Sequencing of treatment matters in synchronous liver or lung only metastatic colon cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4049-4049
Author(s):  
Saurabh Parasramka ◽  
Aasems Jacob ◽  
Quan Chen ◽  
Bin Huang ◽  
Zhonglin Hao
Keyword(s):  
Colon Cancer ◽  
Multivariate Analysis ◽  
Metastatic Disease ◽  
Proportional Hazards ◽  
Private Insurance ◽  
Univariate Analysis ◽  
Academic Research ◽  
Metastatic Colon Cancer ◽  
Sensitive Analysis ◽  
Additional Surgery

4049 Background: Per SEER database, approximately 21% of patients have synchronous metastatic disease at presentation with a median 5 year survival of 14%. Liver is by far the most common site of metastatic disease followed by lung. Metastatectomy of appropriate lesions have achieved a 5 year survival ranged between 40%-70% depending on the extent of the metastasis. For liver or lung only metastatic disease, practice varies from surgery followed by adjuvant chemotherapy to perioperative chemotherapy. Benefit of one approach versus the other has not been demonstrated. We decided to study this using the National Cancer Database (NCDB) database available from the 2010-2015 period. Methods: Adults > 20 years with primary colon cancer (excluding rectal and recto sigmoid junction) with single organ metastatic disease to liver and/or lung at diagnosis were identified. All patients had received surgery to the primary site, resection of the distant site and chemotherapy in the neoadjuvant setting (NAC) or adjuvant setting (AC) within 1 year of diagnosis. Histology except for adenocarcinoma and variants were excluded. Patients who died within 90 days of surgery were excluded. Descriptive analysis, Kaplan-Meier plots, Log-Rank tests for univariate and proportional hazards models for multivariate survival analyses were performed. To reduce biases, a sensitive analysis was also performed based on the intention to treat principle by including additional surgery only and chemotherapy only cases. Results: A total of 3175 colon cancer patients with liver or lung only metastatic disease were identified. 2487 (78%) had AC and 688 (22%) had NAC. Approximately 54% were males with 90% less than 75 years of age. More patients had private insurance and were treated in academic centers in the NC group (62 Vs 51%) and (58 Vs 42%) respectively. Both groups had similar Charlson comorbidity index. NC approach had better OS with HR of 0.75 (CI 0.65-0.85; p < 0.0001) on univariate analysis and 0.86 (0.74-0.98; P < 0.0281) on multivariate analysis. On multivariate analysis, age group > 75 years, black race, treatment outside academic research program had worse survival (p < 0.0001, 0.0139, 0.0001) respectively. The sensitive analysis showed the similar effects. Conclusions: Within the limitations of database review, our analysis suggests survival advantage of neoadjuvant chemotherapy approach over surgery first.

Neoadjuvant chemotherapy to improve colon cancer survival in resectable metastatic colon cancer: A real world NCDB data analysis.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 3567-3567
Author(s):  
Saurabh Parasramka ◽  
Aasems Jacob ◽  
Quan Chen ◽  
Bin Huang ◽  
Zhonglin Hao
Keyword(s):  
Colon Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Metastatic Disease ◽  
Real World ◽  
Cox Regression ◽  
Survival Advantage ◽  
Metastatic Colon Cancer ◽  
Factors Associated ◽  
Additional Surgery ◽  
Single Organ

3567 Background: According to the SEER database, approximately 21% of colon cancer patients have synchronous metastatic disease at presentation with a five-year survival of only 14%. Liver is by far the most common site of metastasis. For resectable and borderline resectable metastatic lesions after conversion to surgical resection, five-year survival ranges between 40-70% in different series. Survival advantage of neoadjuvant chemotherapy is not clear. We present here an updated analysis of effect of different variables on survival of 3,247 patients from the National Cancer Database (NCDB) treated from 2010-2015. Methods: Adults 20 years or older with primary colon cancer and single organ metastatic disease either in the liver and/or lung at diagnosis were identified. All patients had received surgery to the primary site, resection of the distant site and chemotherapy within 1 year of diagnosis. Patients were categorized into 2 cohorts based on whether they received chemotherapy in the pre-operative/peri-operative setting (neoadjuvant chemotherapy –NAC) or post-operative setting (adjuvant chemotherapy AC). Descriptive analysis, Kaplan-Meier plots, Log-Rank tests and Cox regression models for multivariate survival analyses were performed. To assess uncertainty of estimates, a sensitive analysis was also performed based on the intention to treat principle by including additional surgery only and chemotherapy only cases. Results: A total of 3,247 patients with colon cancer with liver or lung metastases were identified. A large majority 2,527 patients (77.8%) received AC. 54.5% were males and 45.5% females. On multivariate analysis, patients who received NAC had overall survival (OS) advantage with hazard ratio (HR) 0.86 (0.75-0.98). Clinical factors associated with worse survival included age > 75 HR 1.31; positive margin status with R1 HR 1.49 or R2 HR 2.33; Comorbidity index ≥ 2 HR 1.68; positive KRAS status HR 1.20; N2 disease HR1.95; ; having liver metastasis compared to lung HR 1.65 ;. Factors associated with improved survival were CEA less than 30 ng/ml at diagnosis and left sided tumor with HR of 0.64 (0.56-0.72) and 0.75(0.67-0.84) respectively. Conclusions: Metastatic colon cancer with single organ liver or lung lesions benefit from neoadjuvant chemotherapy based on our analysis of the real-world data. The survival advantage in this setting has not been shown before.

Metastasectomy for Stage IVA Colon Cancer: Does the Type of Treating Institution Make a Difference?

2021 ◽  
pp. 000313482110233
Author(s):  
Shinho T. Kang ◽  
Ryan Moran ◽  
Lala Hussain ◽  
Hamza Guend ◽  
Erik M. Dunki-Jacobs ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Liver Metastasis ◽  
Complex Disease ◽  
Academic Research ◽  
Disease Process ◽  
Tumor Location ◽  
Colon Resection ◽  
Academic Community ◽  
Metastatic Colon Cancer ◽  
Isolated Liver

Treatment of metastatic colon cancer has evolved over time. More evidence has been emerging in recent years supporting metastasectomy in selected patients. We sought to elucidate whether the type of institution—community, comprehensive community, academic/research, and integrated cancer network—would have an effect on patient outcome, specifically those colon cancer patients with isolated liver metastasis. This retrospective cohort study queried the National Cancer Database (NCDB) from 2010 to 2014 for patients who were 18 years of age or older with stage IVA colon cancer with isolated liver metastasis. We then performed uni- and multivariate analyses comparing patients based on such factors as age, tumor characteristics, primary tumor location, rate of chemotherapy, and type of treating institution. Patients who came from regions of higher income, receiving chemotherapy, and presenting to an academic/research hospital were more likely to undergo metastasectomy. Median survival was longest at academic/community hospitals at 22.4 months, 6 to 7 months longer than the other three types of institutions. Factors positively affecting survival included receiving chemotherapy, presenting to an academic/research institution, and undergoing metastasectomy, all at P < .05. In our study, the rate of metastasectomy was more than double at academic/research institutions for those with stage IVA colon cancer with isolated liver metastasis. Prior studies have quoted a mere 4.1% synchronous colon resection and metastasectomy. Our findings suggest that we should maintain multidisciplinary approach to this complex disease process and that perhaps it is time for us to consider regionalization of care in treating metastatic colon cancer.

Outcome of colon cancer patients with synchronous metastases

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4029-4029
Author(s):  
I. Sobhani ◽  
F. Roudot-Thoraval ◽  
F. Mesli ◽  
B. Landi ◽  
T. Aparicio ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Cancer Patients ◽  
Cox Model ◽  
Univariate Analysis ◽  
Colon Surgery ◽  
Teaching Hospitals ◽  
Rank Test ◽  
Metastatic Colon Cancer ◽  
Curative Surgery ◽  
Synchronous Metastases

4029 Background: Metastatic colon cancer patients may undergo chemotherapy without colon surgery. However, the outcome of patients has not been evaluated and antiagiogenic agents can not be given. The aim of the present cohort study was to analyse factors influencing patients’ survival. Methods: Consecutive patients [N=228, mean age (sd) 64 (12) yrs, median follow-up 20 mths;84 females] treated in 6 teaching hospitals received chemotherapy for metastatic colonic cancer, either as the first step, or after surgery. Progressive free survival (PFS) was estimated using Kaplan-Meïer method. Factors associated with PFS were tested by means of Log rank test and results are presented in terms of medians of survival (95% CI). Factors independently related to PFS were tested using a Cox model and results are presented as hazard ratio. Results: 105 patients with colon cancer and synchronous metastatsis underwent colon surgery prior to chemotherapy (68 males, mean age 64 yrs) when 123 patients were treated first by chemotherapy ± biotherapy (76 males, mean age 63 yrs). By univariate analysis, following factors were significantly associated with PFS: surgery first 25.5 (18.6 - 32.5) vs chemotherapy first 18.3 (14.7 - 21.9) mths p = 0.006; curative surgery: yes 35.7 (29.6 - 41.8) vs no 18.4 (15.6 - 21.2) mths p < 0.001; tumour histological differentiation : no : 13.4 (6.2 - 20.6) vs well : 24.7 (20.4 - 29.1) mths p<0.001; synchronous metastases: liver only 25.5 (20.5 - 30.6) vs peritonea&nodes : 18.4 (10.6 - 26.1) vs pulmonary & other sites : 16.5 (14.7 - 18.3) mths p < 0.0001; need for colonic stent: yes 16.4 (9.3 - 23.5) vs no 23.9 (21.1 - 26.7) months p < 0.0001; antiangiogenic drug: yes 36.6 (28.7 - 44.5) vs no : 20.7 (18.3 - 23.1) p = 0.033. After Cox multivariate analysis five independent factors were found to be associated with PFS. Conclusions: Colon surgery before chemotherapy plus bevacizumab appears to be the more appropriate choice, and associated with longer PFS, especially for those patients with well differentiated tumours and synchronous liver metastases. [Table: see text] No significant financial relationships to disclose.

Single hepatocellular carcinoma (HCC) ineligible for surgical resection (SR): High tumor control rate with conformal radiotherapy + transarterial chemoembolization (CRT + TACE).

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 433-433
Author(s):  
Philippe Merle ◽  
Agnes Rode ◽  
Anne-Frederique Manichon ◽  
Nadim Fares ◽  
Celia Prevost ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Proportional Hazards ◽  
Univariate Analysis ◽  
Cox Proportional Hazards ◽  
Tumor Control ◽  
Continuous Variables ◽  
Tumor Control Rate ◽  
Curative Therapy ◽  
Poor Outcome ◽  
Small Hcc

433 Background: SR is a curative therapy of single HCC. CRT is efficient for small HCC (≤ 5 cm), whereas its combination to TACE (CRT+TACE) is needed for large ( > 5 cm) HCC. However, SR remains the gold-standard in guidelines for large HCC. This work aims to compare these approaches. Methods: Retrospective analysis of prospectively collected data, on patients (pts) included at Lyon North Hepatobiliary Centre, Child-Pugh-A, single HCC. CRT+TACE was decided at the HCC board by ineligibility for SR, radiofrequency or liver transplantation. Outcome of pts was compared between CRT+TACE and SR. Continuous variables were assessed by the t-Student test, and survival analysis by the Cox proportional-hazards regression. Results: 178 pts (68 CRT+TACE, 110 SR), males 78%, cirrhosis 52%, etiology (alcohol 46%, HCV 17%, HBV 13%, NASH 30%), 103 small, 75 large HCC, median age 66 ys, tumor size 50 mm, AFP 8 ng/mL, albuminemia (ALB) 39 g/L, platelets (PLAT) 166 Giga/L, follow-up 33 months. CRT+TACE complete response rate: 92% small / 80% large HCC. Small HCC comparison: CRT+TACE vs SR: age (67 vs 64, P= NS), cirrhosis (94% vs 47%, P< 0.0001), ALB (36 vs 40, P= 0.0001), PLAT (150 vs 201, P= 0.02), AFP (381 vs 300, P= NS). CRT-TACE was a poor outcome factor in univariate analysis for overall survival (OS) (HR 2.32; P= 0.01), progression-free survival (PFS) (HR 1.90; P= 0.007), but did not remain independent in multivariate analysis due to combined factors: age > 70, cirrhosis, ALB < 35, PLAT < 100. Large HCC comparison: CRT+TACE vs SR: age (73 vs 62, P= 0.0008), cirrhosis (70% vs 25%, P= 0.0004), ALB (38 vs 39, P= NS), PLAT (173 vs 240, P= 0.01), AFP (5616 vs 3456, P= NS). CRT-TACE was a poor outcome factor only for OS (HR 3.01; P= 0.0007) in univariate analysis. After adjustment to other factors (age > 70, cirrhosis, PLAT < 100), CRT-TACE was not independent in multivariate analysis for OS ( P= 0.19). Conclusions: CRT+TACE induced an encouraging tumor control rate in a population of older pts, more deteriorated chronic hepatopathy than pts treated by SR. Especially for large HCC, SR was not better than CRT+TACE on the outcome. Prospective randomized trials are warranted to confirm these data.

Can sidedness predict for survival in primary locoregional colon cancers?

2018 ◽  
Vol 36 (4_suppl) ◽  
pp. 584-584
Author(s):  
Weining Wang ◽  
Chin Jin Seo ◽  
Grace Hwei Ching Tan ◽  
Claramae Shulyn Chia ◽  
Khee Chee Soo ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Multivariate Analysis ◽  
Proportional Hazards ◽  
Cox Regression ◽  
Rank Test ◽  
Rectosigmoid Junction ◽  
Colon Cancers ◽  
Kaplan Meier ◽  
Significant Difference ◽  
The Impact

584 Background: Right and left-sided colon cancers are embryonically distinct and present differently. Recently, there has been growing belief that sidedness could be independently associated with survival outcomes. This has important clinical implications regarding the prognostication, management and surveillance of colon cancer patients. Hence, we aim to investigate the impact of sidedness on survival in our patient population in this study. Methods: Patients who had primary treatment naïve colon cancer who underwent curative surgical resection in our institution from September 2002 to December 2010 were included in this study. Demographic and clinicopathological data was collected from electronic records and clinical charts. Tumours arising from the cecum, ascending colon, hepatic flexure and transverse colon were considered right-sided, while those arising from splenic flexure and descending colon were considered left-sided. Cancers of the rectosigmoid junction and rectum were excluded. Kaplan-Meier curves and log-rank test were used to compare overall, locoregional recurrence-free and distant recurrence-free survivals (OS, LRFS, DRFS respectively) between both groups. Multivariate analysis was performed using Cox regression proportional hazards. Results: 389 patients were included in this study. 238 had left-sided tumours while the remaining 151 had right-sided tumours. In our cohort, right-sided tumours were associated with older age and mucinous histology. Kaplan-Meier curves plotted showed improved LRFS in left-sided tumours (p = 0.04, median survival not reached) but no significant difference in OS and DRFS. On multivariate analysis, sidedness was also found to be an independent prognostic factor for LRFS but not OS and DRFS despite factoring in age, size of tumour, pT, pN and histology. Conclusions: Our study suggests that left-sided tumours in primary colon cancer are independently prognostic for improved locoregional survival as compared to the right-sided tumours, even after taking into account other known factors such as age, staging and histology.

Mutation profile of colon cancer in hispanic population of central California.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16067-e16067
Author(s):  
Sanjay Hinduja ◽  
Mir Ali ◽  
Mohammed SANI Bukari ◽  
Uzair Bashir Chaudhary ◽  
Tanner Mortenson ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Microsatellite Instability ◽  
Metastatic Disease ◽  
Pik3ca Mutation ◽  
Population Based ◽  
Metastatic Colon Cancer ◽  
Hispanic Population ◽  
Central California ◽  
Mutation Profile ◽  
Hispanic Patients

e16067 Background: The clinical and mutational profile of Hispanic patients with metastatic colon cancer is not well documented. In this retrospective study, we aim to describe the clinical and mutational profile of Hispanic patients with metastatic colon cancer in central California. Methods: We retrospectively evaluated the clinical and mutational profile of colon cancer at a single institution in Fresno, California from 2010-2019. We selected 136 patients out of which 70 patients self-identified as Hispanic and 66 self-identified as non-Hispanic. We studied clinical parameters and next-generation sequencing via Foundation one testing for these patients. Results: Among Hispanics, there were 43(61%) males and 27(38%) females. The median age at diagnosis was similar in both groups at 57. Right sided colon cancer accounted for 52% of Hispanic patients versus 40% in non-Hispanics. Fifty two percent of Hispanic patients presented with metastatic disease versus 45% in non-Hispanics. The frequency of commonly mutated genes in colon cancer in Hispanics versus non-Hispanics are as follows. KRAS (35.7% vs 37%), NRAS (11% vs 4%) BRAF (8% vs 7%), Her2/neu 0% in both groups. The frequency of other mutations such as TP53, APC, ATM, PTEN, CDKN2A, Myc amplification were also noted to be similar in both groups. PIK3CA mutation was seen in 18.6% of Hispanic patients versus 34% in non-Hispanic population which was statistically significant with a p value = 0.032. Microsatellite instability (MSI) was seen at 3.3% in Hispanics versus 10.6% in non-Hispanics. Tumor mutational burden was similar in both groups. Conclusions: The frequency of actionable mutations was similar in both Hispanic and non-Hispanic patients. Hispanics were noted to have lower PIK3CA and microsatellite instability. Metastatic disease and right sided colon cancer were seen at higher frequency in Hispanic population. Our results were similar to another population-based study which analyzed KRAS mutation with colon cancer patients in Puerto Rico[1]. Larger population based studies would be needed to further assess the differences in this patient population. Ruiz-Candelaria, Y., C. Miranda-Diaz, and R.F. Hunter-Mellado, K-RAS mutation profile in Puerto Rican patients with colorectal cancer: trends from April 2009 to January 2011. Int J Biol Markers, 2013. 28(4): p. e393-7.

Development of a clinically feasible molecular assay to predict recurrence of Dukes’ B colon cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 20110-20110
Author(s):  
Y. Jiang ◽  
Y. Zhang ◽  
T. Briggs ◽  
D. Talantov ◽  
A. Mazumder ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Multivariate Analysis ◽  
Cancer Patients ◽  
Therapeutic Option ◽  
Univariate Analysis ◽  
Clinical Importance ◽  
Gene Signature ◽  
Rt Pcr ◽  
Pcr Assay ◽  
Tissue Samples

20110 Background: The 5-year survival rate of Dukes’ B colon cancer patients is approximately 75%. In our earlier genome-wide measurements of gene expression we have identified a 23-gene signature that sub-classifies Dukes’ B tumors and may provide better means of risk assessment on an individual basis for these colon cancer patients. The aim of this study is to validate this gene signature in an independent and more diverse group of patients, and further develop this prognostic signature into a clinical feasible test using formalin-fixed paraffin-embedded (FFPE) tissue samples. Methods: Using Affymetrix U133a GeneChip we analyzed the expression of the 23 genes in total RNA of frozen tumor samples from 123 Dukes’ B patients who did not receive adjuvant systemic treatment. Furthermore, we developed a quantitative RT-PCR assay for this gene signature in order to perform the test with standard clinical FFPE samples. Results: In the independent validation set of 123 patients, the gene signature proved to be informative in identifying patients who would develop distant metastasis (hazard ratio, HR 2.56; 95% confidence interval CI, 1.01–6.48), even when corrected for the traditional prognostic factors in multivariate analysis (HR, 2.73; 95% CI, 0.97–7.73). The RT-PCR assay developed for this gene signature was also validated in an independent set of 114 patients as a strong prognostic factor for the development of distant recurrence (HR, 6.38; 95% CI, 2.88–14.2) in univariate analysis and in multivariate analysis (HR, 13.3; 95% CI, 5.13–34.4). Conclusions: Our data provide not only a validation of the pre-defined prognostic gene signature for Dukes’ B colon cancer patients but also a clear feasibility of testing the gene signature using RT-PCR with standard FFPE specimens. The ability of such a test to identify patients that have an unfavorable outcome demonstrates potential clinical importance that could lead clinicians to choose a more aggressive therapeutic option for the high-risk patients. [Table: see text]

Serum insulin to predict time to castration-resistant progression and overall survival in metastatic androgen-dependent prostate cancer (mADPCa).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e16038-e16038
Author(s):  
Farshid Dayyani ◽  
Graciela M. Nogueras-Gonzalez ◽  
Rebecca Slack ◽  
Randall E. Millikan ◽  
Amado J. Zurita ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Cancer Progression ◽  
Proportional Hazards ◽  
Serum Insulin ◽  
Univariate Analysis ◽  
Cox Proportional Hazards ◽  
Insulin Levels ◽  
Castration Resistant

e16038 Background: Duration of response to androgen-deprivation therapy (ADT) is highly variable in patients with mADPC and prognostic markers are needed. Insulin resistance and hyperinsulinemia may contribute to prostate cancer progression. We hypothesized that pretreatment serum insulin levels would predict time to castration-resistant progression (PFS) and overall survival (OS). Methods: Sera from men treated on a randomized phase 3 trial of first line ADT vs. ADT plus chemotherapy were retrospectively analyzed using a multiplex ELISA for cytokines and angiogenic factors (CAFs). Univariate and multivariate Cox proportional hazards regression models were used to identify associations between CAFs and PFS/OS. Results: 66 pts were evaluable, 86% Caucasian, median age 72 yrs, median PSA 31.5ng/mL, 77% Gleason score of ≥8, and 53% high volume metastatic disease (HVM). Thirty-five pts received ADT; 31 pts received ADT+chemo. In univariate analysis, higher pretreatment insulin and C-peptide were positively correlated with PFS, whereas higher hepatocyte-growth factor (HGF), osteopontin (OPN) and HVM were negatively correlated with PFS. In multivariate analysis, only higher insulin was associated with longer PFS (HR=0.72, 95%CI 1.32 -0.87; p<0.001), whereas higher HGF and OPN were associated with reduced PFS (HR=1.82, 95%CI 0.59-2.83, p<0.01 and HR=1.81, 95%CI 1.18-2.47, p<0.001, respectively). Higher Insulin and Program Death 1 (PD1) were associated with longer OS on multivariate analysis (HR=0.78 p<0.02 and HR=0.55 p<0.02, respectively), whereas HVM and higher OPN were associated with reduced OS (HR=2.28 p<0.01 and HR=1.60 p<0.02). Using low insulin, high HGF and high OPN as 3 independent risk factors (RF), 3 distinct risk groups could predict PFS: good (zero RF), intermediate (1 or 2 RF) and poor risk (3 RF), with median PFS of 6.90, 1.97, and 0.86 years, respectively (p<0.001). Conclusions: Higher pretreatment insulin was associated with prolonged PFS and OS in men with mADPC treated with ADT. Our data suggest that insulin levels are a biomarker for sensitivity to ADT and highlight the complex interactions between metabolism and PCa progression.

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.

Clusterin expression (CLU) as a prognostic marker in colorectal carcinoma (CCR).

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 563-563
Author(s):  
Julia Alcaide ◽  
Antonio Rueda ◽  
Isabel Rodrigo ◽  
Teresa Tellez ◽  
Rafael Funez ◽  
...  
Keyword(s):  
Multivariate Analysis ◽  
Proportional Hazards ◽  
Proportional Hazards Model ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Normal Mucosa ◽  
Cox Proportional Hazards ◽  
Cox Proportional Hazards Model ◽  
Staining Procedure ◽  
Positive Staining

563 Background: Increased CLU is involved in malignant progression and anticlusterin treatment with antisense oligonucleotides enhances apoptosis induced by several citotoxics. However, clinical significance of CLU expression in human CRCs has been scarcely studied. We investigated whether changes in CLU could be related to carcinogenesis and survival (sv) of CRC patients (pts). Methods: Formalin-fixed and paraffin-embedded specimens were examined from 31 adenomas and 103 CRCs resected at Costa del Sol Hospital. The study was approved by Research Ethics Committee. Immunohistochemistry using monoclonal anti-α chain clusterin antibody (Upstate-Millipore, Watford, England) was performed, following standard staining procedure. CLU was scored as negative (CLU–) (no staining) or positive (CLU +) (>10% of tumor cells with strong staining). Cytoplasmic CLU in tumors was evaluated for cancer cells only, and in normal mucosa for epithelial cells only. Sv curves were calculated and plotted according to Kaplan-Meier method. Predictors that were significant at p<0.10 in univariate analysis, were entered into a Cox proportional hazards model for multivariate analysis, remaining significant at p<0.05. Results: Median follow-up was 54 months. Median age was 70 years (45-91). TNM stage distribution was: I (13%), II (48%), III (25%) and IV (14%). Epithelial normal cells were always CLU-, but 16% (5/31) of adenomas was CLU+ and this percentage increased in CRCs (30%, 31/103). Positive staining always presented an apical cytoplasmic pattern. Recurrence was more frequent in CLU+ (61%,19/ 31) than in CLU- tumors (37%, 27/72) and CLU was significantly associated with lower disease-free survival (DFS) (p<0.05). In multivariate analysis, CLU and stage remained significant independent prognostic factors for DFS (Table). Conclusions: CLU has a role in colon carcinogenesis and prognostic value. CLU is associated with decreased DFS among pts with CRCs. These findings have important implications for identifying CRC pts with more aggressive tumors who may benefit from targeted therapy against clusterin. [Table: see text]

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