Impact of clinical and molecular features on risk of recurrence following curative intent resection of metastases in metastatic colorectal cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 785-785
Author(s):  
Matthew E. Burge ◽  
Belinda Lee ◽  
Margaret Lee ◽  
Rachel Wong ◽  
Phillip Parente ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Primary Tumour ◽  
Clinical Predictors ◽  
Curative Intent ◽  
Mutation Status ◽  
Molecular Features ◽  
Kaplan Meier ◽  
Resection Of Metastases ◽  
Primary 76

785 Background: Resection of metastases with curative intent is an integral component of mCRC management. However, relapse rates are high and identifying patients most likely to benefit from this approach is of considerable importance. Among patients with mCRC, mutations (mt) in RAS and BRAF genes portent a worse prognosis. Our hypothesis, therefore, is that patients harbouring these mutations may have a higher relapse rate after resection of metastases. We also wished to analyse clinical predictors of relapse, including site of metastases. Methods: We interrogated the TRACC database of patients undergoing resection with curative intent who had mutation status available. The frequency of RAS and BRAF mt was established and their association with clinical parameters determined. Relapse free (RFS) and overall survival (OS), from the date of resection, was estimated for the mt and wild type (wt) groups using the Kaplan Meier method. Multivariate analysis is planned to investigate factors associated with RFS, including stage of the primary tumour, synchronous metastases, site and number of metastases, CEA, peri-operative chemotherapy use, site of the primary (left v right) and RAS and BRAF mutation status. Results: 188 patients were identified. 89 were KRAS/BRAF wt, 92 KRAS mt and 7 BRAF mt. 40% had presented with metastatic disease and 27% had a right sided primary. 76%, 22% and 2% underwent resection of liver, lung or both metastases. Microscopic resection margin was involved in 6%. Resection was performed prior to any chemotherapy in 48%. No difference was seen in relapse free or overall survival between the mt and wt groups. Conclusions: We found no difference in relapse free or overall survival by mutation subgroup suggesting this should not influence suitability for curative intent resection, but analyses is planned on a much larger cohort once data is available. A multivariate analysis, adjusting for important prognostic variables, is planned.

EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing's sarcoma.

1998 ◽  
Vol 16 (4) ◽  
pp. 1248-1255 ◽  
Author(s):  
E de Alava ◽  
A Kawai ◽  
J H Healey ◽  
I Fligman ◽  
P A Meyers ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Molecular Heterogeneity ◽  
Curative Intent ◽  
Adequate Treatment ◽  
Fusion Transcripts ◽  
Fusion Type

PURPOSE More than 90% of Ewing's sarcomas (ES) contain a fusion of the EWS and FLI1 genes, due to the t(11;22)(q24;q12) translocation. At the molecular level, the EWS-FLI1 rearrangements show great diversity. Specifically, many different combinations of exons from EWS and FLI1 encode in-frame fusion transcripts and result in differences in the length and composition of the chimeric protein, which functions as an oncogenic aberrant transcription factor. In the most common fusion type (type 1), EWS exon 7 is linked in frame with exon 6 of FLI1. As the fundamental pathogenetic lesion in ES, the molecular heterogeneity of these fusion transcripts may have functional and clinical significance. PATIENTS AND METHODS We performed a clinical and pathologic analysis of 112 patients with ES in which EWS-FLI1 fusion transcripts were identified by reverse-transcriptase polymerase chain reaction (RT-PCR). Adequate treatment and follow-up data were available in 99 patients treated with curative intent. Median follow-up in these 99 patients was 26 months (range, 1 to 140 months). Univariate and multivariate survival analyses were performed that included other prognostic factors, such as age, tumor location, size, and stage. RESULTS Among the 99 patients suitable for survival analysis, the tumors in 64 patients contained the type 1 fusion and in 35 patients contained less common fusion types. Stage at presentation was localized in 74 patients and metastatic in 25. Metastases (relative risk [RR] = 2.6; P = .008), and type 1 EWS-FLI1 fusion (RR = 0.37; P = .014) were, respectively, independent negative and positive prognostic factors for overall survival by multivariate analysis. Among 74 patients with localized tumors, the type 1 EWS-FLI1 fusion was also a significant positive predictor of overall survival (RR = 0.32; P = .034) by multivariate analysis. CONCLUSION EWS-FLI1 fusion type appears to be prognostically relevant in ES, independent of tumor site, stage, and size. Further studies are needed to clarify the biologic basis of this phenomenon.

Homozygous Deletion of p16, p14 and p15 Is a Poor Prognostic Factor in Adult B-Lineage Acute Lymphoblastic Leukemia, Not in Childhood B-ALL: A Comparison through Deletion and Hypermethylation Study

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4477-4477
Author(s):  
Miyoung Kim ◽  
Seon-Hee Yim ◽  
Hai Rim Shin ◽  
Nam Sun Cho ◽  
Seong_Ho Kang ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Promoter Methylation ◽  
Lymphoblastic Leukemia ◽  
Disease Free Survival ◽  
Homozygous Deletion ◽  
P Value ◽  
Free Survival ◽  
Kaplan Meier ◽  
P15 Gene

Abstract Backgrounds: The biologic characteristics of childhood acute lymphoblastic leukemia (ALL) is different from those of adult ALL. Tumor suppressor genes, p16, p14, and p15 gene are inactivated either by promoter methylation, deletion or mutation, however, in leukemia, promoter methylation and deletion are the main mechanisms of inactivation. Aims: To compare the alteration status of p16, p14, and p15 gene in childhood and adult ALL, we analyzed the incidences and the prognostic significances of deletion and hypermethylation of p16, p14, and p15 in childhood and adult B-ALL. The association between alterations of those genes and known cytogenetic prognostic factors (BCR-ABL, TEL-AML, MLL rearrangement, and numerical changes) were also assessed. Methods: A total of 91 newly diagnosed B-ALL patients (61 children, 30 adults) were studied. Interphase fluorescent in situ hybridization study (p16, BCR-ABL, TEL-AML, MLL) and methylation specific PCR were performed using bone marrow mononuclear cells. Numerical changes were assessed by FISH and chromosome analysis. Chi-square test, Fisher’s exact test, Kaplan and Meier method and Cox proportional hazards regression were applied for statistical analysis. Results: The frequencies of homozygous deletion of p16, p14, and p15 were 11.5% in children and 30.0% in adult, showing higher incidence in adults (p=0.029). In overall survival study, homozygous deletion was associated with the worse prognosis in adults (Fig 1, p=0.019), but not in childhood. The incidences of promoter methylation of p16, p14, and p15 were as follows: 34.4%, 14.8%, and 34.4% in children; 26.7%, 10.0%, and 40.0% 26.7% in adults, respectively, with no statistical difference between two groups. No significant association was observed between deletion and hypermethylation. Childhood ALL showed inactivation of p16 (39.3%), p14 (24.6%), and p15 (42.6%), while adult ALL showed inactivation of p16 (46.7%), p14 (33.3%), and p15 (56.7%), with the same order of frequencies, but with higher tendency of methylation in adult ALL. In p14 unmethylated adults, the homozygous deletion had adverse effect on overall survival (OS) (p=0.036). There were no significant association between chromosomal aberrations and promoter methylation in childhood and adult ALL. The children with sole MLL rearrangement showed poorer disease free survival (DFS) than those with sole homozygous deletion with low statistical significance (p=0.059). Homozygous deletion was translated into poor prognosis in OS in adults without MLL rearrangement (p=0.011). Adult with normal karyotype showed shorter OS when accompanied by homozygous deletion, although p value was 0.051. Conclusions: We performed a comprehensive analysis of deletion and hypermethylation of p16, p14, and p15 genes in both childhood and adult B-ALL. Homozygous deletion was more frequent in adults, showing association with shorter OS in adults, but not in children. This difference of distribution and prognostic value between childhood and adult ALL could be one of the explanations for the disparity of clinical outcome. Our results suggest that homozygous deletion is an independent prognostic factor in adult ALL. Table 1. Deletion and methylation profiles of p16, p14, and p15, and their prognostic siginificances P16, P14, and P15 Deletion P16 Methylation P14 Methylation P15 Methylation *P: p value by multivariate analysis †OS: Overall survival ‡DPS: Disease free survival Childhood Frequency 11.5% 34.4% 14.8% 34.4% *P (†OS) 0.853 0.979 0.651 0.591 P (‡DPS) 0.716 0.956 0.809 0.977 Adults Frequency 30.0% 26.7% 10.0% 40.0% P (OS) 0.019 0.151 0 892 0.330 P (DPS) 0.218 0.382 0.079 0.760 Figure 1. Kaplan-Meier curve for childhood and adult B-ALL patients.
 P value was obtained by multivariate analysis using Cox hazard regression model. (A) Childhood B-ALL (B) B. Adult B-ALL Figure 1. Kaplan-Meier curve for childhood and adult B-ALL patients.
 P value was obtained by multivariate analysis using Cox hazard regression model. (A) Childhood B-ALL (B) B. Adult B-ALL

Sites of Extranodal Involvement Are Prognostic in Patients with Stage 1 Follicular Lymphoma: An Analysis of the Surveillance, Epidemiology and End Results Database

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1670-1670
Author(s):  
Aditi Shastri ◽  
Yiting Yu ◽  
Amit Verma ◽  
Stefan Klaus Barta
Keyword(s):  
Overall Survival ◽  
Nervous System ◽  
Multivariate Analysis ◽  
Lymph Node ◽  
Musculoskeletal System ◽  
Primary Site ◽  
Stage I ◽  
Aggressive Treatment ◽  
Primary Disease ◽  
Kaplan Meier

Abstract Background: Follicular lymphoma (FL) is the most common indolent B cell lymphoma with a rising incidence. Approximately 26% of patients with FL present with stage I disease. Although international consensus guidelines recommend radiotherapy for these patients, a recent survey of the National Lymphocare Study demonstrated that adherence to the standard is low with less than one third of patients treated with radiotherapy, whereas the rest were only observed, received single-agent rituximab, or a combination of rituximab with chemotherapy +/- subsequent radiotherapy. There is evidence to suggest that extranodal sites of involvement are associated with better/worse outcomes in other lymphomas (DLBCL, MCL). Hence, we examined the association between primary site of disease and survival in patients with Stage I FL to identify subgroups of patients that have distinct characteristics and could potentially benefit from early and/or more aggressive treatment. Methods: We analyzed the United States SEER database from 1983 to 2011. Direct case listings were extracted by SEER*Stat software, version 8.1.5, released March 31,2014. All histologically confirmed, Stage I FL cases, age > 18 years, with active follow-up and only a single primary tumor were included in the analysis. Overall survival (OS) estimates for each primary site were calculated using the Kaplan-Meier method and log rank test. We assessed the impact of primary disease site on OS using Cox proportional hazards models adjusted for age, sex, race, radiotherapy, surgery and era of diagnosis (pre-rituximab era: Õ83-Õ98 vs. rituximab era: Õ99-Õ11). Calculations were performed using SAS, version 9.3. Results: We analyzed 9931 total patients, 25% of patients presented with an extranodal primary site. The most common extranodal primary sites were the integumentary system (8%), GI tract (6.4%) and the head & neck region (5.6%). In univariate analysis, Stage I FL of the integumentary system was associated with better OS than lymph node (LN) primary disease (HR 0.74, 95% CI 0.63 to 0.59). Primary site FL of the respiratory system (HR 1.69, CI 1.18 to 2.4), musculoskeletal system (HR 2, CI 1.37 to 3) and nervous system (HR 1.9, CI 1.37 to 2.68) were significantly associated with worse overall survival than lymph node primary disease. In multivariate analysis, only integumentary disease was associated with better OS (HR 0.77, CI 0.66 to 0.9) while primary site FL of the nervous system (HR 2.4, CI 1.72 to 3.38) and the musculoskeletal system (HR 2.14, CI 1.44 to 3.18) were associated with worse overall survival than lymph node primary disease. Patients treated in the rituximab era had a better OS on multivariate analysis than if treated in the pre-rituximab era (p<0.0001). Female sex was associated with better survival while older age at diagnosis was associated with worse survival (p<0.0001). In multivariate analysis, patients who received surgery or radiation had better survival than those that did not receive any therapy and Whites had better survival than Blacks (both p<0.0001). Conclusions: Primary site of disease may be an important prognostic factor for patients with early stage FL as demonstrated by this population-based study. Patients with Stage I FL of the integumentary system had a significantly better outcome than primary nodal disease. Musculoskeletal and nervous system primary sites had a significantly worse survival than primary nodal sites. These subsets of patients may benefit from early, aggressive treatment. Primary site may correlate with certain biological characteristics associated with disease behavior and pathogenesis and needs further evaluation. Overall survival was significantly better in the rituximab era. Figure 1. Kaplan Meier Curve demonstrating OS of integumentary system vs. lymph node primary site (180 months vs. 170 months, p <0.0001), nervous system vs. lymph node primary site (95 months vs. 170 months, p <0.0001) and musculoskeletal system vs. lymph node primary site (96 months vs. 170 months, p <0.0001). Figure 1. Kaplan Meier Curve demonstrating OS of integumentary system vs. lymph node primary site (180 months vs. 170 months, p <0.0001), nervous system vs. lymph node primary site (95 months vs. 170 months, p <0.0001) and musculoskeletal system vs. lymph node primary site (96 months vs. 170 months, p <0.0001). Disclosures No relevant conflicts of interest to declare.

Complete Remissions (CRs) with Azacitidine Regimens Compared to Crs with 7+3 Induction Chemotherapy and the Effect on Overall Survival

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1613-1613 ◽  
Author(s):  
Megan Othus ◽  
Mikkael A Sekeres ◽  
Sucha Nand ◽  
Guillermo Garcia-Manero ◽  
Frederick R. Appelbaum ◽  
...  
Keyword(s):  
Overall Survival ◽  
Prognostic Factors ◽  
Research Funding ◽  
Cox Regression ◽  
Intensive Therapy ◽  
Univariate Analysis ◽  
Multivariable Analysis ◽  
Curative Intent ◽  
Kaplan Meier ◽  
The Impact

Abstract Background: CR and CR with incomplete count recovery (CRi) are associated with prolonged overall survival (OS) for acute myeloid leukemia (AML) patients (pts) treated with curative-intent, induction therapy. For AML pts treated with azacitidine (AZA), response (CR, partial response, marrow CR, or hematologic improvement) is also associated with prolonged OS. We evaluate whether patients given AZA for myelodysplastic syndromes (MDS) or AML had longer OS if they achieved CR. We also compare the effect size of CR on OS between AZA regimens and 7+3. Patients and Methods: We analyzed four SWOG studies: S1117 (n=277) was a randomized Phase II study comparing AZA to AZA+lenalidomide or AZA+vorinostat for higher-risk MDS and CMML pts (median age 70 years, range 28-93); S0703 (n=133) treated AML pts not eligible for curative-intent therapy with AZA+mylotarg (median age 73 years, range 60-88). We analyzed the 7+3 arms of S0106 (n=301 were randomized to 7+3, median age 48 years, range 18-60) and S1203 (n=261 were randomized to 7+3, median age 48 years, range 19-60). CR was defined per 2003 International Working Group criteria. In S1117 CR was assessed every 16 weeks and patients remained on therapy until disease progression. In S0703, S0106, and S1203 CR was assessed following 1-2 induction cycles; patients not achieving CR (S0106) or CRi (S0703 and S1203) were removed from protocol treatment. OS was measured from date of study registration. To avoid survival by response bias, we performed landmark analyses of OS. We present results based on the study-specific landmark date that 75% of pts who eventually achieved a CR had done so (S1117 144 days, S0703 42 days, S0106 44 days, S1203 34 days). Pts who did not achieve CR by this date were analyzed with pts who never achieved CR. Pts who died or were lost to follow-up before this date were excluded from analyses. As a sensitivity analysis we also analyzed based on the 90% date; results were not materially different. Log-rank tests were used to compare survival curves and Cox regression models were used for multivariable modeling including baseline prognostic factors age, sex, performance status, white blood cell count, platelet count, marrow blast percentage, de novo disease (versus antecedent MDS or therapy-related disease), study arm (for S1117 only), and cytogenetic risk (IPSS criteria for S1117, SWOG criteria for S0703, S0106, and S1203). The following analysis considers morphologic CR only. S0106 treated CR with incomplete count recover (CRi) pts as treatment failures (S0703 and S1203 did not) and CRi was not defined for S1117. Hematologic improvement was only defined for S1117 patients. Results: In univariate analysis, CR was significantly associated with prolonged survival among MDS pts treated with azactidine on S1117 (HR=0.55, p=0.017), confirming the results seen in AML pts treated with azacitidine (and mylotarg, S0703, HR=0.60, p=0.054) and 7+3 (S0106 HR=0.44, p<0.001; S1203 HR=0.32, p<0.0001) (Figure 1). For each study this relationship remained significant in multivariable analysis controlling for baseline prognostic factors (S1117 HR=0.25, p<0.001; S0703 HR=0.64, p=0.049; S0106 HR=0.45, p<0.001; S1203 HR=0.41, p<0.001). There was no evidence that the impact of CR varied across the four cohorts (interaction p-value = 0.76). In the full cohort, the effect of CR was associated with a HR of 0.45 (Table 1). Conclusion: Adjusting for pt characteristics, achievement of morphologic CR was associated with a 60% improvement in OS, on average, compared to that seen in pts who don't achieve a CR, regardless of whether pts were treated with 7+3 or AZA containing regimens, and suggesting that value CR is similar of whether pts receive more or less "intensive" therapy for these high grade neoplasms. Support: NIH/NCI grants CA180888 and CA180819 Acknowledgment: The authors wish to gratefully acknowledge the important contributions of the late Dr. Stephen H. Petersdorf to SWOG and to study S0106. Figure 1 Kaplan-Meier plots of landmark survival by response. Figure 1. Kaplan-Meier plots of landmark survival by response. Table 1 Multivariable analysis, N=878 Table 1. Multivariable analysis, N=878 Disclosures Othus: Glycomimetics: Consultancy; Celgene: Consultancy. Sekeres:Celgene: Membership on an entity's Board of Directors or advisory committees. Erba:Millennium Pharmaceuticals, Inc.: Research Funding; Amgen: Consultancy, Research Funding; Seattle Genetics: Consultancy, Research Funding; Agios: Research Funding; Gylcomimetics: Other: DSMB; Juno: Research Funding; Daiichi Sankyo: Consultancy; Sunesis: Consultancy; Pfizer: Consultancy; Ariad: Consultancy; Jannsen: Consultancy, Research Funding; Incyte: Consultancy, DSMB, Speakers Bureau; Celator: Research Funding; Astellas: Research Funding; Celgene: Consultancy, Speakers Bureau; Novartis: Consultancy, Speakers Bureau.

Association of mucin production and survival in colon cancer.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 512-512 ◽  
Author(s):  
John Hogan ◽  
Georges Samaha ◽  
John Burke ◽  
David Waldron ◽  
Eoin Condon ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Free Survival ◽  
Mucin Production ◽  
Kaplan Meier ◽  
The Relationship ◽  
Disease Free

512 Background: Debate persists regarding the relationship between mucin production and cancer-related outcome following curative resection for colon cancer. Lack of consensus is due to (amongst other factors) discrepancies in definition, small cohort studies and the integration of both colon and rectal cancers. This study characterizes the relationship between mucin production and cancer-related outcome in an homogenous single-institute based cohort. Methods: A database spanning demographics, clinico-pathologic characteristics and prognostic factors was generated for all patients undergoing curative-intent colonic resection in the interval 2000 to 2010. Patients were categorized simply as mucin producing (i.e. MC) or non-mucin producing adenocarcinoma (NMC). Primary outcomes included overall survival (time to death from any cause) and disease free survival (time to loco-regional and systemic recurrence). Trends were established for MC and NMC using Kaplan-Meier estimates, plotted and compared using log-rank analysis. Findings significant on univariate analysis were incorporated into multivariate analysis. Cox proportional hazards model was employed to determine the associated hazard of both death and disease recurrence in each group. Statistical analysis was performed using R version 2.15. P < 0.05 was considered significant. Results: 77 mucinous carcinomas (MC) and 358 non mucinous carcinomas (NMC) were included. On univariate analysis, MC was associated with improved overall survival (OS) (P=0.007). Both N1 (HR 1.625, P=0.011) and N2 (HR 2.7, P<0.001) status were associated with adverse OS. On multivariate analysis, MC approached but did not reach statistical significance for improved OS (HR 0.543, P=0.061). A comparison of Kaplan-Meier estimates for overall survival in MC and NMC groups indicated that OS was significantly improved in the MC cohort (P=0.011). There was no difference in disease free survival (P=0.224). Systemic recurrence was greater in the NMC group (P=0.042). Conclusions: Mucin production in colonic adenocarcinoma appears associated with improved overall but not disease-free survival. In addition, the absence of mucin was associated with adverse systemic but not local recurrence.

Meat consumption and BRAF mutation status in colorectal cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e15135-e15135
Author(s):  
Rosa L. Frias ◽  
Michael Lam ◽  
Michael J. Overman ◽  
Van K. Morris ◽  
David R. Fogelman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Logistic Regression ◽  
Meat Consumption ◽  
Braf V600e Mutation ◽  
Braf V600e ◽  
P Value ◽  
Mutation Status ◽  
Molecular Features ◽  
Total Meat

e15135 Background: Consumption of red and processed meat has been associated with increased risk of developing colorectal cancers, but less is known about the association of meat consumption with tumor molecular features. In this study, we tested the association of total meat consumption with molecular features of colorectal cancer and overall survival in a local cohort of patients. Methods: Data on meat consumption were collected using self-directed environmental surveys from patients with stage IV/locally advanced, treatment refractory colorectal cancer who were enrolled on the Assessment of Targeted Therapies Against Colorectal Cancer clinical protocol. Data on tumor molecular features were collected through medical record review. Patients were categorized into low, medium or high meat consumption groups based on servings per day tertile. Associations between tumor molecular features and meat intake were evaluated by Chi-square and logistic regression. Potential effects of meat consumption on overall survival were assessed using Cox Proportional Hazards models. Analyses were conducted with IBM SPSS v25. Results: Patients consumed an average of 0.74, 1.57 and 3.32 servings of meat per day in the low, medium and high categories, respectively. Out of 593 patients with evaluable data, 27 were found to have a BRAF V600E mutation. Total meat consumption differed significantly by BRAF V600E mutation status (p value 0.02) and by sex (p value < .01), but did not differ by tumor location, microsatellite instability, or RAS mutation status. Using logistic regression, we found that compared to patients with the highest level of meat consumption, those in the medium consumption group may be less likely to have a BRAF V600E mutation (OR 0.24; p value 0.08). Although meat consumption may be associated with BRAF mutation status, it was not predictive of overall survival in our analyses. Conclusions: Among patients in our study, meat consumption may be associated with tumor BRAF V600E mutation status but is not directly associated with survival. Additional work is needed to test this association in cohorts including more BRAF mutant cases. If confirmed, this finding may add further insight into the etiology and biology of these tumors.

Univariate and Multivariate Analysis of Prognostic Factors in the Surgical Treatment of Hilar Cholangiocarcinoma

2010 ◽  
Vol 76 (11) ◽  
pp. 1260-1268 ◽  
Author(s):  
Giovanni Ramacciato ◽  
Giuseppe Nigri ◽  
Riccardo Bellagamba ◽  
Niccolò Petrucciani ◽  
Matteo Ravaioli ◽  
...  
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Prognostic Factors ◽  
Hilar Cholangiocarcinoma ◽  
R0 Resection ◽  
Safe Procedure ◽  
Tumor Grading ◽  
Curative Intent ◽  
Aggressive Surgical Approach ◽  
Well Differentiated

Surgery is the only effective treatment able to improve survival of patients with hilar cholangiocarcinoma (CCA). However, the significance of prognostic factors on overall survival is still debated. We evaluated early and long-term outcomes of patients resected for hilar cholangiocarcinoma over a 3-year period to determine the role of prognostic factors and their effect on overall survival. Medical records of patients with hilar CCA who underwent resection between January 2001 and December 2004 were retrospectively reviewed. Univariate and multivariate analysis was performed to identify prognostic factors associated with survival. Thirty-two of 45 patients underwent surgical resection with curative intent. Morbidity was 24.4 per cent; perioperative mortality was 0 per cent. Overall median survival was 22.3 months. Well-differentiated tumor grading and R0 resection were independently associated with better survival at multivariate analysis. Aggressive surgery, including biliary resection combined with major hepatectomy, is a safe procedure with low morbidity and mortality in a tertiary referral hepatobiliary center. The main aim of an aggressive surgical approach is to obtain a microscopic margin-negative resection, which is associated with better prognosis. Another important prognostic factor is tumor grading, which is independently associated with survival.

scholarly journals Expression of TCF7L2 in Glioma and Relation With Clinicopathological Characteristics and Patient Overall Survival

2020 ◽  
Author(s):  
S.-Y. JING ◽  
L. CHEN ◽  
S. HAN ◽  
N. LIU ◽  
M.-Y. HAN ◽  
...  
Keyword(s):  
Overall Survival ◽  
Transcription Factor ◽  
Multivariate Analysis ◽  
Prognostic Factor ◽  
Clinicopathological Characteristics ◽  
Low Grade Glioma ◽  
Independent Prognostic Factor ◽  
Low Grade ◽  
Kaplan Meier ◽  
The Relationship

Abstract Background: TCF7L2 gene is known as transcription factor 7-like 2 which has been identified as a novel transcription factor epithelial-mesenchymal transition (EMT) in tumor cells at 10q25.3. TCF7L2 may affect cancer progression and plays a central role in cancer proliferation, migration and invasion. However, its clinical and prognostic value have not been researched in glioma. The purpose of our study was to research TCF7L2 expression and evaluate the clinical value of prognosis.Method: We collected glioma specimens including low-grade glioma (n=46)and glioblastoma (n=51) from September 2015 to September 2017.Expression of TCF7L2 in 97 specimens were detected by quantitative real-time PCR (qRT-PCR).The chi-square test was applied to analyze the relationship between TCF7L2 expression and clinicopathological characteristics. The overall survival (OS) was analyzed by binary logistic regression analysis, the survival curves were drew by Kaplan-Meier. Univariate and multivariate analysis were utilized to analyze the relationship between prognosis and clinicopathological characteristics including TCF7L2 expression.RESULTS: Compared with low-grade glioma group, the expression of TCF7L2 was significantly increased (p<0.05). TCF7L2 overexpression was associated with large tumor volume (p=0.03), higher WHO grade (p=0.001), and recurrence (p=0.001). Moreover, Kaplan-Meier analysis proved that overexpressed TCF7L2 was related with poor OS (p< 0.05).The multivariate analysis suggested that TCF7L2 expression was an independent prognostic factor.CONCLUSIONS: Our research proved that TCF7L2 was over- expressed in glioblastoma, and, related with tumor prognosis, which, therefore, could be an independent prognostic factor for glioma patients.

scholarly journals Expression of TCF7L2 in Glioma and Its Relationship With Clinicopathological Characteristics and Patient Overall Survival

2021 ◽  
Vol 12 ◽  
Author(s):  
Shiyuan Jing ◽  
Lei Chen ◽  
Song Han ◽  
Ning Liu ◽  
MingYang Han ◽  
...  
Keyword(s):  
Overall Survival ◽  
Transcription Factor ◽  
Multivariate Analysis ◽  
Prognostic Factor ◽  
Clinicopathological Characteristics ◽  
Low Grade Glioma ◽  
Independent Prognostic Factor ◽  
Low Grade ◽  
Kaplan Meier ◽  
The Relationship

Background: The TCF7L2 gene is known as transcription factor 7-like 2 which has been identified as a novel transcription factor epithelial-mesenchymal transition (EMT) in tumor cells at 10q25.3. TCF7L2 may affect cancer progression and plays a central role in cancer proliferation, migration, and invasion. However, its clinical and prognostic value have not been researched in glioma. The purpose of our study was to research TCF7L2 expression and evaluate the clinical value of prognosis.Method: We collected glioma specimens including low-grade glioma (n = 46) and glioblastoma (n = 51) from September 2015 to September 2017. Expression of TCF7L2 in 97 specimens was detected by quantitative real-time PCR (qRT-PCR). The chi-square test was applied to analyze the relationship between TCF7L2 expression and clinicopathological characteristics. The overall survival (OS) was estimated by log-rank tests among strata, and the survival curves were drawn by Kaplan-Meier. Univariate and multivariate analysis were utilized to analyze the relationship between prognosis and clinicopathological characteristics including TCF7L2 expression.Results: Compared with the low-grade glioma group, the expression of TCF7L2 was significantly increased in the glioblastoma group (p = 0.001). TCF7L2 overexpression was associated with higher WHO grade (p = 0.001), isocitrate dehydrogenase (IDH) wild-type (p = 0.001), and lack of O(6)-methylguanine-DNA methyltransferase (MGMT) methylation (p = 0.001). Moreover, Kaplan-Meier analysis proved that overexpressed TCF7L2 was associated with poor OS (p = 0.010). The multivariate analysis suggested that TCF7L2 expression was an independent prognostic factor (p = 0.020).Conclusions: Our research proved that TCF7L2 was overexpressed in glioblastoma, and related with tumor long-term prognosis, which, therefore, could be an independent prognostic factor for glioma patients.

scholarly journals Prognostic Impact of Subclonal TP53 Aberrations in Chronic Lymphocytic Leukemia Validated By a Robust Targeted Next Generation Sequencing Assay

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4380-4380
Author(s):  
Christian Brieghel ◽  
Christina Westmose Yde ◽  
Caspar da Cunha-Bang ◽  
Savvas Kinalis ◽  
Lone Bredo Pedersen ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lymphocytic Leukemia ◽  
Prognostic Impact ◽  
Mutation Status ◽  
Tp53 Mutations ◽  
Targeted Next Generation Sequencing ◽  
Kaplan Meier ◽  
Significant Difference ◽  
Generation Sequencing ◽  
Allelic Burden

Abstract Introduction/background: Clonal TP53 aberrations (del(17p) and/or TP53 mutations) in patients with chronic lymphocytic leukemia (CLL) correlates with a poor prognosis. Similar outcome has been demonstrated for patients with subclonal TP53 aberrations (Rossi, Blood, 2014). In order to guide novel targeted therapies approved in frontline treatment of TP53 aberrated (TP53+) CLL, development and clinical validation of robust assays for subclonal TP53 aberrations is warranted. Methods: DNA extracted from peripheral blood of CLL patients were diluted 1:5 in DNA derived from a cell line containing a known, but rare TP53 point mutation. TP53 exons 2-10 were PCR amplified from undiluted and diluted DNA in parallel using Phusion proofreading DNA polymerase and subsequently sequenced by targeted Next Generation Sequencing (tNGS) on Illumina MiSeq and HiSeq 2500. Sensitivity and specificity of the assay was tested by serial dilution of patient samples with known TP53 insertions, deletions or substitutions. Consecutive biobanked samples from CLL patients at a single institution were used for validation of the clinical impact of subclonal TP53 aberrations. Nucleotide variants were called by CLC Biomedical Genomics Workbench 3.0. An algorithm for detection of true mutations was developed based on comparison of the diluted and undiluted samples analyzed in parallel. Overall survival (OS) was analyzed using Kaplan-Meier. Results: The sensitivity and specificity of the assay was validated by detection of all 8 known TP53 aberrations in serial dilutions with the threshold of the assay established at 0.2% allelic burden. Known mutations were still detectable at 0.02% at the highest dilution. A test sample of patients with known del(17p) demonstrated TP53 mutations in 6 out of 7 patients (5 clonal and 1 subclonal TP53+) in accordance with previously reported frequencies of TP53 mutations among patients with del(17p). In total, 92 samples from 46 consecutive patients were analyzed. With a median coverage of 93,272 reads (98% above 20,688 reads, range: 5,153-720,025), 27 TP53 aberrations were found in 10 (22%) of the patients. Twenty-six (96%) mutations were subclonal with a median allelic burden of 0.9% (range: 0.2-97.5%). Seven patients had a single aberration. In two previously treated patients, 8 and 10 subclonal aberrations were detected. One patient with a known del(17p) also had subclonal TP53 mutations. Three patients had solely subclonal mutations below 1% allelic burden. Considered the hot spot region of TP53 in CLL, exons 4-8 harbored 93% of the detected mutations. The median (IQR) survival for TP53+ patients and patients with wild type TP53 (wt-TP53) was 37.5 (range: 2-106) and 104 (range: 9-113) months, respectively. In Kaplan-Meier analyses, TP53+ patients had a significantly poorer OS versus patients with wt-TP53 (p=0.00002, Figure 1). The two TP53+ long-term survivors both had an allelic burden below 1%, and the only other TP53+ patient with less than 1% allelic burden survived for 53 months, indicating that the prognostic impact of very low allelic burden TP53 aberrations needs further investigation. Conclusion: We have developed a robust assay for TP53 aberrations with a sensitivity of 0.2% allelic burden based on an algorithm including a dilution step. In an initial test cohort of 46 patients, 10 patients demonstrated TP53 mutations as low as 0.2% allelic burden that significantly affected OS. Validation of the clinical impact of subclonal TP53 aberrations is ongoing based on our consecutive biobank with 600+ patients. Establishment of a new cut-off for clinical treatment decisions based on subclonal TP53 aberrations is warranted. Figure 1 Overall survival in 46 consecutive CLL patients based on TP53 mutation status shows significant difference (p=0.00002) between patients withwild type TP53 (wt-TP53) and TP53 mutations (TP53+) as low as 0.2% allelic burden. Figure 1. Overall survival in 46 consecutive CLL patients based on TP53 mutation status shows significant difference (p=0.00002) between patients withwild type TP53 (wt-TP53) and TP53 mutations (TP53+) as low as 0.2% allelic burden. Disclosures Niemann: Gilead: Consultancy; Abbvie: Consultancy; Roche: Consultancy; Janssen: Consultancy.

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