Validation of lymphocyte to monocyte ratio in resected small bowel adenocarcinoma as a predictor of survival.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15799-e15799
Author(s):  
Brandon M. Huffman ◽  
Zhaohui Jin ◽  
Siddhartha Yadav ◽  
Shruti Patel ◽  
Amit Mahipal ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Small Bowel ◽  
Predictive Value ◽  
P Value ◽  
Small Bowel Adenocarcinoma ◽  
Training Set ◽  
Lymphocyte To Monocyte Ratio ◽  
Negative Prognostic Factor ◽  
Resected Small Bowel

e15799 Background: Lymphocyte to monocyte ratio (LMR) has been described as a prognostic factor in many solid tumors including colorectal adenocarcinoma. LMR has not been investigated as a prognostic factor in small bowel cancers. In this study, we aimed to evaluate prognostic factors in resected small bowel adenocarcinoma including LMR. Methods: Two hundred forty-one patients who underwent resection for stage I-III small bowel adenocarcinoma were retrospectively identified utilizing the pathology database at a single tertiary referral institution from 1994 to 2015. All patients had complete follow up data and were included in the survival analysis. One hundred sixty-nine patients had preoperative peripheral blood counts available for analysis. Plot of martingale residuals against LMR were used to establish best cutoff points for LMR. A training set for LMR included consecutively identified patients from 2006 to 2015, and a validation cohort including patients identified from 1994 to 2005 was used. Overall survival was performed utilizing Kaplan-Meier method, and Wilcoxon tests were used for statistical comparisons. Cox proportional hazards were performed and all tests were two sided. P value of < 0.05 was considered significant. Results: Median overall survival for the entire group was 54.5 months (95% CI: 37.2-81.2 months) with 5- and 10-year overall survival of 48% and 35%. The training set for LMR included 81 patients, and the validation set included 88 patients. The cutoff of 1.56 was chosen based on most significant p value (p = 0.002). When combined, the overall area under the curve (AUC) for LMR was 0.63, p < 0.01, (specificity 37.3%, sensitivity 90.1%, positive predictive value 33.1%, and negative predictive value 92.2%). There were 126 patients with LMR > 1.56 and 43 patients with LMR < 1.56 in the entire cohort. In multivariate analysis, LMR under 1.56 was a negative prognostic factor, HR = 2.20 (95% CI: 1.27-3.84, p < 0.01). In addition to LMR, age > 60 years and advanced T stage were independently negative predictors of overall survival in all patients. Conclusions: Lymphocyte-to-monocyte ratio < 1.56 is a validated negative prognostic factor in resected small bowel adenocarcinoma.

Lymphocyte-to-monocyte ratio and neutrophil-to-lymphocyte ratio independently predict survival in resected small bowel adenocarcinoma.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 426-426
Author(s):  
Brandon M. Huffman ◽  
Shruti Patel ◽  
Siddhartha Yadav ◽  
Zhaohui Jin ◽  
Amit Mahipal
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Small Bowel ◽  
Tumor Size ◽  
Neutrophil To Lymphocyte Ratio ◽  
Stage I ◽  
Small Bowel Adenocarcinoma ◽  
Lymphocyte Ratio ◽  
Lymphocyte To Monocyte Ratio ◽  
Resected Small Bowel

426 Background: Small bowel adenocarcinoma is a rare malignancy affecting approximately 2,000 patients per year. There is a paucity of evidence prognosticating patients with small bowel adenocarcinoma. We aimed to evaluate multiple factors in patients with resected small bowel adenocarcinoma to determine any association with survival outcomes. Methods: Ninety three patients who underwent resection for stage I-III small bowel adenocarcinoma were retrospectively identified utilizing the pathology database at a single tertiary referral institution. All patients had complete follow up data and were included in the survival analysis. JMP software was used for statistical analysis. Overall survival was performed utilizing Kaplan-Meier method, and log-rank tests were used for statistical comparisons. Cox proportional hazards were performed to control for age, gender, location of tumor, tumor size, tumor stage, and adjuvant therapy. Sensitivity analysis was performed to establish best cutoff points for continuous variables. All tests were two sided and a P value of < 0.05 was considered significant. Results: The median age at diagnosis was 65 years (range 32-90). 61% were male. Median tumor size was 4.5 cm. There were 20, 36, and 37 patients with stage I, stage II, and stage III disease, respectively. Median overall survival (OS) was 151 months, 104 months, and 44 months for stages I, II, and III disease. In a multivariate analysis, independent predictor factors included presurgical lymphocyte to monocyte ratio (LMR) > 4.0, with a Hazard Ratio (HR) 0.13 (95% CI 0.007-0.69, p = 0.01), presurgical neutrophil to lymphocyte ratio (NLR) < 8.0, HR 0.39 (95% CI 0.17-0.96, p = 0.04), and tumor size < 7.5 cm, HR 0.22 (95% CI 0.07-0.85, p = 0.03). Stage, age, T stage, and N stage influenced overall survival in univariate analysis, but were not statistically significant on multivariate analysis. Conclusions: LMR and NLR independently predict survival in patients with resected small bowel adenocarcinoma.

Adjuvant chemotherapy impact on the overall survival of completely resected small bowel adenocarcinoma: An updated meta-analysis.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16806-e16806
Author(s):  
Philip A. Haddad ◽  
Dalia A. Hammoud ◽  
Kevin M. Gallagher
Keyword(s):  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Small Bowel ◽  
Survival Benefit ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Adjuvant Chemoradiotherapy ◽  
Small Bowel Adenocarcinoma ◽  
The Impact ◽  
Resected Small Bowel

e16806 Background: While the small intestine represents around 75% of the length and more than 90% of the gastrointestinal tract mucosal surface, it contributes around 2% of gastrointestinal tumors. Adenocarcinoma which constitutes 40% of all small bowel tumors is the most common histology. Complete surgical resection of early-stage small bowel adenocarcinoma (SBAC) is the only proven potentially curative therapy. Due to the rarity of this disease and the absence of randomized trials, the benefit of postoperative adjuvant chemotherapy (ACT) in patients with completely resected localized SBAC has been controversial. A meta-analysis conducted in 2018 found no survival benefit for adjuvant therapies in SBAC. However, this meta-analysis combined studies that used adjuvant chemotherapy and chemoradiotherapy and included studies contaminated by other less chemosensitive histologies and more advanced and sometimes metastatic disease. The purpose of this meta-analysis is to evaluate the impact of ACT on the overall survival (OS) of patients with completely resected SBAC incorporating more recent studies. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of resected small bowel adenocarcinoma, English language, publications from 2000 to the present, and comparative studies reporting OS with hazard ratios (HR) or Kaplan-Meier curves of patients that underwent ACT versus those that did not. Adjuvant chemoradiotherapy studies and those that reported aggregate OS for a cohort with mixed histologies were excluded. A meta-analysis was conducted using an inverse variance method with a random-effects model. Results: Nine retrospective series which included 2082 patients were selected and analyzed. The majority of SBAC patients that received ACT belonged to stages II & III. ACT was found to be significantly associated with better OS in patients with completely resected SBAC (HR 0.66, 95%CI: 0.56-0.78, p < 0.001). Conclusions: This is the first meta-analysis to show that adjuvant chemotherapy is associated with a survival benefit in patients with completely resected small bowel adenocarcinoma. In the absence of randomized clinical trials, this meta-analysis represents the most compelling data supporting the use of ACT in this patient population.

Combining Proteomics and Gene Expression Profiling Identifies Proteins/Genes Associated with Short Overall Survival in Multiple Myeloma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 197-197
Author(s):  
Ricky D Edmondson ◽  
Shweta S. Chavan ◽  
Christoph Heuck ◽  
Bart Barlogie
Keyword(s):  
Gene Expression ◽  
Overall Survival ◽  
Multivariate Analyses ◽  
Rank Test ◽  
P Value ◽  
Newly Diagnosed ◽  
Training Set ◽  
Test Set ◽  
Log Rank Test ◽  
Test Sets

Abstract Abstract 197 We and others have used gene expression profiling to classify multiple myeloma into high and low risk groups; here, we report the first combined GEP and proteomics study of a large number of baseline samples (n=85) of highly enriched tumor cells from patients with newly diagnosed myeloma. Peptide expression levels from MS data on CD138-selected plasma cells from a discovery set of 85 patients with newly diagnosed myeloma were used to identify proteins that were linked to short survival (OS < 3 years vs OS ≥ 3 years). The proteomics dataset consisted of intensity values for 11,006 peptides (representing 2,155 proteins), where intensity is the quantitative measure of peptide abundance; Peptide intensities were normalized by Z score transformation and significance analysis of microarray (SAM) was applied resulting in the identification 24 peptides as differentially expressed between the two groups (OS < 3 years vs OS ≥ 3 years), with fold change ≥1.5 and FDR <5%. The 24 peptides mapped to 19 unique proteins, and all were present at higher levels in the group with shorter overall survival than in the group with longer overall survival. An independent SAM analysis with parameters identical to the proteomics analysis (fold change ≥1.5; FDR <5%) was performed with the Affymetrix U133Plus2 microarray chip based expression data. This analysis identified 151 probe sets that were differentially expressed between the two groups; 144 probe sets were present at higher levels and seven at lower levels in the group with shorter overall survival. Comparing the SAM analyses of proteomics and GEP data, we identified nine probe sets, corresponding to seven genes, with increased levels of both protein and mRNA in the short lived group. In order to validate these findings from the discovery experiment we used GEP data from a randomized subset of the TT3 patient population as a training set for determining the optimal cut-points for each of the nine probe sets. Thus, TT3 population was randomized into two sub-populations for the training set (two-thirds of the population; n=294) and test set (one-third of the population; n=147); the Total Therapy 2 (TT2) patient population was used as an additional test set (n=441). A running log rank test was performed on the training set for each of the nine probe sets to determine its optimal gene expression cut-point. The cut-points derived from the training set were then applied to TT3 and TT2 test sets to investigate survival differences for the groups separated by the optimal cutpoint for each probe. The overall survival of the groups was visualized using the method of Kaplan and Meier, and a P-value was calculated (based on log-rank test) to determine whether there was a statistically significant difference in survival between the two groups (P ≤0.05). We performed univariate regression analysis using Cox proportional hazard model with the nine probe sets as variables on the TT3 test set. To identify which of the genes corresponding to these nine probes had an independent prognostic value, we performed a multivariate stepwise Cox regression analysis. wherein CACYBP, FABP5, and IQGAP2 retained significance after competing with the remaining probe sets in the analysis. CACYBP had the highest hazard ratio (HR 2.70, P-value 0.01). We then performed the univariate and multivariate analyses on the TT2 test set where CACYBP, CORO1A, ENO1, and STMN1 were selected by the multivariate analysis, and CACYBP had the highest hazard ratio (HR 1.93, P-value 0.004). CACYBP was the only gene selected by multivariate analyses of both test sets. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Elevated expression of cyclooxygenase-2 is a negative prognostic factor for overall survival in intrahepatic cholangiocarcinoma

2006 ◽  
Vol 450 (2) ◽  
pp. 135-141 ◽  
Author(s):  
Klaus Jürgen Schmitz ◽  
Hauke Lang ◽  
Jeremias Wohlschlaeger ◽  
Henning Reis ◽  
Georgios Charalambos Sotiropoulos ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Intrahepatic Cholangiocarcinoma ◽  
Cyclooxygenase 2 ◽  
Negative Prognostic Factor ◽  
Elevated Expression

scholarly journals DNA Methylation of FKBP5 as Predictor of Overall Survival in Malignant Pleural Mesothelioma

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3470
Author(s):  
Giovanni Cugliari ◽  
Chiara Catalano ◽  
Simonetta Guarrera ◽  
Alessandra Allione ◽  
Elisabetta Casalone ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Overall Survival ◽  
Malignant Pleural Mesothelioma ◽  
P Value ◽  
Pleural Mesothelioma ◽  
Lymphocyte To Monocyte Ratio ◽  
High Incidence ◽  
Aggressive Tumor ◽  
Independent Marker ◽  
The Relationship

Malignant pleural mesothelioma (MPM) is an aggressive tumor with median survival of 12 months and limited effective treatments. The scope of this study was to study the relationship between blood DNA methylation (DNAm) and overall survival (OS) aiming at a noninvasive prognostic test. We investigated a cohort of 159 incident asbestos exposed MPM cases enrolled in an Italian area with high incidence of mesothelioma. Considering 12 months as a cut-off for OS, epigenome-wide association study (EWAS) revealed statistically significant (p value = 7.7 × 10−9) OS-related differential methylation of a single-CpG (cg03546163), located in the 5′UTR region of the FKBP5 gene. This is an independent marker of prognosis in MPM patients with a better performance than traditional inflammation-based scores such as lymphocyte-to-monocyte ratio (LMR). Cases with DNAm < 0.45 at the cg03546163 had significantly poor survival compared with those showing DNAm ≥ 0.45 (mean: 243 versus 534 days; p value< 0.001). Epigenetic changes at the FKBP5 gene were robustly associated with OS in MPM cases. Our results showed that blood DNA methylation levels could be promising and dynamic prognostic biomarkers in MPM.

Microsatellite instability and mutations in BRAF and KRAS in small bowel adenocarcinoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15037-e15037
Author(s):  
Vasiliki Michalaki ◽  
Andreas Polydorou ◽  
Theodosios Theodosopoulos ◽  
George Frangulidis ◽  
Nikolaos Dafnios ◽  
...  
Keyword(s):  
Overall Survival ◽  
Small Bowel ◽  
Microsatellite Instability ◽  
Small Bowel Adenocarcinoma ◽  
Targeted Agents ◽  
First Line ◽  
Braf Mutations ◽  
Platinum Based Chemotherapy ◽  
Molecular Targeted Agents ◽  
Line Chemotherapy

e15037 Background: Small-bowel adenocarcinomas (SBAs) are rare cancers with a significantly lower incidence, later stage at diagnosis, and worse overall survival than other intestinal-derived cancers. Activating KRAS and/or BRAF mutations have been identified as predictors of resistance to anti-epidermal growth factor receptor (EGFR) The aim of this study was to perform a comprehensive immunohistochemical.analysis of KRAS, NRAS, V600E BRAF mutations and microsatellite instability using a cohort of surgically resected cases in our institution. Methods: A total of 17 patients (10 males and 7 females; mean age, 56.2 years old; range, 45-75 years old) received chemotherapy due to non-curative tumor resection, unresectable tumor or post-operative recurrence. Twelve patents received fluoropirimidine and oxaliplatin based first line chemotherapy. Molecular targeted agents were administered to 15 patients, for whom it was their first- or second-line therapy. Results: KRAS mutations were found in 7 cases (41%), out of which 5 (29%) were in exons 12/13. BRAFV600E mutation was observed in 1/17 pt. Microsatellite instability was identified in 3/17pt (MSI; 18%), mainly related to a loss of expression of MLH1 protein. Univariate analysis revealed a PS of 0 (P=0.0226) and treatment with platinum-based chemotherapy (P=0.0047) were significant factors for an improved prognosis. Among the 12 patients who received oxaliplatin-based chemotherapy as a first-line chemotherapy, a PS of 0 (P=0.0255) and treatment with anti-EGFR agents (P=0.0127) were significant positive prognostic factors. Toxicities due to the molecular targeted agents were not experienced. The median overall survival time was 14.3 months (range, 3-52 months), the median DFS was 14.2 months and the median OS was 32 months. Conclusions: To date, there is no standard chemotherapy regimen for advanced SBAs and little is known about their molecular characteristics. The results of the present study indicate that oxaliplatin based chemotherapy containing molecular targeted agents is a well-tolerated and effective treatment option for SBA. A better understanding of disease biology may help to identify therapeutic targets and advance precision medicine.

scholarly journals Brain Metastases in Elderly Patients—The Role of Surgery in the Context of Systemic Treatment

2021 ◽  
Vol 11 (1) ◽  
pp. 123
Author(s):  
Martin Proescholdt ◽  
Stephanie T. Jünger ◽  
Petra Schödel ◽  
Karl-Michael Schebesch ◽  
Christian Doenitz ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factor ◽  
Elderly Patients ◽  
Brain Metastases ◽  
Systemic Treatment ◽  
Karnofsky Performance Status ◽  
Postoperative Treatment ◽  
Negative Prognostic Factor ◽  
Treatment Structure ◽  
The Impact

In patients with brain metastases (BM), advanced age is considered a negative prognostic factor. To address the potential reasons for that, we assessed 807 patients who had undergone BM resection; 315 patients aged at least 65 years (group A) were compared with 492 younger patients (group B). We analyzed the impact of the pre- and postoperative Karnofsky performance status (KPS), postoperative treatment structure and post-treatment survival. BM resection significantly improved KPS scores in both groups (p = 0.0001). Median survival after BM resection differed significantly between the groups (A: 5.81 vs. B: 8.12 months; p = 0.0015). In both groups, patients who received postoperative systemic treatment showed significantly longer overall survival (p = 0.00001). However, elderly patients less frequently received systemic treatment (p = 0.0001) and the subgroup of elderly patients receiving such therapies had a significantly higher postsurgical KPS score (p = 0.0007). In all patients receiving systemic treatment, age was no longer a negative prognostic factor. Resection of BM improves the functional status of elderly patients, thus enhancing the likeliness to receive systemic treatment, which, in turn, leads to longer overall survival. In the context of such a treatment structure, age alone is no longer a prognostic factor for survival.

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