 0 or 1. Patients were randomly assigned (1:1) via a centralised interactive voice response system or interactive web response system to receive ivonescimab (20 mg/kg) or placebo plus pemetrexed (500 mg/m2) and carboplatin (target area under the curve 5 mg/mL per min) intravenously every 3 weeks. Randomisation was stratified by brain metastases status at enrolment and geographical region. The primary endpoints were progression-free survival by blinded independent radiology review committee and overall survival in the intention-to-treat population. Safety was assessed in patients who received at least one dose of trial treatment. This study is registered with ClinicalTrials.gov (NCT06396065), has completed enrolment, and is ongoing for treatment and follow-up. FINDINGS: From Jan 25, 2022, to Oct 1, 2024, 660 individuals were screened for eligibility; of these, 438 were enrolled and randomly assigned to receive ivonescimab plus chemotherapy or placebo plus chemotherapy (219 per group). Of enrolled patients, 257 (59%) were female and 181 (41%) were male; 306 (70%) reported race as Asian, and 105 (24%) as White. At a median follow-up of 22&#xb7;3 months (95% CI 21&#xb7;5-23&#xb7;0), 275 progression or death events had occurred in 345 patients (129 events among 172 patients in the ivonescimab plus chemotherapy group and 146 events among 173 patients in the placebo plus chemotherapy group). Median progression-free survival was 6&#xb7;8 months (95% CI 5&#xb7;7-7&#xb7;1) in the ivonescimab plus chemotherapy group versus 4&#xb7;4 months (4&#xb7;1-5&#xb7;5) in the placebo plus chemotherapy group (hazard ratio [HR] 0&#xb7;52; 95% CI 0&#xb7;41-0&#xb7;66; p<0&#xb7;0001). At a median follow-up of 29&#xb7;7 months (95% CI 27&#xb7;7-31&#xb7;0), 262 deaths occurred in 438 patients (122 in the ivonescimab plus chemotherapy group and 140 in the placebo plus chemotherapy group). Median overall survival was 16&#xb7;8 months (14&#xb7;3-19&#xb7;0) in the ivonescimab plus chemotherapy group versus 14&#xb7;0 months (12&#xb7;8-15&#xb7;7) in the placebo plus chemotherapy group (HR 0&#xb7;79; 0&#xb7;62-1&#xb7;01). The most common grade 3-4 treatment-related adverse events in the ivonescimab plus chemotherapy versus the placebo plus chemotherapy group were decreased neutrophil count (42 [19%] of 218 vs 36 [17%] of 218), decreased white blood cell count (28 [13%] vs 24 [11%]), decreased platelet count (27 [12%] vs 14 [6%]), and anaemia (22 [10%] vs 27 [12%]). Serious treatment-related adverse events occurred in 61 (28%) patients in the ivonescimab plus chemotherapy group and 33 (15%) patients in the placebo plus chemotherapy group. Treatment-related adverse events led to death in four patients (disease progression, multiple organ dysfunction syndrome, and hepatic failure, each in one patient; gastrointestinal haemorrhage and pulmonary embolism in one patient) in the ivonescimab plus chemotherapy group and five patients (pneumonitis, myocardial infarction, cerebrovascular accident, cognitive disorder, and embolic stroke, each in one patient) in the placebo plus chemotherapy group. INTERPRETATION: Ivonescimab plus chemotherapy showed a clinically meaningful and statistically significant progression-free survival benefit in patients with EGFR-mutated NSCLC after progression on EGFR-TKI therapy. The clinical benefit and lack of new safety signals of ivonescimab with chemotherapy support the potential for the combination as a new treatment option in this patient population. FUNDING: Summit Therapeutics.

Humans↗
PubMed2026

Gene polymorphisms associated with progression of primary open-angle glaucoma: A systematic review.

Glaucoma is the leading global cause of irreversible blindness, with primary open-angle glaucoma (POAG) its most prevalent subtype. While elevated intraocular pressure is a major risk factor, glaucoma progression is multifactorial, influenced by genetic, environmental, vascular and mechanical factors. Genetic polymorphisms have been linked to both POAG susceptibility and progression, yet most studies focus on risk factors for disease onset rather than progression. We provide an overview of the current literature on gene polymorphisms associated with POAG progression. We conducted a systematic search following PRISMA guidelines in MEDLINE, EMBASE, Web of Science, Cochrane Library, Scopus and Public Health Genomics and Precision Health Knowledge Base. Eligible studies investigated associations between genetic variants and structural or functional markers of glaucoma progression in adult-onset POAG patients. Eighteen articles were included. HLA class I haplotypes (A1-B8 and A2-B40) and MYOC.mt1+ carriers showed faster progression of optic nerve head damage. The APOE &#x3b5;4 allele was linked to faster macular thinning in normal tension glaucoma patients. BDNF rs6265 Val/Val homozygotes exhibited accelerated retinal nerve fiber layer loss, particularly in females. TGFBR3-CDC7 (rs1192415: G) and MYOC.mt1+ carriers experienced accelerated visual field deterioration. Carriers of GAS7 (rs9913911: AA), IL1B (rs1143627: CT and rs16944: CT) and OPTN (rs2234968) had a higher likelihood of requiring surgery. Variants in ABCA1, CDKN2B-AS, eNOS and Piezo1 showed inconclusive results. These findings support a role for genetic polymorphisms in POAG progression and highlight the potential of genetic screening to identify patients at increased risk for rapid disease progression.

Disease progression↗
PubMed1979

Psychological correlates of progression of atherosclerosis in men.

Patients who underwent repetitive repetitive coronary angiograms at an average interval of 17 months completed the Jenkins Activity Survey (n = 66) and were given the Rosenman diagnostic interview to measure Type A behavior (n = 45). Significant progression of coronary artery disease was judged to be an increase in occlusion of 25% or more, or progression to total occlusion in any vessel. At subsequent study, 30% of the patients showed evidence of progression. Progression was much more likely in patients with initially more severe disease and was marginally related to cigarette smoking when initial level of disease was controlled. Interview assessment of Type A did not discriminate reliably between the groups in the smaller sample of patients given this measure. There was significant positive association between magnitude of Activity Survey Type A scores and progression of disease, although mean scores on the Type A scale were not reliably different between the Progression and No Progression groups. The pattern of results suggested that extreme Type B subjects (classified by Activity Survey) were unlikely to show progression over this time period.

Adult↗
PubMed2026

Genetic Associations with Temporal Modeling of Alzheimer's Disease Progression Supports a Novel Paradigm for Disease Risk.

A major challenge in Alzheimer's disease (AD) research is predicting who will develop AD, how it progresses, and how to slow, prevent, or reverse progression. Here, we apply a data-driven timeline inference framework to sparse longitudinal blood metabolomics data to reconstruct AD timelines and derive individual-specific timeline progression rates. Inferred temporal locations for each metabolomics sample along the AD timeline closely track clinical severity, while timeline progression rates capture inter-individual differences in the speed of pathophysiological progression. Genome-wide association studies of timeline progression rate identify novel loci distinct from those in AD case-control studies, notably showing no effect of the major risk locus APOE. These findings support a multidimensional paradigm of AD risk in which disease potential and progression act as partially independent factors. By explicitly modeling disease dynamics, this work reveals genetic contributions not captured by traditional approaches and provides a framework for studying AD and other progressive disorders.

Journal Article↗
PubMed2026

Longitudinal progression, metrics, age-dependence, and modifiers of ataxia severity in SCA27B: a multicentre study of 219 patients.

BACKGROUND: Spinocerebellar Ataxia 27B (SCA27B) is a novel, frequent and likely treatable late-onset autosomal-dominant ataxia caused by GAA repeat-expansions in FGF14. For understanding disease evolution and imminent trial planning, metrics of the most widely used clinical outcome assessment (Scale for the Assessment and Rating of Ataxia/SARA), longitudinal progression and modifiers thereof are warranted. METHODS: Multicentre intercontinental observational study (2015-2024) of 661 assessments from 219 patients with SCA27B (age: 68 &#xb1; 10 years; SARA: 9 &#xb1; 6 points) with item-level distribution-based analyses to characterise SARA metrics relative to ageing-related impairment in 390 healthy controls; and linear mixed-effects modelling to determine longitudinal progression and demographic or genetic modifiers. FINDINGS: Ataxia severity in SCA27B as assessed by SARA was primarily attributable to gait, stance, and lower-limb impairment; other ataxia domains scored &#x2264;1 SARA point in 79-94% of patients. Discrimination of SCA27B motor performance from controls decreased with age due to ageing-related motor variability captured by SARA, thus limiting potential metric response windows for symptomatic treatments. Disease progression was faster in the presence of interfering ageing-related comorbidities in 14 (6%) patients. Overall longitudinal progression of SCA27B was 0.54 SARA points/year [95% CI: 0.37-0.71]. Expansions of (GAA)> 180 repeats were frequent also on the shorter allele (n = 18 (8%), range: 196-348 repeats), and associated with faster progression (+1.6 SARA points/year, [95% CI: 0.9-2.2]), including also otherwise less affected ataxia domains speech and sitting. INTERPRETATION: Disease progression in SCA27B is characterised by mild progression, ageing-related motor variabilities and comorbidities, and associated with repeat size on both alleles. FUNDING: Else-Kr&#xf6;ner-Fresenius-Stiftung, EU, DFG, BMBF, CIHR, NAF, Ataxia-UK, CSC.

Humans↗