Aspirin in the prevention of colorectal cancer recurrence.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 578-578
Author(s):  
Nimisha Kumari ◽  
Hiren A. Mandaliya ◽  
Tiffany Evans ◽  
Patrick McElduff ◽  
Christopher Oldmeadow ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Regression Model ◽  
Propensity Scores ◽  
Cox Regression ◽  
Colorectal Adenomas ◽  
Stage Ii ◽  
Single Institution ◽  
Relapse Free Survival ◽  
Free Survival

578 Background: Aspirin use reduces the incidence of colorectal adenomas, and of colorectal cancer (CRC) in patients with hereditary non-polyposis colorectal cancer. There is limited data on the effect of aspirin in the secondary prevention of CRC, currently the subject of multiple prospective randomized trials. We aimed to test the hypothesis that aspirin reduces disease recurrence in patients diagnosed with early CRC at a high volume, single institution. Methods: A retrospective analysis was conducted of all patients (pts) treated with at least one cycle of adjuvant chemotherapy for stage II or III CRC over a 5yr period (2009–13). Patients with synchronous CRC were excluded. Aspirin use at the onset of adjuvant chemotherapy was sourced from the universal electronic recording of concomitant medications. Kaplan-Meier curves and the log-rank test were used to compare crude relapse free survival (RFS) between pts who were using aspirin to those who were not. Propensity score analyses was used to balance the groups according to potentially confounding variables: tumor site (colon vs rectum), tumor stage (II vs III), and adjuvant chemotherapy (oxaliplatin-based vs no oxaliplatin). The propensity scores were estimated through a multivariable logistic regression model, and a Cox proportional hazards model used to assess the effect of aspirin use on RFS in the sample weighted according to the inverse probability of receiving aspirin. Results: A cohort of 231 pts met eligibility criteria; median age 64yr; 50% colon, 50% rectal; 19% stage II, 81% stage III; 35% received oxaliplatin; 13% (n=31) were using aspirin and 26% of pts (n=61) developed CRC recurrence in median follow-up of 2.9yr. Unadjusted RFS was not significantly different for those using aspirin (log rank p value 0.88). There was good overlap in propensity scores for the two groups. The hazard ratio for RFS with aspirin use from the weighted Cox regression model was 1.2 (95% CI 0.62-2.29), indicating no statistically significant effect of aspirin on CRC relapse. Conclusions: In this single institution series, we did not find evidence that aspirin use at onset of chemotherapy had an effect on CRC relapse free survival. These results do not exclude an aspirin effect that is modest or restricted to select CRC subgroups.

Outcome of patients with colorectal cancer undergoing lung metastases resection: a single-institution retrospective analysis

2020 ◽  
pp. 030089162093079
Author(s):  
Marco Mammana ◽  
Francesca Bergamo ◽  
Letizia Procaccio ◽  
Marco Schiavon ◽  
Fotios Loupakis ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Cox Regression ◽  
Multivariable Analysis ◽  
Postoperative Chemotherapy ◽  
Single Institution ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Lung Metastasectomy

Introduction: This study was undertaken to review a single-institution cohort of patients with metastatic colorectal cancer undergoing lung resection after a multidisciplinary evaluation and to investigate the main prognostic factors for survival. Methods: Medical records of 129 patients undergoing lung metastasectomy for colorectal cancer with curative intent from 2001 to 2017 were reviewed. Tissue samples from the primary tumor were analyzed with a multiplex genotyping system for the detection of mutations in RAS and BRAF genes. Survival analyses were carried out by the Kaplan-Meier method. Univariate and multivariable analyses were performed using the log-rank test and the Cox regression model. Results: Postoperative morbidity and mortality were 13.2% and 0%, respectively. At a median follow-up time of 62.5 months, median overall survival was 90.5 months and median relapse-free survival was 42.8 months. Multivariable analysis for overall survival identified synchronous versus metachronous metastatic presentation as the only prognostic factor, whereas relapse-free survival was independently associated with synchronous versus metachronous metastatic presentation, number of metastases, and postoperative chemotherapy. Conclusions: This study shows particularly favorable survival outcomes for patients undergoing lung metastasectomy. The validity of some of the main prognostic factors was confirmed and a positive effect of postoperative chemotherapy on relapse-free survival was shown. Contrary to other reports, the presence of KRAS mutations was not associated with significant survival differences. Further studies are needed in order to clarify the interactions between molecular, clinical, and pathologic characteristics and treatment-related factors.

Does microsatellite instability predict the effect of adjuvant chemotherapy in stage III colorectal cancer? A meta-analysis

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4121-4121
Author(s):  
G. Des Guetz ◽  
B. Uzzan ◽  
P. Nicolas ◽  
K. Chouahnia ◽  
G. Perret ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Microsatellite Instability ◽  
Colorectal Neoplasm ◽  
Meta Analysis ◽  
Stage Iii ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Electronic Search ◽  
Survival Difference

4121 Background: Microsatellite instability (MSI) is a prognostic factor in colorectal cancer. Whether it predicts the effect of adjuvant chemotherapy (CT) on overall survival (OS) and relapse-free survival (RFS) is controversial. Methods: Studies were identified by an electronic search using online PubMed, with simultaneous keywords (colorectal neoplasm, microsatellite instability, chemotherapy, prognosis). Abstracts from ASCO and AACR proceedings were reviewed. Articles were obtained from cross-checking of references and from a previous prognostic meta-analysis (MA) (Popat, 2005). We used EasyMA software, available online. A Hazard Ratio (HR) < 1 for MSI-high (MSI-H) status compared with microsatellite stable (MSS) meant a better survival. Results: Our MA found 21 studies (4 abstracts). Statistical calculations were performed in 11 studies (5087 patients including 2879 receiving 5FU-based CT; mean age: 63 years; 1489 stage II, 2648 stage III (64%)). MSI-H was found in 644 patients (15% of total), MSS in 3624. Seven studies (2 randomized) assessed 2 cohorts receiving or not adjuvant CT, 4 studies only included patients receiving CT. Global HR OS (9 studies) was 0.79 (95% confidence interval or CI: 0.64–0.98; p = 0.03). Global HR RFS (8 studies) was 0.67 (95% CI: 0.54–0.83; p < 0.001). A MA on stage III patients (4 studies, 719 patients, 137 MSI-H) found a higher survival among MSI-H than MSS patients receiving CT (HR OS: 0.71, 95% CI 0.49–1.03; HR RFS 0.56, 95% CI 0.42–0.75). Interaction between MSI status and CT status was statistically significant on OS and RFS (4 studies). A MA among MSI-H patients (7 studies) found no survival difference between patients under CT or not: HR OS: 0.70 (95% CI 0.44–1.09), HR RFS: 0.96 (95% CI: 0.62–1.49). Conclusions: Adjuvant CT significantly improved survival in MSI-H compared with MSS patients. MSI-H stage III patients receiving CT survived more than MSS. MSI-H status did not predict response to CT compared with no treatment. No significant financial relationships to disclose.

Tumor cancer stem cell genetic profile as predictor of relapse in stage II and III radically resected colon cancer patients.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 429-429
Author(s):  
Riccardo Giampieri ◽  
Mario Scartozzi ◽  
Cristian Loretelli ◽  
Alessandra Mandolesi ◽  
Alessandro Bittoni ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Cancer Patients ◽  
Stage Ii ◽  
Genetic Profile ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Group A ◽  
Colorectal Cancer Patients ◽  
Risk Of Relapse

429 Background: Although disease stage is the most relevant factor influencing treatment choice in locally advanced radically resected colon cancer, it is not uncommon to observe disease relapse in patients with apparent low risk stage that are usually excluded from an adjuvant therapy. On the contrary we also know that some patients with high risk stage are not likely to relapse, independently from medical treatment received. Preclinical data suggested that cancer stem cells may influence the biological behaviour of many solid tumours including colorectal cancer, we then tested a panel of genetic markers of stemness in resected Dukes stage B and C colorectal cancer patients in order to define a prognostic profile. Methods: We performed k-means unsupervised clustering (K=2) using the mRNA expression data of 66 genes. The algorithm divided the patients into two groups (A and B). Most patients clustered in a manner consistent with relapse free survival, defined as the time between primary surgery and first radiological sign of metastatic involvement or patients death, whichever came first. Results: A total of 62 patients were analysed (36, 58% stage II and 26, 41% stage III), 36 (58%) patients relapsed during the follow-up period (range 1.63-86.5 months). Respectively 12 (19%) and 50 (81%) patients were allocated into group A and B. A significantly different median relapse-free survival was observed between the 2 groups (22.18 vs 42.85 months, p=0.0296). Interestingly, even if group A had a worse outcome in terms of risk of relapse, an higher proportion of stage II patients could be found in this group (83%) when compared with the group B (52%). Among tested genes, those with the highest capability in determining allocation into one of the two groups were CD44, ALCAM, DTX2, HSPA9, CCNA2, PDX1, MYST1, COL1A1 and ABCG2. Conclusions: This analysis supports the idea that, other than (or maybe more than) stage, biological variables, such as expression levels of colon cancer stem cell genes, may be relevant in determining an increased risk of relapse in resected colorectal cancer patients. Our findings may also be relevant for new treatment strategies targeting tumour stem cells genetic profile.

Five-Year Outcomes of a Randomized Phase III Trial Comparing Adjuvant Chemotherapy With S-1 Versus Surgery Alone in Stage II or III Gastric Cancer

2011 ◽  
Vol 29 (33) ◽  
pp. 4387-4393 ◽  
Author(s):  
Mitsuru Sasako ◽  
Shinichi Sakuramoto ◽  
Hitoshi Katai ◽  
Taira Kinoshita ◽  
Hiroshi Furukawa ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Survival Rate ◽  
Adjuvant Chemotherapy ◽  
Stage Ii ◽  
Disease Stage ◽  
Relapse Free Survival ◽  
Free Survival ◽  
End Point

Purpose The first planned interim analysis (median follow-up, 3 years) of the Adjuvant Chemotherapy Trial of S-1 for Gastric Cancer confirmed that the oral fluoropyrimidine derivative S-1 significantly improved overall survival, the primary end point. The results were therefore opened at the recommendation of an independent data and safety monitoring committee. We report 5-year follow-up data on patients enrolled onto the ACTS-GC study. Patients and Methods Patients with histologically confirmed stage II or III gastric cancer who underwent gastrectomy with D2 lymphadenectomy were randomly assigned to receive S-1 after surgery or surgery only. S-1 (80 to 120 mg per day) was given for 4 weeks, followed by 2 weeks of rest. This 6-week cycle was repeated for 1 year. The primary end point was overall survival, and the secondary end points were relapse-free survival and safety. Results The overall survival rate at 5 years was 71.7% in the S-1 group and 61.1% in the surgery-only group (hazard ratio [HR], 0.669; 95% CI, 0.540 to 0.828). The relapse-free survival rate at 5 years was 65.4% in the S-1 group and 53.1% in the surgery-only group (HR, 0.653; 95% CI, 0.537 to 0.793). Subgroup analyses according to principal demographic factors such as sex, age, disease stage, and histologic type showed no interaction between treatment and any characteristic. Conclusion On the basis of 5-year follow-up data, postoperative adjuvant therapy with S-1 was confirmed to improve overall survival and relapse-free survival in patients with stage II or III gastric cancer who had undergone D2 gastrectomy.

Hispanic Ethnicity and the Risk of Pediatric Leukemia Relapse

2017 ◽  
Vol 57 (6) ◽  
pp. 656-659
Author(s):  
Ernest K. Amankwah ◽  
Greg A. Hale
Keyword(s):  
Cox Regression ◽  
Small Sample Size ◽  
Small Sample ◽  
Single Institution ◽  
Relapse Free Survival ◽  
Pediatric Leukemia ◽  
Free Survival ◽  
Hazard Ratios ◽  
Leukemia Relapse ◽  
Study Participants

Limited knowledge currently exists on the disparity in pediatric leukemia relapse. This study compared the risk of pediatric leukemia relapse between Hispanic and non-Hispanic Whites. Study participants were children (<20 years) diagnosed with leukemia from January 2006 to December 2014 at the Johns Hopkins All Children’s Hospital, St. Petersburg, Florida. Hazard ratios and 95% confidence intervals for relapse-free survival were calculated using adjusted Cox regression. The study included 35 Hispanic and 94 non-Hispanic Whites. Among patients <10 years old, there was a significantly higher risk of relapse in Hispanic compared to non-Hispanic Whites (hazard ratio = 6.19, 95% confidence interval = 1.15-33.27). No association was observed for patients aged ≥10 years nor all participants combined. Although the finding of this study may suggest that ethnic disparity in pediatric leukemia relapse may exist in younger children, our finding is limited by the small sample size from a single institution. Therefore, future larger multiinstitutional studies are warranted.

Immunological nomograms predicting prognosis and guiding adjuvant chemotherapy in stage II colorectal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 499-499
Author(s):  
Junjie Peng ◽  
Yaqi Li ◽  
Yang Feng
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Tumor Infiltrating Lymphocytes ◽  
Risk Groups ◽  
High Risk Group ◽  
Stage Ii ◽  
Stage Ii Colorectal Cancer

499 Background: The type, abundance, and location of tumor-infiltrating lymphocytes (TILs) have been associated with prognosis in colorectal cancer. The objective of this study was to assess the prognostic role of TILs and develop a nomogram for accurate prognostication of stage II colorectal cancer. Methods: Immunohistochemistry was conducted to assess the densities of intraepithelial and stromal CD3+, CD8+, CD45RO+ and FOXP3+ TILs, and to estimate PD-L1 expression in tumor cells for 168 patients with stage II colorectal cancer. The prognostic roles of these features were evaluated using COX regression model, and nomograms were established to stratify patients into low and high-risk groups and compare the benefit from adjuvant chemotherapy. Results: In univariate analysis, patients with high intraepithelial or stromal CD3+, CD8+, CD45RO+ and FOXP3+ TILs were associated significantly with better relapse-free survival (RFS) and overall survival (OS), except for stromal CD45RO+ TILs, whereas PD-L1 expression wasn't associated with RFS or OS. In multivariate analysis, patients with high intraepithelial CD3+ and stromal FOXP3+ TILs were associated with better RFS (p < 0.001 and p = 0.032, respectively), while only stromal FOXP3+ TILs was an independent prognostic factor for OS (p = 0.031). The nomograms were well calibrated and showed a c-index of 0.751 and 0.757 for RFS and OS, respectively. After stratifying into low and high-risk groups, the high-risk group exhibited a better OS from adjuvant chemotherapy (3-year OS of 81.9% v 34.3%, p = 0.006). Conclusions: These results may help improve the prognostication of stage II colorectal cancer and identify a high-risk subset of patients who appeared to benefit from adjuvant chemotherapy.

Long Intergenic Non-Coding RNAs (lincRNA) Impacts Biology and Clinical Outcome in Multiple Myeloma

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 642-642
Author(s):  
Mehmet Kemal Samur ◽  
Naim Rashid ◽  
Alice Cleynen ◽  
Mariateresa Fulciniti ◽  
Adam Sperling ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Regression Model ◽  
Cox Regression ◽  
Differentially Expressed ◽  
P Value ◽  
Relapse Free Survival ◽  
Protein Coding ◽  
Free Survival ◽  
Protein Coding Genes ◽  
Regulatory Functions

Abstract RNA has a diverse sets of regulatory functions besides being a messenger between DNA and protein. Recent analysis of RNA repertoire has identified a large numbers of non-coding transcripts. One of which, long intergenic non-coding RNA (lincRNA) with transcripts longer than 200 nucleotides, are located between the protein coding genes and do not overlap exons of either protein-coding or other non-lincRNA genes. lincRNAs have been considered to provide regulatory functions, however, their precise role in cellular biology remains unclear. Here, we have evaluated the lincRNA profile and their clinical role in MM. We performed RNA-seq on CD138+ MM cells from 320 patients and 18 normal bone marrow plasma cells (NBM) and analyzed for lincRNA. Data from Unstranded 50 bp paired-end RNAseq reads were mapped to the human genome and evaluated for frequency and type of lncRNA. Patient data for MM characteristics, cytogenetic and FISH as well as clinical survival outcomes were also analyzed and correlated with lncRNA data. We compared differentially expressed lincRNAs and protein coding genes in MM versus NBM samples. lincRNA and protein coding genes that have more than 2 reads/million reads for at least 50 samples (~15%) were included in the analysis. We identified 192 significantly expressed lincRNA (adj p value <0.05). We evaluated neighborhood protein coding genes for lincRNA within 500kb up/down stream and identified 298 genes within the region, 134 of these also differentially expressed between MM and NBM. Gene enrichment analysis to recognize possible biological processes that may be affected by lincRNAs and genes enriched by several Gene Ontology(GO) terms identified DNA binding, transcription, cell proliferation, and regulation of lymphocyte function. We applied unsupervised clustering method to the differentially expressed lincRNA that are neighbor of these 134 protein-coding genes. We identified four distinct clusters which are being investigated for correlation with clinical subtypes of MM. Finally we checked correlation between lincRNAs and clinical outcome including response and relapse free survival. We compared differentially expressed lincRNA between patients achieving complete response (CR) versus others and identified 16 lincRNAs with significantly different expression values (p value < 0.05). Using univariate cox regression model, 26 lincRNAs were identified as having significant correlation (cox p value < 0.05) with event-free survival (EFS). Three of these lincRNAs were also related with response prediction suggesting high level of functional and biological importance. We have developed a multivariate cox regression model utilizing these individually significant lincRNAs able to predict relapse free survival (Overall Wald test p value = 6.736e-07). Using a training set of 171 patients, we developed a cox regression multivariate survival model and created a risk score. The high and low risk based on lincRNA was validated using this model in 85 independent patients (log-rank p = 0.04). We are in the process of now integrating the gene expression data with lincRNA data to develop an integrated survival model. In summary, we report the first differential lincRNA expression in MM showing a significant role in disease biology as well as clinical outcome. lincRNAs are still functionally poorly characterized and our ongoing integrative approach will provide a link between lincRNAs and protein coding genes in MM. Disclosures Anderson: Celgene: Consultancy; Sanofi-Aventis: Consultancy; Onyx: Consultancy; Acetylon: Scientific Founder, Scientific Founder Other; Oncoprep: Scientific Founder Other; Gilead Sciences: Consultancy.

scholarly journals GADD45B as a Prognostic and Predictive Biomarker in Stage II Colorectal Cancer

Genes ◽  
2018 ◽  
Vol 9 (7) ◽  
pp. 361 ◽  
Author(s):  
Zhixun Zhao ◽  
Yibo Gao ◽  
Xu Guan ◽  
Zheng Liu ◽  
Zheng Jiang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Damage ◽  
Adjuvant Chemotherapy ◽  
Prognostic Factor ◽  
Expression Patterns ◽  
Independent Prognostic Factor ◽  
Stage Ii ◽  
Free Survival ◽  
Cox Regression Analysis ◽  
Stage Ii Colorectal Cancer

GADD45B acts as a member of the growth arrest DNA damage-inducible gene family, which has demonstrated to play critical roles in DNA damage repair, cell growth, and apoptosis. This study aimed to explore the potential relationship between GADD45B expression and tumor progression and evaluate the clinical value of GADD45B in stage II colorectal cancer (CRC). The expression patterns and prognostic value of GADD45B in CRC were analyzed based on The Cancer Genomic Atlas (TCGA). GADD45B expression features of 306 patients with stage II CRC and 201 patients with liver metastasis of CRC were investigated using immunochemical staining on tissue microarrays. Afterward, survival analysis and stratification analysis were performed in stage II to explore the prognostic and predictive significance of GADD45B. Overexpressed GADD45B is associated with poorer prognosis for CRC patients both in overall survival (OS) (p < 0.001) and disease-free survival (DFS) (p = 0.001) based on the TCGA database. Analysis results according to the stage II CRC cohort and the liver metastatic CRC cohort revealed that GADD45B was gradually upregulated in normal mucosa including primary colorectal cancer (PCC). Colorectal liver metastases (CLM) tissues were arranged in order (normal tissue vs. PCC p = 0.005 and PCC vs. CLM p = 0.001). The low GADD45B group had a significantly longer five-year OS (p = 0.001) and progression-free survival (PFS) (p < 0.001) than the high GADD45B group for the stage II patients. The multivariate Cox regression analysis results proved that the expression level of GADD45B was an independent prognostic factor for stage II after radical surgery (OS: Hazard Ratio (HR) 0.479, [95% confidence interval (CI) 0.305–0.753] and PFS:HR 0.490, [95% CI 0.336–0.714]). In high GADD45B expression subgroup of stage II cohort, the patients who underwent adjuvant chemotherapy had longer PFS than those who did not (p = 0.008). High expression levels of GADD45B is an independent prognostic factor of decreased OS and PFS in stage II CRC patients. The stage II CRC patients with high GADD45B expression might benefit from adjuvant chemotherapy.

Analysis of dose intensity for adjuvant chemotherapy trials in stage II breast cancer.

1986 ◽  
Vol 4 (8) ◽  
pp. 1162-1170 ◽  
Author(s):  
W Hryniuk ◽  
M N Levine
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Dose Intensity ◽  
Stage Ii ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Clear Cut ◽  
Prognostic Groups ◽  
Survival Studies ◽  
The Relationship

We have analyzed the relationship between dose intensity of cyclophosphamide, methotrexate, and fluorouracil (CMF)-containing adjuvant chemotherapy of stage II breast cancer and 3-year relapse-free survival. Studies using only one or two drugs of CMF or melphalan instead of cyclophosphamide were included in the analysis by using simple techniques developed for this purpose. There was a clear-cut relationship between relapse-free survival and dose intensity in trials containing all four prognostic groups: less than 50 years, one to three and more than three positive nodes; and greater than or equal to 50 years, one to three and more than three positive nodes (P less than 10(-5)). Relapse-free survival also correlated with dose intensity for each of the four prognostic groups analyzed separately (P less than .005). Dose intensity was an independently significant correlate of relapse-free survival in multivariate analysis (P less than 10(-5)). This is a retrospective study, and the hypothesis that dose intensity contributes to outcome independently of other variables should be tested prospectively. Methods of increasing dose intensity also require testing in randomized trials before they can be applied to routine clinical practice.

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