Assessment of the usefulness of prognostic Van Nuys Prognostic Index in the treatment in ductal carcinoma in situ in 15-year observation
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SUBMITTER: Kunkiel M
PROVIDER: S-EPMC8608918 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Multiple invasive foci has been shown to increase the risk of lymph node metastasis (LNM) in early breast cancer, but its prognostic implication remains unknown. We aimed to identify the prognostic value of the number of invasive foci in ductal carcinoma in situ with minimal invasion of the breast (DCIS-MI), and further establish a prognostic invasive lesion index (ILI). A total of 193 patients with DCIS-MI (the invasive component was up to 10 mm in diameter) were included. Univariate and multivariate analysis (logistic regression) were used to evaluate the predictive value of the number of invasive foci in LNM. The Kaplan-Meier curve was used for survival analysis. More than five invasive foci was an independent predictor for LNM (OR, 2.67, 95% CI, 1.12-6.33, P = 0.026), and associated with significantly shorter disease-free survival (DFS) and overall survival (OS) compared with no more than five invasive foci (mean DFS 123.8 vs. 148.0 months, P = 0.002; and mean OS 133.5 vs. 151.4 months, P = 0.025). The ILI was established by the sum scores of the number of invasive foci and the invasive component size, having an optimal cut-off point of 5.5 scores. The high-ILI group (ILI >5 scores) had a higher incidence of LNM (23.6% vs. 6.9%) and worse prognosis than the low-ILI group (ILI ≤5 scores). In conclusion, more than five invasive foci was an independent predictor for LNM and an unfavorable prognostic parameter. The ILI could potentially be used to predict survival prognosis in patients with DCIS-MI.
| S-EPMC5673919 | biostudies-literature
Project description:Background/objectivesPrognostic indices rarely include cognition. We determined if a comprehensive cognitive screen or brief individual items were associated with improved mortality predictions of a widely used prognostic index.Design, setting, and participantsThe National Social Life Health and Aging Project Wave 2, a nationally representative, cross-sectional, in-home survey conducted in 2010 to 2011 on 3,199 community-dwelling adults aged 60 to 99 years.MeasurementsCognition was measured using a Survey-Adapted Montreal Cognitive Assessment (MoCA-SA) grouped into three screened categories: screen normal (≥24 points), screen positive for mild cognitive impairment (18-23 points), and screen positive for dementia (<18 points). Single-item cognitive measures included clock-draw and five-word delayed recall. We constructed a modified Lee Prognostic Index (range = 0-18 points) based on age, behavior, function, and comorbidities shown to predict long-term mortality. We used logistic regression and the fraction of new information provided to determine if each cognitive measure improved the Lee index's 5-year mortality prediction.ResultsThe sample was 54% female and had a mean age of 72 years, MoCA-SA score of 22 (SD = 4.5), and Lee index of 7 (SD = 3). Regression analysis indicated the MoCA-SA modestly improved the Lee index's mortality prediction (P < .001; fraction of new information provided = 0.06); for low Lee index scores (<4 points), the absolute mortality rate difference was 7% by cognitive status; and for higher Lee index scores (4-7 points or 8-12 points), the absolute mortality rate difference was 15% by cognitive status. The clock-draw and delayed-recall items added similar value to mortality predictions as the longer MoCA-SA. Cognition had the third highest fraction of new information of all 13 Lee index items.ConclusionIncorporating a brief measure of cognition into a modified Lee index, even with single items, resulted in more accurate 5-year mortality risk predictions. Cognition should be included in prognostic calculators in older adults given its independent association with mortality risk. J Am Geriatr Soc 68:1796-1802, 2020.
| S-EPMC8189656 | biostudies-literature
Project description:Ductal carcinoma in situ (DCIS) is considered a non-obligatory precursor for invasive ductal carcinoma (IDC). Around 70% of women with atypical ductal hyperplasia (ADH) undergo unnecessary surgery due to the difficulty in differentiating ADH from low-grade DCIS. If untreated, 14-60% of DCIS progress to IDC, highlighting the importance of identifying a DCIS gene signature. Human transcriptome data of breast tissue samples representing each step of BC progression were analyzed and high expression of carboxypeptidase B1 (CPB1) expression strongly correlated with DCIS. This was confirmed by quantitative PCR in breast tissue samples and cell lines model. High CPB1 expression correlated with better survival outcome, and mRNA level was highest in DCIS than DCIS adjacent to IDC and IDC. Moreover, loss of CPB1 in a DCIS cell line led to invasive properties associated with activation of HIF1α, FN1, STAT3 and SPP1 and downregulation of SFRP1 and OS9. The expression of CPB1 could predict 90.1% of DCIS in a cohort consisting of DCIS and IDC. We identified CPB1, a biomarker that helps differentiate DCIS from ADH or IDC and in predicting if a DCIS is likely to progress to IDC, thereby helping clinicians in their decisions.
| S-EPMC8038727 | biostudies-literature
Project description:BackgroundThe role of different subtypes of tumour infiltrating lymphocytes (TILs) in breast ductal carcinoma in situ (DCIS) is still poorly defined. This study aimed to assess the prognostic significance of B and T lymphocytes and immune checkpoint proteins expression in DCIS.MethodsA well characterised DCIS cohort (n = 700) with long-term follow-up comprising pure DCIS (n = 508) and DCIS mixed with invasive carcinoma (IBC; n = 192) were stained immunohistochemically for CD20, CD3, CD4, CD8, FOXP3, PD1 and PDL1. Copy number variation and TP53 mutation status were assessed in a subset of cases (n = 58).ResultsCD3+ lymphocytes were the predominant cell subtype in the pure DCIS cohort, while FOXP3 showed the lowest levels. PDL1 expression was mainly seen in the stromal TILs. Higher abundance of TILs subtypes was associated with higher tumour grade, hormone receptor negativity and HER2 positivity. Mutant TP53 variants were associated with higher levels of stromal CD3+, CD4+ and FOXP3+ cells. DCIS coexisting with invasive carcinoma harboured denser stromal infiltrates of all immune cells and checkpoint proteins apart from CD4+ cells. Stromal PD1 was the most differentially expressed protein between DCIS and invasive carcinoma (Z = 5.8, p < 0.0001). Dense TILs, stromal FOXP3 and PDL1 were poor prognostic factors for DCIS recurrence, while dense TILs were independently associated with poor outcome for all recurrences (HR = 7.0; p = 0.024), and invasive recurrence (HR = 2.1; p = 0.029).ConclusionsImmunosuppressive proteins are potential markers for high risk DCIS and disease progression. Different stromal and intratumoural lymphocyte composition between pure DCIS, DCIS associated with IBC and invasive carcinoma play a potential role in their prognostic significance and related to the underlying genomic instability. Assessment of overall TILs provides a promising tool for evaluation of the DCIS immune microenvironment.
| S-EPMC7217899 | biostudies-literature
Project description:BackgroundPancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by complex biological features and poor prognosis. A prognostic stratification of PDAC would help to improve patient management. The aim of this study was to analyse the expression of Ki-67 in relation to prognosis in a cohort of patients with PDAC who had surgical treatment.MethodsPatients who had pancreatic resection between August 2010 and October 2014 for PDAC at two Italian centres were reviewed retrospectively. Patients with metastatic or locally advanced disease, those who received neoadjuvant chemotherapy, patients with PDAC arising from intraductal papillary mucinous neoplasm and those with missing data were excluded. Clinical and pathological data were retrieved and analysed. Ki-67 expression was evaluated using immunohistochemistry and patients were stratified into three subgroups. Survival analyses were performed for disease-free (DFS) and disease-specific (DSS) survival outcomes according to Ki-67 expression and tumour grading.ResultsA total of 170 patients met the selection criteria. Ki-67 expression of 10 per cent or less, 11-50 per cent and more than 50 per cent significantly correlated with DFS and DSS outcomes (P = 0·016 and P = 0·002 respectively). Ki-67 index was an independent predictor of poor DFS (hazard ratio (HR) 0·52, 95 per cent c.i. 0·29 to 0·91; P = 0·022) and DSS (HR 0·53, 0·31 to 0·91; P = 0·022). Moreover, Ki-67 index correlated strongly with tumour grade (P < 0·001). Patients with PDAC classified as a G3 tumour with a Ki-67 index above 50 per cent had poor survival outcomes compared with other patients (P < 0·001 for both DFS and DSS).ConclusionKi-67 index could be of use in predicting the survival of patients with PDAC. Further investigation in larger cohorts is needed to validate these results.
| S-EPMC6773637 | biostudies-literature
Project description:Abstract Aim Cachexia is associated with the morbidity and mortality of cancer patients. The cachexia index (CXI) is a novel biomarker of cachexia associated with the prognosis for certain cancers. This study analyzed the relationship between CXI with long‐term outcomes of gastric cancer patients. Methods We included 175 gastric cancer patients who underwent curative gastrectomy at our hospital between January 2011 and October 2019. The CXI was calculated using skeletal muscle index, serum albumin level, and neutrophil‐to‐lymphocyte ratio. The prognostic value of CXI was investigated by univariate and multivariate Cox hazard regression models adjusting for potential confounders. Results In the multivariate analyses, tumor location (hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.11–0.49; p < 0.01), disease stage (HR, 15.4; 95% CI, 4.18–56.1; p < 0.01), and low CXI (HR, 2.97; 95% CI, 1.01–8.15; p = 0.03) were independent and significant predictors of disease‐free survival. Disease stage (HR, 9.88; 95% CI, 3.53–29.1; p < 0.01) and low CXI (HR, 4.07; 95% CI, 1.35–12.3; p < 0.01) were independent and significant predictors of overall survival. The low CXI group had a lower body mass index (p = 0.02), advanced disease stage (p = 0.034), and a lower prognostic nutritional index (p < 0.01). Conclusions Cachexia index is associated with a poor prognosis for gastric cancer, suggesting the utility of comprehensive assessment using nutritional, physical, and inflammatory status. Cachexia index, a recently defined parameter can be a prognostic predictor for gastric cancer patients. Our results suggest that inflammatory status and muscle mass are associated with tumor recurrence and progression in gastric cancer.
| S-EPMC10472360 | biostudies-literature
Project description:ObjectiveEducational, and audit and feedback interventions are effective in promoting health professional behaviour change and evidence adoption. However, we lack evidence to pinpoint which particular features make them most effective. Our objective is to identify determinants of quality in professional behaviour change interventions, as perceived by participants.DesignWe performed a comparative observational study using data from the Veterans' Medicines Advice and Therapeutics Education Services program, a nation-wide Australian Government Department of Veterans' Affairs funded program that provides medicines advice and promotes physician adoption of best practices by use of a multifaceted intervention (educational material and a feedback document containing individual patient information).SettingPrimary care practices providing care to Australian veterans.ParticipantsGeneral practitioners (GPs) targeted by 51 distinct behaviour change interventions, implemented between November 2004 and June 2018.Primary and secondary outcome measuresWe extracted features related to presentation (number of images, tables and characters), content (polarity and subjectivity using sentiment analysis, number of external links and medicine mentions) and the use of five behaviour change techniques (prompt/cues, goal setting, discrepancy between current behaviour and goal, information about health consequences, feedback on behaviour). The main outcome was perceived usefulness, extracted from postintervention survey.ResultsOn average, each intervention was delivered to 9667 GPs. Prompt and goal setting strategies in the audit and feedback were independently correlated to perceived usefulness (p=0.030 and p=0.005, respectively). The number of distinct behaviour change techniques in the audit and feedback was correlated with improved usefulness (Pearson's coefficient 0.45 (0.19, 0.65), p=0.001). No presentation or content features in the educational material were correlated with perceived usefulness.ConclusionsThe finding provides additional evidence encouraging the use of behaviour change techniques, in particular prompt and goal setting, in audit and feedback interventions.
| S-EPMC7559049 | biostudies-literature
Project description:Following the implementation of breast screening programs, the occurrence of ductal carcinoma in situ (DCIS) as an early type of neoplasia has increased. Although the prognosis is promising, 20%-50% of DCIS patients will progress to invasive ductal carcinoma (IDC) if not treated. It is essential to look for promising biomarkers for predicting DCIS prognosis. The Gene Expression Omnibus (GEO) database was used to explore the expression of genes that differed between DCIS and normal tissue in this investigation. Enrichment analysis was performed to characterize the biological role and intrinsic process pathway. The Cancer Genome Atlas Breast Cancer Dataset was used to categorize the hub genes, and the results were confirmed using the Cytoscape plugin CytoHubba and MCODE. The prognostic ability of the core gene signature was determined through time-dependent receiver operating characteristic (ROC), Kaplan-Meier survival curve, Oncomine databases, and UALCAN databases. In addition, the prognostic value of core genes was verified in proliferation assays. We identified 217 common differentially expressed genes (DEGs) in the present study, with 101 upregulated and 138 downregulated genes. The top genes were obtained from the PPI network (protein-protein interaction). A unique six-gene signature (containing GAPDH, CDH2, BIRC5, NEK2, IDH2, and MELK) was developed for DCIS prognostic prediction. Centered on the Cancer Genome Atlas (TCGA) cohort, the ROC curve showed strong results in prognosis prediction. The six core gene signatures is often overexpressed in DCIS, with a weak prognosis. Furthermore, when breast cancer cells are transfected with small interfering RNAs, downregulation of core gene expression substantially inhibits cell proliferation, revealing a high potential for employing core genes in DCIS prognosis. In conclusion, the current investigation verified the six core genes signatures for prospective DCIS biomarkers, which may aid clinical decision-making for individual care.
| S-EPMC9939111 | biostudies-literature
Project description:PurposeThe Radiation Therapy Oncology Group 9804 study identified good-risk patients with ductal carcinoma in situ (DCIS), a breast cancer diagnosis found frequently in mammographically detected cancers, to test the benefit of radiotherapy (RT) after breast-conserving surgery compared with observation.Patients and methodsThis prospective randomized trial (1998 to 2006) in women with mammographically detected low- or intermediate-grade DCIS, measuring less than 2.5 cm with margins ≥ 3 mm, compared RT with observation after surgery. The study was designed for 1,790 patients but was closed early because of lower than projected accrual. Six hundred thirty-six patients from the United States and Canada were entered; tamoxifen use (62%) was optional. Ipsilateral local failure (LF) was the primary end point; LF and contralateral failure were estimated using cumulative incidence, and overall and disease-free survival were estimated using the Kaplan-Meier method.ResultsMedian follow-up time was 7.17 years (range, 0.01 to 11.33 years). Two LFs occurred in the RT arm, and 19 occurred in the observation arm. At 7 years, the LF rate was 0.9% (95% CI, 0.0% to 2.2%) in the RT arm versus 6.7% (95% CI, 3.2% to 9.6%) in the observation arm (hazard ratio, 0.11; 95% CI, 0.03 to 0.47; P < .001). Grade 1 to 2 acute toxicities occurred in 30% and 76% of patients in the observation and RT arms, respectively; grade 3 or 4 toxicities occurred in 4.0% and 4.2% of patients, respectively. Late RT toxicity was grade 1 in 30%, grade 2 in 4.6%, and grade 3 in 0.7% of patients.ConclusionIn this good-risk subset of patients with DCIS, with a median follow-up of 7 years, the LF rate was low with observation but was decreased significantly with the addition of RT. Longer follow-up is planned because the timeline for LF in this setting seems protracted.
| S-EPMC4334775 | biostudies-literature
Project description:BackgroundImpaired DNA repair mechanism is one of the cancer hallmarks. Flap Endonuclease 1 (FEN1) is essential for genomic integrity. FEN1 has key roles during base excision repair (BER) and replication. We hypothesised a role for FEN1 in breast cancer pathogenesis. This study aims to assess the role of FEN1 in breast ductal carcinoma in situ (DCIS).MethodsExpression of FEN1 protein was evaluated in a large (n = 1015) well-characterised cohort of DCIS, comprising pure (n = 776) and mixed (DCIS coexists with invasive breast cancer (IBC); n = 239) using immunohistochemistry (IHC).ResultsFEN1 high expression in DCIS was associated with aggressive and high-risk features including higher nuclear grade, larger tumour size, comedo type necrosis, hormonal receptors negativity, higher proliferation index and triple-negative phenotype. DCIS coexisting with invasive BC showed higher FEN1 nuclear expression compared to normal breast tissue and pure DCIS but revealed significantly lower expression when compared to the invasive component. However, FEN1 protein expression in DCIS was not an independent predictor of local recurrence-free interval.ConclusionHigh FEN1 expression is linked to features of aggressive tumour behaviour and may play a role in the direct progression of DCIS to invasive disease. Further studies are warranted to evaluate its mechanistic roles in DCIS progression and prognosis.
| S-EPMC8233293 | biostudies-literature