MSI-GC-01: Individual patient data (IPD) meta-analysis of microsatellite instability (MSI) and gastric cancer (GC) from four randomized clinical trials (RCTs).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 66-66 ◽  
Author(s):  
Filippo Pietrantonio ◽  
Alessandra Raimondi ◽  
Yoon Young Choi ◽  
WonKi Kang ◽  
Ruth E. Langley ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Immune Checkpoint Blockade ◽  
Free Survival ◽  
N Stage ◽  
Predictive Role ◽  
Multivariable Analyses ◽  
Low Prevalence

66 Background: In CLASSIC and MAGIC, MSI was a good prognostic factor, and adjuvant/perioperative chemotherapy had null/detrimental effect. Given the low prevalence of MSI in GCs and its association with other good prognostic variables, larger datasets are needed to draw more robust evidences on its specific prognostic/predictive impact. Methods: This was a multinational IPD meta-analysis of resectable GC pts enrolled in MAGIC, CLASSIC, ARTIST, ITACA-S. Data on pts’ demographics (age, sex, and race), primary site (stomach versus junctional), histotype (intestinal vs. other), T/N stage (7th TNM), treatment received (multimodal therapy vs. surgery alone) and MSI were pooled. Univariable and multivariable associations with disease-free survival (DFS)/overall survival (OS) were assessed. The predictive role of MSI according to treatment received was assessed overall and in the 2 RCTs with a surgery alone arm (MAGIC+CLASSIC). Results: We pooled 1,552 pts with available MSI status: 121 (7,8%) were MSI, 572 Caucasian/980 Asian. In MSI versus MSS subgroups, 5-y DFS was 71.8% (95% CI: 63.8-80.7%) versus 52.3% (49.6-55.0%) (HR = 0.50, 95% CI 0.35-0.72; p < 0.001); 5-y OS 77.4% (69.9-85.8%) versus 59.2% (56.6-62.0%) (HR = 0.50, 95% CI 0.34-0-74; p < 0.001). In multivariable analyses, MSI was independently associated with DFS (HR = 0.48 [0.33-0.70]; p < 0.001) and OS (HR = 0.48 [0.29-0.81]; p = 0.005), as T/N/race/treatment. Conclusions: In resectable primary GC, MSI is an independent good prognostic marker that should be adopted as stratification factor in future RCTs. Chemotherapy omission and/or immune checkpoint blockade should be prospectively investigated in MSI-high GCs according to the clinically-defined risk of relapse. [Table: see text]

scholarly journals Prognosis Value of Low microRNA-34a Expression in Human Gastrointestinal Cancer: A Meta-Analysis

2020 ◽  
Author(s):  
Yan-Ling Chen ◽  
Xiao-Lin Liu ◽  
Ling Li
Keyword(s):  
Meta Analysis ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
Cancer Prognosis ◽  
Expression Level ◽  
Significant Relation ◽  
Free Survival ◽  
Predictive Role ◽  
Disease Free

Abstract Background: Mounting evidence shows that microRNA-34a (miR-34a) is involved in cancer prognosis. Therefore, we summarize the predictive role of miR-34a for survival in patients with gastrointestinal cancers (GICs). Methods: All the eligible studies were searched by PubMed, Web of Science and EMBASE and survival results were extracted. Then, the hazard ratio (HR) with corresponding 95% confidence intervals (CIs) was calculated to evaluate the prognostic role of miR-34a in GICs. The association between miR-34a expression and clinicopathological characteristics was estimated by odds ratio (OR) and 95%CIs. Results: A total of 20 studies were included in this meta-analysis. For overall survival (OS), the lower miR-34a expression significantly predicted poorer outcome in GICs, with the pooled HR of 1.86 (95% CI: 1.52-2.28, P<0.01). For disease-free survival (DFS), progressive-free survival (PFS), and recurrence-free survival (RFS), the lower miR-34a expression revealed worse DFS/PFS/RFS with the pooled HR of 1.86 (95% CI: 1.31–2.63, P < 0.01). Significant relation of differentiation/TMN stage/lymphatic metastasis and the expression level of miR-34a was identified. Conclusion: This meta-analysis reveals that lower miR-34a expression is significantly connected with worse OS and DFS/PFS/RFS of GICs patients. In addition, miR-34a expression level is relatively lower in patients with lymph node metastasis than patients without, and decreased miR-34a expression level is linked to poor tumor differentiation and late TMN stage. MiR-34a may become a new factor for prognosis prediction and progression of GICs.

Expression of tripartite motif-containing 44 and its prognostic and clinicopathological values in human malignancies: a meta-analysis

2020 ◽  
Author(s):  
Guoliang Xiao ◽  
Qiuxi Yang ◽  
Ziwei Bao ◽  
Haixia Mao ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Clinical Stage ◽  
Disease Free Survival ◽  
Advanced Clinical Stage ◽  
Free Survival ◽  
Over Expression ◽  
Tumor Tissues ◽  
Tripartite Motif ◽  
Predictive Role

Abstract Background: Previous researches reported that tripartite motif-containing 44 (TRIM44) were related to prognosis in multiple human tumors. This study was designed to systematically assess the prognostic value of TRIM44 in human malignancies and to describe its possible mechanisms of oncogenesis.Methods: available databases worldwide were searched for eligible studies that evaluated the clinicopathological and prognostic roles of TRIM44 in patients with malignancies.The hazard ratio (HR) and combined odds ratios (ORs) were combined to assess the predictive role of TRIM44 using Stata/SE 14.1 software.Results: A total of 1,740 patients from thirteen original studies were included in this study finally. The results of the combined analysis showed that over-expression of TRIM44 was significantly correlated with shorter overall survival (OS) in cancer patients (HR = 2.16, 95% CI: 1.65–2.83) as well as worse disease-free survival (DFS) (HR= 2.13 (95% CI 1.45 3.11). Additionally, the combined ORs indicated that elevated TRIM44 expression was significantly associated with lymph node metastasis (OR=2.69, 95% CI: 1.71–4.24), distant metastasis (OR=10.35, 95% CI: 1.01-106.24), poor tumor differentiation (OR=1.78, 95% CI: 1.03–3.09), high depth of tumor invasion (OR=2.72, 95% CI: 1.73–4.30), advanced clinical stage (OR=2.75, 95% CI: 2.04-3.71), and recurrence (OR=2.30, 95% CI: 1.34–3.95). Analysis of expression using GEPIA indicated that the expression of TRIM44 was higher in most tumor tissues than the corresponding normal tissues.Survival analysis indicated high levels of TRIM44 mRNA were associated with unfavorable OS and DFS in various malignancies .Conclusions: TRIM44 may serve as a valuable prognostic biomarker and a potential therapeutic target for patients with malignancies.

scholarly journals Individual Patient Data Meta-Analysis of the Value of Microsatellite Instability As a Biomarker in Gastric Cancer

2019 ◽  
Vol 37 (35) ◽  
pp. 3392-3400 ◽  
Author(s):  
Filippo Pietrantonio ◽  
Rosalba Miceli ◽  
Alessandra Raimondi ◽  
Young Woo Kim ◽  
Won Ki Kang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Microsatellite Instability ◽  
Individual Patient Data ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Immune Checkpoint Blockade ◽  
Patient Data ◽  
High Status ◽  
Predictive Role

PURPOSE In the CLASSIC and MAGIC trials, microsatellite instability (MSI)–high status was a favorable prognostic and potential negative predictive factor for neoadjuvant/adjuvant chemotherapy in resectable gastric cancer (GC). Given the low prevalence of MSI-high status in GC and its association with other positive prognostic variables, large data sets are needed to draw robust evidence of its prognostic/predictive value. PATIENTS AND METHODS We performed a multinational, individual-patient-data meta-analysis of the prognostic/predictive role of MSI in patients with resectable GC enrolled in the MAGIC, CLASSIC, ARTIST, and ITACA-S trials. Prognostic analyses used multivariable Cox models (MVM). The predictive role of MSI was assessed both in an all-comer population and in MAGIC and CLASSIC trials by MVM testing of the interaction of treatment (chemotherapy plus surgery v surgery) with MSI. RESULTS MSI status was available for 1,556 patients: 121 (7.8%) had MSI-high status; 576 were European, and 980 were Asian. In MSI-high versus MSI-low/microsatellite stable (MSS) comparisons, the 5-year disease-free survival (DFS) was 71.8% (95% CI, 63.8% to 80.7%) versus 52.3% (95% CI, 49.7% to 55.1%); the 5-year overall survival (OS) was 77.5% (95% CI, 70.0% to 85.8%) versus 59.3% (95% CI, 56.6% to 62.1%). In MVM, MSI was associated with longer DFS (hazard ratio [HR], 1.88; 95% CI, 1.28 to 2.76; P < .001) and OS (HR, 1.78; 95% CI, 1.17 to 2.73; P = .008), as were pT, pN, ethnicity, and treatment. Patients with MSI-low/MSS GC benefitted from chemotherapy plus surgery: the 5-year DFS compared with surgery only was 57% versus 41% (HR, 0.65; 95% CI, 0.53 to 0.79), and the 5-year OS was 62% versus 53% (HR, 0.75; 95% CI, 0.60 to 0.94). Conversely, those with MSI-high GC did not: the 5-year DFS was 70% versus 77% (HR, 1.27; 95% CI, 0.53 to 3.04), and the 5-year OS was 75% versus 83% (HR, 1.50; 95% CI, 0.55 to 4.12). CONCLUSION In patients with resectable primary GC, MSI is a robust prognostic marker that should be adopted as a stratification factor by clinical trials. Chemotherapy omission and/or immune checkpoint blockade should be investigated prospectively in MSI-high GCs according to clinically and pathologically defined risk of relapse.

scholarly journals Prognostic Role of High Stathmin 1 Expression in Patients with Solid Tumors: Evidence from a Meta-Analysis

2018 ◽  
Vol 50 (1) ◽  
pp. 66-78 ◽  
Author(s):  
Qingyan Mao ◽  
Zhen Chen ◽  
Kun Wang ◽  
Renfang Xu ◽  
Hao Lu ◽  
...  
Keyword(s):  
English Literature ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Free Survival ◽  
Online Databases ◽  
Stathmin 1 ◽  
Tumor Types ◽  
Disease Free

Background/Aims: Several recent studies have demonstrated that Stathmin 1expression may be closely associated with prognosis in patients with various types of cancers. In the present study, we conducted a meta-analysis of all available studies in the English literature to assess the prognostic value of Stathmin 1expression in patients with solid cancers. Methods: The online databases PubMed, Embase, and Web of Science were searched for literature regarding Stathmin 1 and its association with patient outcomes associated with solid cancers. Results: A total of 23 articles including 26 studies that contained 5 335 patients were retrieved and analyzed. Our results indicated that high Stathmin 1 expression yielded a worse overall survival (OS) (hazard ratio [HR] = 2.17, 95% confidence interval [CI]: 1.81–2.60), disease-free survival (DFS) (HR = 2.46, 95% CI: 2.00–3.02), disease-specific survival (DSS) (HR = 1.98, 95% CI: 1.58– 2.47) and progression-free survival (PFS)/recurrence-free survival (RFS) (HR = 2.09, 95% CI: 1.51–2.89). Furthermore, the association of high Stathmin 1 expression with poor survival was significant even for sub-group analyses of different tumor types, ethnicities, methods used to calculate HRs, detected methods, and analysis types. Conclusion: In summary, this meta-analysis determined that high Stathmin 1 expression is associated with poor prognosis in patients with solid cancers and expression of this protein could be a clinically useful prognostic biomarker.

Tamoxifen (T) compared to placebo (P), after adjuvant chemotherapy (CT), in premenopausal women with early breast cancer (EBC): Interim results of NCIC-CTG MA.12

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 547-547 ◽  
Author(s):  
V. H. Bramwell ◽  
K. I. Pritchard ◽  
D. Tu ◽  
K. Tonkin ◽  
H. Vachhrajani ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Disease Free Survival ◽  
Premenopausal Women ◽  
Free Survival ◽  
Post Surgery ◽  
Improved Outcomes ◽  
Stopping Treatment ◽  
Safety Monitoring Committee

547 Background: In the early 1990’s, the role of adjuvant T in premenopausal women with EBC had not been clearly established. The efficacy of adjuvant T in hormone receptor (H) negative EBC was unclear. Methods: Eligible premenopausal women with node (N) +ve/high risk N -ve EBC, any H status, post surgery, received standard adjuvant CT (AC ×4, CMF ×6, CEF x6) then were randomized to T (20 mg/day) or P for 5 yrs. Overall survival (OS), disease-free survival (DFS) and toxicity/compliance were evaluated. Original sample size was 800 pts but based on slow accrual was reduced to 660. Mortality rate is lower than anticipated, and Data Safety Monitoring Committee approved reporting results after second interim analysis (152 deaths). Results: 1993–2000, 672 women randomized, median follow-up 8.4 yrs. For T vs P, 5 yr OS 87% vs 82% [Hazard Ratio HR 0.81 (95% CI 0.58–1.12), p = 0.19] and 5 yr DFS 78% vs 71% [HR 0.79 (95% CI 0.61–1.03), p = 0.09]. HR for OS (0.87 vs 0.78, p = 0.71) and DFS (0.79 vs 0.77, p = 0.87) were not significantly different for H +ve and H -ve tumors respectively. Compliance with T/P was suboptimal, 29% women stopping treatment within 2 yrs, and only 53% completing 5 yrs. Conclusions: Current results show only a trend towards improved DFS for premenopausal women with EBC who receive T after adjuvant CT. Other studies of similar design have shown improved DFS, but not OS, and meta-analysis may be more informative. Issues affecting results (slow accrual, improved outcomes for EBC, poor compliance, additional therapies) will be discussed. [Table: see text] [Table: see text]

Prognostic Significance of microRNA-221/222 Expression in Cancers: Evidence from 1,204 Subjects

2014 ◽  
Vol 29 (2) ◽  
pp. 129-141 ◽  
Author(s):  
Jin Wang ◽  
Sha Liu ◽  
Guo Ping Sun ◽  
Fang Wang ◽  
Yan Feng Zou ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Published Data ◽  
Cancer Type ◽  
Free Survival ◽  
Patients With Cancer ◽  
Elevated Expression ◽  
Strength Of Association

Background The prognostic significance of the expression of the miR-221/222 family in cancer remains controversial. We here performed a meta-analysis of published data investigating the effects of miR-221/222 expression on both overall survival (OS) and disease-free survival (DFS) among patients with cancer. Methods A systematic search of the PubMed, Embase, Cochrane, and CNKI databases was performed with the last search being updated on March 15, 2013. The hazard ratio (HR) and its 95% confidence interval (95% CI) were used to assess the strength of association. Results A total of 17 studies involving 1,204 subjects were included in this meta-analysis. When assessing the prognostic significance of miR-221 expression, the pooled HR was 1.91 (95% CI: 1.28-2.85, p=0.002) for OS and 1.36 (95% CI: 0.88-2.09, p=0.163) for DFS. When assessing the prognostic significance of miR-222 expression, the pooled HR was 2.15 (95% CI: 1.51-3.06, p<0.0001) for OS and 1.37 (95% CI: 0.45-4.13, p=0.581) for DFS. We also found that an elevated miR-221 expression was significantly associated with poor OS when stratifying by ethnicity, cancer type, statistical methodology, sample, and quality assessment. There was no evidence of publication bias. Conclusion The meta-analysis demonstrates that the elevated expression of miR-221 and miR-222 is associated with poor OS in patients with cancer. The miR-221/222 cluster might be used as a potential therapeutic strategy in clinical practice. More work is required to fully elucidate the role of the miR-221/222 family in human tumors.

scholarly journals Expression of tripartite motif‑containing 44 and its prognostic and clinicopathological value in human malignancies：a meta-analysis

2020 ◽  
Author(s):  
Guoliang Xiao ◽  
Qiuxi Yang ◽  
Ziwei Bao ◽  
Haixia Mao ◽  
Yi Zhang ◽  
...  
Keyword(s):  
Meta Analysis ◽  
Clinical Stage ◽  
Disease Free Survival ◽  
Advanced Clinical Stage ◽  
Over Expression ◽  
Interactive Analysis ◽  
Tumor Tissues ◽  
Tripartite Motif ◽  
Predictive Role

Abstract Background: Previous researches have reported that tripartite motif-containing 44 (TRIM44) is related to the prognosis of multiple human tumors. This study was designed to systematically assess the prognostic value of TRIM44 in human malignancies and to describe its possible mechanisms of oncogenesis. Methods: The available databases worldwide were searched for eligible studies that evaluated the clinicopathological and prognostic roles of TRIM44 in patients with malignancies.The hazard ratio (HR) and combined odds ratios (ORs) were combined to assess the predictive role of TRIM44 using Stata/SE 14.1 software. Results: A total of 1,740 patients from thirteen original studies were finally included in this study . The results of the combined analysis showed that over-expression of TRIM44 was significantly correlated with shorter overall survival (OS) in cancer patients (HR = 2.16, 95% CI: 1.65–2.83) as well as worse disease-free survival (DFS) (HR= 2.13 (95% CI 1.45–3.11). Additionally, the combined ORs indicated that elevated TRIM44 expression was significantly associated with lymph node metastasis (OR=2.69, 95% CI: 1.71–4.24), distant metastasis (OR=10.35, 95% CI: 1.01-106.24), poor tumor differentiation (OR=1.78, 95% CI: 1.03–3.09), increased depth of tumor invasion (OR=2.72, 95% CI: 1.73–4.30), advanced clinical stage (OR=2.75, 95% CI: 2.04-3.71), and recurrence (OR=2.30, 95% CI: 1.34–3.95). Analysis of expression using Gene Expression Profiling Interactive Analysis (GEPIA) indicated that the expression of TRIM44 was higher in most tumor tissues than in the corresponding normal tissues.Survival analysis indicated high levels of TRIM44 mRNA were associated with unfavorable OS and DFS in various malignancies. Conclusions: TRIM44 may serve as a valuable prognostic biomarker and a potential therapeutic target for patients with malignancies.

scholarly journals The Impact of Post-Operative Radiotherapy in Early Stage (pT1-pT2N0M0) Oral Tongue Squamous Cell Carcinoma in Era of DOI

Cancers ◽  
2021 ◽  
Vol 13 (19) ◽  
pp. 4851
Author(s):  
Daniela Alterio ◽  
Pasqualina D’Urso ◽  
Stefania Volpe ◽  
Marta Tagliabue ◽  
Rita De Berardinis ◽  
...  
Keyword(s):  
Malignant Tumors ◽  
Early Stage ◽  
Postoperative Radiotherapy ◽  
Multivariable Analysis ◽  
Disease Free Survival ◽  
Free Survival ◽  
Multivariable Analyses ◽  
Tumors Classification ◽  
The Impact

Background: This study investigated the role of depth of infiltration (DOI) as an independent prognosticator in early stage (T1-T2N0M0) oral cavity tumors and to evaluate the need of postoperative radiotherapy in the case of patients upstaged to pT3 for DOI > 10 mm in the absence of other risk factors. Methods: We performed a retrospective analysis on patients treated with surgery and re-staged according to the 8th edition of malignant tumors classification (TNM). The role of DOI as well as other clinical/pathological features was investigated at both univariable and multivariable analyses on overall survival (OS), disease free survival (DFS), relapse free survival (RFS), and local RFS. Results: Among the 94 included patients, 23 would have been upstaged to pT3 based on DOI. Multivariable analysis showed that DOI was not an independent prognostic factor for any of the considered outcomes. The presence of perineural invasion was associated with a significant worse RFS (p = 0.02) and LRFS (p = 0.04). PORT was found to be significantly associated with DFS (p = 0.04) and RFS (p = 0.06). Conclusions: The increasing DOI alone was not sufficient to impact the prognosis, and therefore, should not be sufficient to dictate PORT indications in early-stage patients upstaged on the sole basis of DOI.

scholarly journals Prognostic value of Ki-67 in nasopharyngeal carcinoma: a meta-analysis

2021 ◽  
Author(s):  
Yulin Li ◽  
Liang Yue ◽  
Yanqing Li ◽  
Qinxiu Zhang ◽  
Xin Liang
Keyword(s):  
Nasopharyngeal Carcinoma ◽  
Prognostic Value ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Ki 67 ◽  
Free Survival ◽  
Prognostic Effect ◽  
Study Designs ◽  
Local Recurrence Free Survival

The prognostic value of Ki-67 in nasopharyngeal carcinoma (NPC) was controversial according to previous studies. We aimed to clarify the association between K-67 expression and survival in NPC through meta-analysis. We conducted a meta-analysis to explore the potential prognostic effect of Ki-67 on overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS) in NPC. A total of 13 studies comprising 1314 NPC patients were included. High Ki-67 expression was associated with poor OS (hazard ratio [HR]=2.70, 95% confidence interval [CI]=1.97–3.71, p&lt;0.001), DFS (HR=1.93, 95% CI=1.49–2.50, p&lt;0.001), and LRFS (HR=1.86, 95% CI=1.11–3.12, p=0.019). However, there was no significant association between Ki-67 and DMFS (HR=1.37, 95% CI=0.78–2.38, p=0.270). Furthermore, the prognostic role of Ki-67 was maintained throughout different sample sizes, analyses of HR, and study designs for OS and DFS in various subgroups. Elevated Ki-67 expression is a reliable prognostic factor for poorer survival outcomes in NPC.

scholarly journals Role of MicroRNA-124 as a Prognostic Factor in Multiple Neoplasms: A Meta-Analysis

2019 ◽  
Vol 2019 ◽  
pp. 1-12
Author(s):  
Zijian Zhou ◽  
Jiancheng Lv ◽  
Jingzi Wang ◽  
Hao Yu ◽  
Hongcheng Lu ◽  
...  
Keyword(s):  
Large Scale ◽  
Meta Analysis ◽  
Disease Free Survival ◽  
Progression Free Survival ◽  
Protective Role ◽  
Cochrane Library ◽  
Free Survival ◽  
Multiple Neoplasms ◽  
Microrna 124

Objective. MicroRNA-124 (miR-124) was revealed to be an attractive prognostic tumour biomarker in recent studies. However, the results remain inconclusive. Hence, this meta-analysis was carried out to clarify the precise predictive value of miR-124. Materials and Methods. Relevant studies were searched in PubMed, EMBASE, Web of Science, and the Cochrane Library up to October 2018. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were extracted from the selected studies. Results. A total of 29 articles investigating the correlation between miR-124 expression and prognosis were initially identified. The pooled HR for overall survival (OS) of high miR-124 expression in multiple cancers was 0.55 (95%CI=0.50–0.61). Disease-free survival (DFS)/progression-free survival (HR=0.48, 95%CI=0.38–0.61) revealed a protective role of increased miR-124 expression. Epigenetic hypermethylation of miR-124 mediated the silencing of its expression, which is correlated significantly with unfavourable survival (OS: HR=2.06, 95%CI=1.68–2.53; DFS/recurrence-free survival: HR=2.77, 95%CI=1.85–4.16). Conclusions. Taken together, our results suggest that miR-124 plays an antioncogenic role in various tumors, such as lung cancer and colorectal cancer. If methylation of miR-124 could be prevented, progression and metastasis would be improved; thus, miR-124 may be a promising biomarker and novel therapeutic target. Further large-scale studies are needed to confirm this possible effect.

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