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Targeted Oncology Nov 2023Delta-like ligand 3 (DLL3), a member of the Notch pathway, has been identified as a potential therapeutic target as it is highly expressed in small cell lung cancer...
BACKGROUND
Delta-like ligand 3 (DLL3), a member of the Notch pathway, has been identified as a potential therapeutic target as it is highly expressed in small cell lung cancer (SCLC), a subtype accounting for 15% of lung cancer cases.
OBJECTIVE
A systematic literature review (SLR) was conducted to understand the prevalence and prognostic impact of DLL3 expression on survival of patients with SCLC and treatment response.
PATIENTS AND METHODS
Systematic literature searches were conducted across multiple databases to capture studies of any SCLC population that evaluated DLL3 expression. Specific outcomes of interest included prevalence of DLL3 expression, method of expression analysis, and impact on outcome, including treatment response and survival (overall, progression-free, disease-free) according to varying levels of DLL3 expression/positivity. Standard risk of bias tools were used to evaluate study quality.
RESULTS
Among the 30 included studies, the most common DLL3 testing method was immunohistochemistry (N = 26, 86.7%). For comparability, results focused on the 13 (22.3%) studies that used the Ventana DLL3 (SP347) immunohistochemistry assay. The prevalence of DLL3 positivity ranged from 80.0-93.5% for studies using a threshold of ≥ 1% of tumor cells (N = 4) and 58.3-91.1% for studies with a ≥ 25% threshold (N = 4). DLL3 expression was generally categorized as high using cutoffs of ≥ 50% (prevalence range: 45.8-79.5%; N = 6) or ≥ 75% (prevalence range: 47.3-75.6%; N = 5) of cells with positivity. Two studies used an H-score of ≥ 150 to define high DLL3 expression with prevalence ranging from 33.3-53.1%. No consistent associations were seen between DLL3 expression level and patient age, sex, smoking history, or disease stage. Two studies reported change in DLL3 expression category (high versus low) before and after chemotherapy. No statistically significant differences were reported between DLL3 expression groups and survival (overall, progression-free, or disease-free) or treatment response.
CONCLUSIONS
There is a high prevalence of DLL3 expression in SCLC. Further research and analytical methods may help to characterize different populations of patients with SCLC based on DLL3 expression. While no significant prognostic factor in the included studies was identified, additional cohort studies using standardized methodology, with longer follow-up, are needed to better characterize any potential differences in patient survival or response by DLL3 expression level in SCLC.
Topics: Humans; Small Cell Lung Carcinoma; Lung Neoplasms; Prognosis; Ligands; Prevalence; Membrane Proteins; Intracellular Signaling Peptides and Proteins
PubMed: 37930513
DOI: 10.1007/s11523-023-01008-x -
Reviews in Endocrine & Metabolic... Dec 2023Inflammation has been associated with tumor development and circulating inflammatory biomarkers have been proposed as possible predictors of recurrence of several solid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Inflammation has been associated with tumor development and circulating inflammatory biomarkers have been proposed as possible predictors of recurrence of several solid tumors. However, the role of inflammation markers in differentiated thyroid carcinoma (DTC) is still uncertain.
OBJECTIVE
This meta-analysis aimed to assess the prognostic value of neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and platelet-to-lymphocyte ratio (PLR) in patients with DTC.
METHODS
Studies investigating the association between survival and preoperative circulating inflammatory markers in DTC patients were included. The primary outcome was disease-free survival (DFS). Cumulative logarithms of the hazard ratio (log-HRs) with 95% CI were calculated through the inverse variance method using a random-effects model.
RESULTS
A total of 7599 patients with a mean age of 48.89 (95% CI 44.16-53.63) were included. The estimated pooled log-HRs for DFS were 0.07 for NLR (95% CI -0.12-0.26; p = 0.43), -0.58 for LMR (95% CI -1.21-0.05; p = 0.06), and 0.01 (95% CI 0-0.01; p = 0.21) for PLR.
CONCLUSIONS
Our meta-analysis showed no association between NLR, PLR, LMR and DFS in DTC; however, more prospective data are needed to better define the association between inflammatory status and prognosis of DTC.
Topics: Humans; Middle Aged; Prognosis; Prospective Studies; Lymphocytes; Inflammation; Thyroid Neoplasms
PubMed: 37828383
DOI: 10.1007/s11154-023-09845-x -
Anticancer Research Oct 2023Low human epidermal growth factor receptor 2 expression (HER2-low: 1+/2+ by immunohistochemistry without HER2 amplification) is emerging as defining a specific breast... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND/AIM
Low human epidermal growth factor receptor 2 expression (HER2-low: 1+/2+ by immunohistochemistry without HER2 amplification) is emerging as defining a specific breast cancer (BC) subgroup owing to its distinct biological features. However, its prognostic role has not been confirmed in clinical practice. We conducted a systematic review and meta-analysis to determine the prognostic role of HER2-low status in patients with estrogen receptor-positive (ER+) early BC.
MATERIALS AND METHODS
We searched PubMed, EMBASE, and the Cochrane Library for prospective or retrospective studies that reported data on overall (OS) or disease-free (DFS) survival for HER2-low compared to HER2-negative BC. Data were pooled using hazard ratios (HR) with confidence intervals (CI) for OS/DFS of HER2-low vs. HER2-negative subgroups according to the random-effects model. OS was the primary outcome measure, and DFS and pathological complete response were the secondary endpoints.
RESULTS
An analysis was made of 25 studies collected, including 34,965 patients with HER2-low BC. A HER2-low status was associated with an HR for OS of 0.83 (95% CI=0.76-0.9, p<0.0.01). Similarly, a pooled HR of 0.89 (95% CI=0.840.94, p<0.0.01) showed that patients with HER2-low BC had an increased DFS. Pathological complete response was significantly lower in HER2-low BC in 13 studies (OR=0.72, 95% CI=0.58-0.91; p<0.01).
CONCLUSION
Based on these data, HER2-low status should be identified as a potential prognostic factor in early stage ER+ BC. This should be taken into account when considering treatment in (neo)adjuvant settings, and it should be a potential stratification factor in future investigations.
Topics: Humans; Female; Breast Neoplasms; Prognosis; Retrospective Studies; Prospective Studies; Receptor, ErbB-2; Proportional Hazards Models; Disease-Free Survival
PubMed: 37772569
DOI: 10.21873/anticanres.16625 -
ESMO Open Aug 2023Human epidermal growth factor receptor 2 (HER2)-low expression in breast cancer has been recently identified as a new therapeutic target. However, it is unclear if... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Human epidermal growth factor receptor 2 (HER2)-low expression in breast cancer has been recently identified as a new therapeutic target. However, it is unclear if HER2-low status has an independent impact on prognosis.
MATERIALS AND METHODS
A systematic literature research was carried out to identify studies comparing survival outcomes of patients affected by HER2-low versus HER2-zero breast cancer. Using random-effects models, pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated for progression-free survival (PFS) and overall survival (OS) in the metastatic setting as well as disease-free survival (DFS), OS and pathological complete response (pCR) in the early setting. Subgroup analyses by hormone receptor (HoR) status were carried out. The study protocol is registered on PROSPERO (n.CRD42023390777).
RESULTS
Among 1916 identified records, 42 studies including 1 797 175 patients were eligible. In the early setting, HER2-low status was associated with significant improved DFS (HR 0.86, 95% CI 0.79-0.92, P < 0.001) and OS (HR 0.90, 95% CI 0.85-0.95, P < 0.001) when compared to HER2-zero status. Improved OS was observed for both HoR-positive and HoR-negative HER2-low populations, while DFS improvement was observed only in the HoR-positive subgroup. HER2-low status was significantly associated with a lower rate of pCR as compared to HER2-zero status both in the overall population (OR 0.74, 95% CI 0.62-0.88, P = 0.001) and in the HoR-positive subgroup (OR 0.77, 95% CI 0.65-0.90, P = 0.001). In the metastatic setting, patients with HER2-low breast cancers showed better OS when compared with those with HER2-zero tumours in the overall population (HR 0.94, 95% CI 0.89-0.98, P = 0.008), regardless of HoR status. No significant PFS differences were found.
CONCLUSIONS
Compared with HER2-zero status, HER2-low status appears to be associated with a slightly increased OS both in the advanced and early settings, regardless of HoR expression. In the early setting, HER2-low tumours seem to be associated to lower pCR rates, especially if HoR-positive.
Topics: Humans; Female; Breast Neoplasms; Prognosis; Disease-Free Survival; Progression-Free Survival; Proportional Hazards Models
PubMed: 37413762
DOI: 10.1016/j.esmoop.2023.101592 -
Medicina (Kaunas, Lithuania) Jan 2023: Postoperative pancreatic fistula (POPF) is one of the most challenging complications after pancreatic resections, associated with prolonged hospital stay and high... (Review)
Review
: Postoperative pancreatic fistula (POPF) is one of the most challenging complications after pancreatic resections, associated with prolonged hospital stay and high mortality. Early identification of pancreatic fistula is necessary for the treatment to be effective. Several prognostic factors have been identified, although it is unclear which one is the most crucial. Some studies show that post-pancreatectomy hypophosphatemia may be associated with the development of POPF. The aim of this systematic review was to determine whether postoperative hypophosphatemia can be used as a prognostic factor for postoperative pancreatic fistula. : The systematic literature review was performed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations (PRISMA) and was registered in the International Prospective Register of Systematic Reviews (PROSPERO). The PubMed, ScienceDirect, and Web of Science databases were systematically searched up to the 31st of January 2022 for studies analyzing postoperative hypophosphatemia as a prognostic factor for POPF. Data including study characteristics, patient characteristics, operation type, definitions of postoperative hypophosphatemia and postoperative pancreatic fistula were extracted. : Initially, 149 articles were retrieved. After screening and final assessment, 3 retrospective studies with 2893 patients were included in this review. An association between postoperative hypophosphatemia and POPF was found in all included studies. Patients undergoing distal pancreatectomy were more likely to develop severe hypophosphatemia compared to patients undergoing proximal pancreatectomy. Serum phosphate levels on postoperative day 4 (POD 4) and postoperative day 5 (POD 5) remained significantly lower in patients who developed leak-related complications showing a slower recovery of hypophosphatemia from postoperative day 3 (POD 3) through postoperative day 7 (POD 7). Moreover, body mass index (BMI) higher than 30 kg/m, soft pancreatic tissue, abnormal white blood cell count on postoperative day 3 (POD 3), and shorter surgery time were associated with leak-related complications (LRC) and lower phosphate levels. : Early postoperative hypophosphatemia might be used as a prognostic biomarker for early identification of postoperative pancreatic fistula. However, more studies are needed to better identify significant cut-off levels of postoperative hypophosphatemia and development of hypophosphatemia in the postoperative period.
Topics: Humans; Pancreatic Fistula; Prognosis; Retrospective Studies; Hypophosphatemia; Postoperative Complications; Phosphates; Postoperative Period; Risk Factors
PubMed: 36837475
DOI: 10.3390/medicina59020274 -
International Journal of Molecular... Jul 2023The aim of this systematic review and meta-analysis was to evaluate the current evidence in relation to the clinicopathological and prognostic significance of epidermal... (Meta-Analysis)
Meta-Analysis
Prognostic and Clinicopathological Significance of Epidermal Growth Factor Receptor (EGFR) Expression in Oral Squamous Cell Carcinoma: Systematic Review and Meta-Analysis.
The aim of this systematic review and meta-analysis was to evaluate the current evidence in relation to the clinicopathological and prognostic significance of epidermal growth factor receptor (EGFR) overexpression in patients with oral squamous cell carcinoma (OSCC). We searched MEDLINE/PubMed, Embase, Web of Science, and Scopus for studies published before November 2022. We evaluated the quality of primary-level studies using the QUIPS tool, conducted meta-analyses, examined inter-study heterogeneity via subgroup analyses and meta-regressions, and performed small-study effects analyses. Fifty primary-level studies (4631 patients) met the inclusion criteria. EGFR overexpression was significantly associated with poor overall survival (hazard ratio [HR] = 1.38, 95% confidence intervals [CI] = 1.06-1.79, = 0.02), N+ status (odds ratio [OR] = 1.37, 95%CI = 1.01-1.86, = 0.04), and moderately-poorly differentiated OSCC (OR = 1.43, 95% CI = 1.05-1.94, = 0.02). In addition, better results were obtained by the application of a cutoff point ≥10% tumor cells with EGFR overexpression ( < 0.001). In conclusion, our systematic review and meta-analysis supports that the immunohistochemical assessment of EGFR overexpression may be useful as a prognostic biomarker for OSCC.
Topics: Humans; Carcinoma, Squamous Cell; Mouth Neoplasms; Squamous Cell Carcinoma of Head and Neck; Prognosis; ErbB Receptors; Head and Neck Neoplasms; Biomarkers, Tumor
PubMed: 37569265
DOI: 10.3390/ijms241511888 -
The Journal of Urology Oct 2021Sarcopenia, an age-related loss of muscle mass and function, may predict adverse outcomes for patients with urological cancers. However, the clinical implications and...
PURPOSE
Sarcopenia, an age-related loss of muscle mass and function, may predict adverse outcomes for patients with urological cancers. However, the clinical implications and significance of sarcopenic obesity are not well understood. We systematically reviewed data on the prevalence and prognostic impact of sarcopenic obesity for patients with renal cell carcinoma, urothelial carcinoma and prostate cancer undergoing treatment.
MATERIALS AND METHODS
We searched EMBASE®, PubMed®/MEDLINE® and Scopus® for relevant original articles and abstracts published between January 2010 and February 2021. Primary outcomes were overall survival (OS), cancer-specific survival (CSS) and progression-free survival. The secondary outcome was the prevalence of sarcopenic obesity.
RESULTS
A total of 15 studies comprising 3,866 patients were included. Of the 10 studies that evaluated survival outcomes, the association between sarcopenic obesity and survival was mixed. One of 10 studies showed a significant association of sarcopenic obesity with OS (HR 0.7, 95% CI 0.51-0.98; p=0.04). One additional study showed reported a trend for shorter OS (p=0.05) associated with sarcopenic obesity. Others reported that it is an adverse prognostic factor for CSS (HR 5.0, 95% CI 1.4-16.7; p=0.01). All other studies did not demonstrate that sarcopenic obesity was of prognostic relevance with regard to OS, CSS and progression-free survival. Overall, its mean prevalence was 27% (range 11-63).
CONCLUSIONS
There is considerable heterogeneity in methods used to define sarcopenic obesity in the literature, and current data are limited. Future studies are needed to further understand the relationship of obesity and sarcopenia on the clinical trajectory of patients with urological cancer.
Topics: Body Composition; Comorbidity; Humans; Obesity; Prevalence; Prognosis; Progression-Free Survival; Risk Assessment; Risk Factors; Sarcopenia; Urologic Neoplasms
PubMed: 34032495
DOI: 10.1097/JU.0000000000001873 -
PeerJ 2023The receptor for activated C kinase 1 (RACK1) expression is associated with clinicopathological characteristics and the prognosis of various cancers; however, the... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The receptor for activated C kinase 1 (RACK1) expression is associated with clinicopathological characteristics and the prognosis of various cancers; however, the conclusions are controversial. As a result, this study aimed to explore the clinicopathological and prognostic values of RACK1 expression in patients with cancer.
METHODOLOGY
PubMed, Embase, Web of Science, Cochrane Library, and Scopus were comprehensively explored from their inception to April 20, 2023, for selecting studies on the clinicopathological and prognostic role of RACK1 in patients with cancer that met the criteria for inclusion in this review. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were used to assess the prognosis-predictive value of RACK1 expression, while pooled odds ratios (ORs) and 95% CIs were used to evaluate the correlation between RACK1 expression and the clinicopathological characteristics of patients with cancer. The quality of the included studies was evaluated using the Newcastle-Ottawa Scale.
RESULTS
Twenty-two studies (13 on prognosis and 20 on clinicopathological characteristics) were included in this systematic review and meta-analysis. The findings indicated that high RACK1 expression was significantly associated with poor overall survival (HR = 1.62; 95% CI, 1.13-2.33; = 0.009; I = 89%) and reversely correlated with disease-free survival/recurrence-free survival (HR = 1.87; 95% CI, 1.22-2.88; = 0.004; I = 0%). Furthermore, increased RACK1 expression was significantly associated with lymphatic invasion/N+ stage (OR = 1.74; 95% CI, 1.04-2.90; = 0.04; I = 79%) of tumors.
CONCLUSIONS
RACK1 may be a global predictive marker of poor prognosis in patients with cancer and unfavorable clinicopathological characteristics. However, further clinical studies are required to validate these findings.
Topics: Humans; Disease-Free Survival; Neoplasm Proteins; Neoplasms; Prognosis; Receptors for Activated C Kinase
PubMed: 37601269
DOI: 10.7717/peerj.15873 -
BMJ Supportive & Palliative Care Dec 2022P-cadherin can act both as a tumour suppressor and an oncogene. The clinical prognostic value of P-cadherin overexpression in breast cancer (BC) remains unclear. We... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
P-cadherin can act both as a tumour suppressor and an oncogene. The clinical prognostic value of P-cadherin overexpression in breast cancer (BC) remains unclear. We conducted a study-level meta-analysis to determine whether P-cadherin expression can help predict prognosis in BC.
METHODS
A systematic literature search was performed to review eligible studies and clarify the relationship between P-cadherin overexpression and overall survival (OS), disease-free survival (DFS), pathological features, molecular subtypes and molecular phenotypes in BC.
RESULTS
Thirty-one studies including 12 332 patients were included. P-cadherin overexpression was correlated with significantly worse OS (HR=1.77, p<0.00001) and DFS (HR=1.96, p0.00001) than P-cadherin-negative. P-cadherin overexpression could lead to high histological grade (OR=3.33, p<0.00001) and lymph node metastasis (OR=1.62, p<0.00001). Moreover, P-cadherin overexpression was associated with low odds of the luminal A subtype and high odds of the human epidermal growth factor receptor-2 (HER2)-positive and triple-negative subtypes. P-cadherin expression led to low expression of oestrogen and progesterone receptor (OR=0.37 and OR=0.36, respectively, both p<0.00001) and high expression of HER2 (OR=2.31, p<0.00001), Ki-67 (OR=2.79, p<0.00001), epidermal growth factor receptor (OR=5.85, p<0.00001) and cytokeratin 5/6 (OR=6.79, p<0.00001).
CONCLUSIONS
P-cadherin was found to be associated with invasiveness and metastasis. P-cadherin expression can probably be a useful biomarker for predicting poor survival and may act as an independent prognostic predictor.
Topics: Humans; Female; Breast Neoplasms; Prognosis; Cadherins; Disease-Free Survival; Lymphatic Metastasis
PubMed: 32943470
DOI: 10.1136/bmjspcare-2020-002204 -
PloS One 2021GPRC5A is associated with various cancer initiation and progression. Controversial findings have been reported about GPRC5A prognostic characteristics, and no... (Meta-Analysis)
Meta-Analysis
BACKGROUND
GPRC5A is associated with various cancer initiation and progression. Controversial findings have been reported about GPRC5A prognostic characteristics, and no meta-analysis has been conducted to assess the relationship between GPRC5A and cancer prognosis. Therefore, the objective of this meta-analysis is to evaluate the overall prognostic effectiveness of GPRC5A.
METHODS
We first conducted a systematic search in the PubMed, Embase, Web of Science, CNKI, Cochrane, and WangFang databases. The hazard ratio (HR) and odds ratios (OR) with 95% CI were then pooled to assess the associations between GPRC5A expression and overall survival (OS), disease-free survival (DFS), event-free survival (EFS), and clinicopathological characteristics. Chi-squared test and I2 statistics were completed to evaluate the heterogeneity in our study. A random-effects model was used when significant heterogeneity existed (I2>50% and p<0.05); otherwise, we chose the fixed-effect model. Subgroup analysis was stratified by tumor type, region, HR obtained measurements, and sample capacity to explore the source of heterogeneity.
RESULTS
In total, 15 studies with 624 patients met inclusion criteria of this study. Our results showed that higher expression of GPRC5A is associated with worse OS (HR:1.69 95%CI: 1.20-2.38 I2 = 75.6% p = 0.000), as well as worse EFS (HR:1.45 95%CI: 1.02-1.95 I2 = 0.0% p = 0.354). Subgroup analysis indicated that tumor type might be the source of high heterogeneity. Additionally, cancer patients with enhanced GPRC5A expression were more likely to lymph node metastasis (OR:1.95, 95%CI 1.33-2.86, I2 = 43.9%, p = 0.129) and advanced tumor stage (OR: 1.83, 95%CI 1.15-2.92, I2 = 61.3%, p = 0.035), but not associated with age, sex, differentiation, and distant metastasis.
CONCLUSION
GPRC5A can be a promising candidate for predicting medical outcomes and used for accurate diagnosis, prognosis prediction for patients with cancer; however, the predictive value of GPRC5A varies significantly according to cancer type. Further studies for this mechanism will be necessary to reveal novel insights into application of GPRC5A in cancers.
Topics: Disease-Free Survival; Humans; Neoplasms; Prognosis; Progression-Free Survival; Publication Bias; Receptors, G-Protein-Coupled
PubMed: 33788883
DOI: 10.1371/journal.pone.0249040