Survival In Rectal Cancer Patients Research Articles

Postoperative carcinoembryonic antigen level has a prognostic value for distant metastasis and survival in rectal cancer patients who receive preoperative chemoradiotherapy and curative surgery: a retrospective multi-institutional analysis.

The cut-off value and prognostic significance of postoperative carcinoembryonic antigen (CEA) level in rectal cancer after preoperative chemoradiotherapy (CRT) and curative surgery are still unclear. 1559 rectal cancer patients staged with cT3-4N0-2M0 received preoperative CRT and total mesorectal excision (TME). CEA levels were measured before CRT and 3-4weeks after surgery. Clinicopathologic factors that could be associated with tumor recurrence and patient survival were analyzed. The cumulative probability of tumor recurrence showed a steep increase with a cutoff value of 2.5ng/mL for postoperative CEA level, and the gradient decreased as the CEA levels increased above 2.5ng/mL. After a median follow-up time of 46.7months, patients with postoperative CEA level>2.5ng/mL had significantly lower relapse-free survival (RFS) (65.2 vs. 75.6%, P<0.001) and overall survival (OS) (78.1 vs. 88.3%, P<0.001) at 5years than patients with postoperative CEA level≤2.5ng/mL. On the multivariate analysis, postoperative CEA level was a significant prognostic factor for RFS (HR 1.561; 95% CI 1.221-1.996; P<0.001) and OS (HR 2.073; 95% CI 1.498-2.869; P<0.001). Postoperative CEA level independently affected RFS irrespective of pre-CRT CEA level. Postoperative CEA level was a significant predictor for distant recurrence (P=0.004), but not for locoregional recurrence (P=0.472). Postoperative CEA level>2.5ng/ml is a predictor of distant metastasis and a negative prognostic factor for survival in rectal cancer patients who receive preoperative CRT and curative surgery.

Impact of anastomotic leak on recurrence and survival after colorectal cancer surgery: a BioGrid Australia analysis.

There is conflicting evidence regarding the oncological impact of anastomotic leak following colorectal cancer surgery. This study aims to test the hypothesis that anastomotic leak is independently associated with local recurrence and overall and cancer-specific survival. Analysis of prospectively collected data from multiple centres in Victoria between 1988 and 2015 including all patients who underwent colon or rectal resection for cancer with anastomosis was presented. Overall and cancer-specific survival rates and rates of local recurrence were compared using Cox regression analysis. A total of 4892 patients were included, of which 2856 had completed 5-year follow-up. The overall anastomotic leak rate was 4.0%. Cox regression analysis accounting for differences in age, sex, body mass index, American Society of Anesthesiologists score and tumour stage demonstrated that anastomotic leak was associated with significantly worse 5-year overall survival (χ 2 = 6.459, P = 0.011) for colon cancer, but only if early deaths were included. There was no difference in 5-year colon cancer-specific survival (χ 2 = 0.582, P = 0.446) or local recurrence (χ 2 = 0.735, P = 0.391). For rectal cancer, there was no difference in 5-year overall survival (χ 2 = 0.266, P = 0.606), cancer-specific survival (χ 2 = 0.008, P = 0.928) or local recurrence (χ 2 = 2.192, P = 0.139). Anastomotic leak may reduce 5-year overall survival in colon cancer patients but does not appear to influence the 5-year overall survival in rectal cancer patients. There was no effect on local recurrence or cancer-specific survival.

Association of perioperative blood pressure with long-term survival in rectal cancer patients.

BackgroundSeveral studies suggested that hypertension is positively related to cancer incidence and mortality. In this study, we investigated the association between perioperative blood pressure (BP) and long-term survival outcomes in patients with rectal cancer.MethodsThis study included a cohort of 358 patients with stages I–III rectal cancer who underwent a curative resection between June 2007 and June 2011. Both pre- and postoperative BPs were measured, by which patients were grouped (low BP: <120/80 mmHg; high BP: ≥120/80 mmHg). The survival outcomes were compared between these two groups. The primary endpoints were disease-free survival (DFS) and cancer-specific survival (CSS).ResultsUnivariate analysis showed that patients with high preoperative systolic BP had lower 3-year DFS (67.2% vs. 82.1%, P = 0.041) and CSS rates (81.9% vs. 94.8%, P = 0.003) than patients with low preoperative systolic BP, and the associations remained significant in the Cox multivariate analysis, with the adjusted hazard ratios equal to 1.97 [95% confidence interval (CI) = 1.08–3.60, P = 0.028] and 2.85 (95% CI = 1.00–8.25, P = 0.050), respectively. Similarly, in postoperative evaluation, patients with high systolic BP had significantly lower 3-year CSS rates than those with low systolic BP (78.3% vs. 88.9%, P = 0.032) in univariate analysis. Moreover, high pre- and/or postoperative systolic BP presented as risk factors for CSS in the subgroups of patients who did not have a history of hypertension, with and/or without perioperative administration of antihypertensive drugs.ConclusionsHigh preoperative systolic BP was an independent risk factor for both CSS and DFS rates, and high postoperative systolic BP was significantly associated with a low CSS rate in rectal cancer patients. Additionally, our results suggest that rectal cancer patients may get survival benefit from BP control in perioperative care. However, further studies should be conducted to determine the association between BP and CSS and targets of BP control.

Differential effects of patient-related factors on the outcome of radiation therapy for rectal cancer.

The objective of this study was to investigate whether cancer specific survival in rectal cancer patients is affected by patient-related factors, conditional on radiation treatment. 359 invasive rectal cancer patients who consented and provided questionnaire data for a population-based case-control study of colorectal cancer in Metropolitan Detroit were included in this study. Their vital status was ascertained through to the population-based cancer registry. Hazard ratios (HR) for cancer specific and other deaths and 95% confidence intervals (CIs) were calculated according to selected patients' characteristics, stratified by radiation status, using joint Cox proportional hazards models. A total of 159 patients were found to be deceased after the median follow-up of 9.2 years, and 70% of them were considered to be cancer specific. Smoking and a history of diabetes were associated with an increased probability of deaths from other causes (HR 3.20, 95% CI 1.72-5.97 and HR 2.02, 95% CI 0.98-4.16, respectively), while regular use of non-steroidal anti-inflammatory drugs (NSAIDs) was inversely correlated with cancer-specific mortality (HR 0.50, 95% CI 0.30-0.81). Furthermore, the associations of smoking and NSAIDs with the two different types of deaths (cancer vs others) significantly varied with radiation status (P-values for the interactions= 0.014 for both). In addition, we observed a marginally significantly reduced risk of cancer specific deaths in the patients who had the relative ketogenic diet overall (HR=0.49, 95% 0.23-1.02). Further research is warranted to confirm these results in order to develop new interventions to improve outcome from radiation treatment.

Significance of histologic tumor grade in rectal cancer treated with preoperative chemoradiotherapy followed by curative surgery: A multi-institutional retrospective study

Background and purposeTo evaluate the pre-treatment clinical factors affecting recurrence and survival in rectal cancer patients who receive preoperative chemoradiotherapy (CRT) and curative surgery. Methods and materialsThe clinical data of 1782 patients from 8 institutions in Korea were analyzed. The potential prognostic factors that could be acquired before radical surgery were patient age, gender, clinical T and N stages, tumor size and location, tumor grade, carcinoembryonic antigen (CEA) level, and the concurrent chemotherapy regimen. The relapse-free survival (RFS), overall survival (OS), and cumulative incidence of locoregional and distant recurrence were analyzed according to the clinical factors. ResultsAmong the pre-treatment clinical factors, tumor grade, pre-CRT CEA level, tumor location, and clinical N stage were significant prognostic factors affecting the RFS. The high-grade tumor was the hazardous factor for RFS on the multivariate analysis [Hazard ratio (HR), 1.83; 95% confidence interval (CI), 1.29–2.58; p=0.001]. The 5-year RFS rate for high-grade tumors was significantly lower than that for low-grade tumors (63.8% vs. 78.8%, p<0.001). The tumor grade was a significant prognostic factor for distant recurrence (HR, 1.83, 95% CI, 1.29–2.58; p<0.001), but not for locoregional recurrence (HR, 1.49, 95% CI, 0.68–3.26; p=0.320) on the multivariate analysis. The 5-year OS rate for high-grade tumors was significantly lower than that for low-grade tumors (70.6% vs. 85.5%, p<0.001). ConclusionThe tumor grade is the significant pre-treatment clinical factor for recurrence and survival in rectal cancer patients who receive preoperative CRT and curative surgery.

Prognostic Relevance of Mucinous Subtype in a Population-based Propensity Score Analysis of 40,083 Rectal Cancer Patients.

The prognostic relevance of mucinous histology in colorectal cancer remains unclear, especially for rectal neoplasms. The objective of this study was to evaluate if mucinous subtype has a relevant impact on overall survival (OS) and cancer-specific survival (CSS) of patients with adenocarcinomas of the rectum. On the basis of the data set of the Surveillance, Epidemiology, and End Results Program of the National Cancer Institute of the United States, patients with rectal cancer between 2004 and 2011 were identified. Risk-adjusted Cox regression analysis and propensity score methods were used to assess OS and CSS. In total, 40,083 patients with stage I-IV rectal cancer, of whom 2483 (6.2%) had mucinous histology, were included in this study. In unadjusted analysis, the 5-year OS and CSS for patients with a mucinous adenocarcinoma was 54.3% [95% confidence interval (CI) 52.0-56.7] and 61.4% (95% CI 59.1-63.9) compared to 66.4% (95% CI 65.8-67.0) and 74.5% (95% CI 73.9-75.1) for patients with nonmucinous adenocarcinoma (P<0.001). The survival disadvantage persisting in risk-adjusted Cox proportional hazard regression analysis [hazard ratio (HR) 1.23, 95% CI 1.15-1.31, P<0.001 and 1.25, 95% CI 1.16-1.35, P<0.001) disappeared after propensity score matching (OS: HR=0.96, 95% CI 0.76-1.21, P=0.722; CSS: HR 1.06, 95% CI 0.80-1.40, P=0.693). This population-based, propensity score matched analysis shows that mucinous histology itself does not constrain survival in rectal cancer patients. Therefore, treatment decisions should not be different according to mucinous histology.

Prognostic Significance and Molecular Features of Colorectal Mucinous Adenocarcinomas

Mucinous adenocarcinoma (MC) is a special histology subtype of colorectal adenocarcinoma. The survival of MC is controversial and the prognostic biomarkers of MC remain unclear. To analyze prognostic significance and molecular features of colorectal MC. This study included 755,682 and 1001 colorectal cancer (CRC) patients from Surveillance, Epidemiology, and End Results program (SEER, 1973-2011), and Linköping Cancer (LC, 1972-2009) databases. We investigated independently the clinicopathological characteristics, survival, and variety of molecular features from these 2 databases. MC was found in 9.3% and 9.8% patients in SEER and LC, respectively. MC was more frequently localized in the right colon compared with nonmucinous adenocarcinoma (NMC) in both SEER (57.7% vs 37.2%, P < 0.001) and LC (46.9% vs 27.7%, P < 0.001). Colorectal MC patients had significantly worse cancer-specific survival (CSS) than NMC patients (SEER, P < 0.001; LC, P = 0.026), prominently in stage III (SEER, P < 0.001; LC, P = 0.023). The multivariate survival analysis showed that MC was independently related to poor prognosis in rectal cancer patients (SEER, hazard ratios [HR], 1.076; 95% confidence intervals [CI], 1.057-1.096; P < 0.001). In LC, the integrated analysis of genetic and epigenetic features showed that that strong expression of PINCH (HR, 3.954; 95% CI, 1.493-10.47; P = 0.013) and weak expression of RAD50 (HR 0.348, 95% CI, 0.106-1.192; P = 0.026) were significantly associated with poor CSS of colorectal MC patients. In conclusion, the colorectal MC patients had significantly worse CSS than NMC patients, prominently in stage III. MC was an independent prognostic factor associated with worse survival in rectal cancer patients. The PINCH and RAD50 were prognostic biomarkers for colorectal MC patients.

KRAS Mutation Status Is Not a Predictor for Tumor Response and Survival in Rectal Cancer Patients Who Received Preoperative Radiotherapy With 5-Fluoropyrimidine Followed by Curative Surgery

We evaluated the tumor response and survival according to the KRAS oncogene status in locally advanced rectal cancer. One hundred patients with locally advanced rectal cancer (cT3-4N0-2M0) received preoperative radiation of 50.4 Gy in 28 fractions with 5-fluorouracil and total mesorectal excision. Tumor DNA from each patient was obtained from pretreatment biopsy tissues. A Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation was found in 26 (26%) of the 100 patients. Downstaging (ypT0-2N0M0) rates after preoperative chemoradiotheray were not statistically different between the wild-type and mutant-type KRAS groups (30.8% vs 27.0%, P = 0.715, respectively). After a median follow-up time of 34 months, there was no statistically significant difference in the 3-year relapse-free survival (82.2% vs 82.6%, P = 0.512) and overall survival (94.7% vs 92.3%, P = 0.249) rates between wild-type and mutant-type KRAS groups, respectively. The KRAS mutation status does not influence the tumor response to the radiotherapy and survival in locally advanced rectal cancer patients who received preoperative chemoradiotherapy and curative surgery.

A population-based study elicits a reverse correlation between age and overall survival in elderly patients with rectal carcinoma receiving adjuvant chemotherapy.

Colorectal cancer is the third most common cancer and the fourth most common cause of cancer-related death globally. This population-based study aimed to explore the predictive factors that affected the overall survival of rectal cancer patients receiving adjuvant chemotherapy plus radical surgery using a Cox proportional hazards modeling approach. A total of 619 patients with rectal cancer who underwent surgery were enrolled between October 2006 and May 2013. Clinical characteristics of the patients were compared among the groups and potential prognostic factors were analyzed using the spss program, version 19.0. Patients aged ≥ 70 years have distinctive characteristics such as lager tumour size (≥ 5 cm), damaged micturition and higher incidence of diabetes compared to younger and middle-aged patients. Male gender, tumour size (≥ 5 cm), poor differentiation, later stage, adjuvant chemotherapy, damaged micturition, hypertension or diabetes are associated with a worse prognosis for rectal cancer patients (P < 0.05). However, smoking is a favourable factor to the patients (P = 0.018). Age of ≥ 70 years is an independent prognostic factor for patients with rectal cancer after surgery (P = 0.000) and elderly patients with Stage II and III disease receiving adjuvant chemotherapy show a favourable prognosis. The elderly patients who suffered from diabetes receiving adjuvant chemotherapy have a poor prognosis. Further prospective and large population studies are warranted to confirm the findings of this study.

Retrospective analysis of 856 cases with stage 0 to III rectal cancer underwent curative surgery combined modality therapy

To investigate the survival and prognostic factors of stage 0 to III rectal cancer in 10 years. Clinical data and follow-up of 856 rectal cancer patients with stage 0-III underwent curative surgery from January 2000 to December 2010 were retrospective analyzed. There were 470 male and 386 female patients, with a mean age of (58 ± 12) years. Kaplan-Meier method was used to analyze the overall survival and disease free survival. Log-rank test was used to compare the survival between groups. Cox regression was used to analyze the independent prognostic factors of rectal cancer. The patients in each stage were stage 0 with 18 cases, stage I with 209 cases, stage II with 235 cases, and stage III with 394 cases. All patients received curative surgery. There were 296 patients evaluated as cT3, cT4 and any T with N+ received preoperative radiotherapy. 5.4% patients got pathological complete response (16/296), and the recurrence rate was 4.7% (14/296). After a median time of 41.7 months (range 4.1 to 144.0 months) follow-up, the 5-year overall survival rate in stage 0 to I of was 91.0%, stage II 86.2%, and stage III 60.0%, with a significant difference (P=0.000). The cumulative local recurrence rate was 4.8% (41/856), of which 70.7% (29/41) occurred within 3 years postoperatively, 97.6% (40/41) in 5 years. The cumulative distant metastasis rate was 16.4% (140/856), of which 82.9% (129/140) occurred within 3 years postoperatively, 96.4% (135/140) in 5 years. The incidence of abnormal imaging findings was significantly higher in pulmonary than liver and other sites metastases (75.0% vs. 21.7%, χ² =25.691, P=0.000). The incidence of CEA elevation was significantly higher in liver than lung and other sites metastases (56.8% vs. 37.8%, χ² =25.691, P=0.000). Multivariable analysis showed that age (P=0.015, HR=1.385, 95% CI: 1.066 to 1.801), surgical approach (P=0.029, HR=1.337, 95% CI: 1.030 to 1.733), differentiation (P=0.000, HR=1.535, 95% CI: 1.222 to 1.928), TNM stage (P=0.000, HR=1.349, 95% CI: 1.260 to 1.444) and lymphovascular invasion (P=0.001, HR=1.715, 95% CI: 1.258 to 2.342) are the independent prognostic factors for rectal cancer. Age, surgical approach, differentiation, TNM stage and lymphovascular invasion are independent prognostic factors for rectal cancer. Preoperative evaluation and combined modality therapy can significant reduce the local recurrence and improve overall survival for rectal cancer patients.

SU‐E‐T‐739: The Logistic Regression and Cox Regression Model for Predicting Local Recurrence, Distant Metastases, and Overall Survival of Rectal Cancer Patients

Purpose:The purpose was to develop predicting models for the local recurrence, distant metastases, and overall survival for rectal cancer patients treated with chemoradiotherapy. These models were based on different statistical methods for indicating various relationships between clinical features and follow‐up results, which may provide support on decision‐making in treatment.Methods:Models were developed based on logistic regression and cox proportional hazards model using patient data (N=277) from Fudan University Shanghai Cancer Center. The patient data set was randomly split into two proportions as the training and validation datasets. The clinical features used as variables include sex, age, tumor location, RT dose, adjuvant chemotherapy, surgery procedure, clinical tumor stage, and pTNM stage. The Bootstrapping was used for constructing confidence intervals; and the model performance was evaluated by the concordance index (c‐index).Results:The logistic regression model is easy to use because the conditional independence assumption is unnecessary. The Cox regression model can dispose data with time factors so follow‐up over a certain time period can be predicted. For the logistic regression model, the c‐index for validation are 0.73 (LR), 0.77 (DM), and 0.76(OS), while numerical values for the cox regression model are 0.72 (LR), 0.77 (DM), and 0.70(OS). Both models show the probability to predict follow‐up events based on c‐index. Clinical tumor stage and pathologic stage are crucial features for both models (p&lt;0.05).Conclusion:The Logistic Regression and Cox Regression Model can be used for Predicting Local Recurrence, Distant Metastases, and Overall Survival of Rectal Cancer Patients. The performance of models can be further improved with additional parameters provided from different facilities.

SU‐E‐J‐256: Predicting Metastasis‐Free Survival of Rectal Cancer Patients Treated with Neoadjuvant Chemo‐Radiotherapy by Data‐Mining of CT Texture Features of Primary Lesions

Purpose:The purpose of this study is to investigate the relationship between computed tomographic (CT) texture features of primary lesions and metastasis‐free survival for rectal cancer patients; and to develop a datamining prediction model using texture features.Methods:A total of 220 rectal cancer patients treated with neoadjuvant chemo‐radiotherapy (CRT) were enrolled in this study. All patients underwent CT scans before CRT. The primary lesions on the CT images were delineated by two experienced oncologists. The CT images were filtered by Laplacian of Gaussian (LoG) filters with different filter values (1.0–2.5: from fine to coarse). Both filtered and unfiltered images were analyzed using Gray‐level Co‐occurrence Matrix (GLCM) texture analysis with different directions (transversal, sagittal, and coronal). Totally, 270 texture features with different species, directions and filter values were extracted. Texture features were examined with Student's t‐test for selecting predictive features. Principal Component Analysis (PCA) was performed upon the selected features to reduce the feature collinearity. Artificial neural network (ANN) and logistic regression were applied to establish metastasis prediction models.Results:Forty‐six of 220 patients developed metastasis with a follow‐up time of more than 2 years. Sixtyseven texture features were significantly different in t‐test (p&lt;0.05) between patients with and without metastasis, and 12 of them were extremely significant (p&lt;0.001). The Area‐under‐the‐curve (AUC) of ANN was 0.72, and the concordance index (CI) of logistic regression was 0.71. The predictability of ANN was slightly better than logistic regression.Conclusion:CT texture features of primary lesions are related to metastasisfree survival of rectal cancer patients. Both ANN and logistic regression based models can be developed for prediction.

The chemokines CXCL9 and CXCL13 as prognostic markers for metastasis and survival in rectal cancer patients after neoadjuvant chemoradiation.

627 Background: Distant metastasis is a challenging problem in multimodal treatment of rectal cancer. Valid prognostic markers for the occurrence of metachronous metastasis could help to stratify patients who qualify for adjuvant chemotherapy and intensified follow-up procedures after preoperative chemoradiotherapy (CRT). Methods: We analysed 9 different genes known to prominently figure in crucial pathways of the tumor cell metabolism. mRNA was isolated and quantified from surgical specimens of 77 rectal cancer patients undergoing neoadjuvant CRT. The panel contains genes with relevant function in apoptosis (Birc5, XIAP, SMAC) and epithelial-mesenchymal transitions (SNAI2) as well as the cancer stem-cell marker CD133, the transcription factor ESR1 and the lymphocyte-chemokines CXCL9 and 13. The expression levels in post-CRT rectal cancers were correlated with the development of distant metastasis and with disease-free (DFS) and cancer-specific overall survival (CSS). Results: Intratumoral mRNA expression of the T-cell chemokine CXCL9 (p&lt;0.001) and the B-cell chemokine CXCL13 (p&lt;0.01) was inversely correlated with the occurrence of distant metastasis. Patients with isolated high CXCL9 (p&lt;0.0001) and CXCL13 levels (p&lt;0.01) had a significantly prolonged DFS. Patients with simultaneous expression of CXCL9 and 13 had an excellent DFS compared to patients without expression of any of the chemokines (p&lt;0.0001). Additionally, CXCL9 expression was correlated with an improved CSS (p&lt;0.05). There was no significant correlation between expression levels of the other genes tested and metastasis or survival. Conclusions: The post-CRT expression of the lymphocyte-chemokines CXCL9 and 13 is associated with reduced rates of distant metastases and improved survival in rectal cancers after CRT. Further investigations are needed to prospectively validate these results and characterize the underlying cellular and molecular mechanisms.

Prognostic Value of Negative Lymph Nodes (NLN) in Rectal Adenocarcinoma

We studied the impact on prognosis by negative LN (NLN) harvest count on rectal cancer patients, using immunohistochemistry to exclude micrometastasis in nodes negative by hematoxylin and eosin (H & E) stain. A prospective study including 114 patients in Mansoura university hospitals between 2005-2008 aged 18 years or older who were diagnosed as having localized invasive adenocarcinoma rectum with stage I, II & III was conducted. Close follow up done in both surgery department and department of clinical oncology and nuclear medicine for 5 years. We examined patient survival in relation to the negative lymph node count. Our results revealed that the number of negative lymph nodes could affect significantly survival curves where the disease free survival and overall survival were significantly better among the group of patients with more than ten negative LNs (P=0.021 & 0.012 respectively). In conclusion, the negative lymph node count is associated with improved survival of rectal cancer patients.

Circulating APRIL levels are correlated with advanced disease and prognosis in rectal cancer patients.

We have previously shown that the tumor necrosis factor family member a proliferation-inducing ligand (APRIL) enhances intestinal tumor growth in various preclinical tumor models. Here, we have investigated whether APRIL serum levels at time of surgery predict survival in a large cohort of colorectal cancer (CRC) patients. We measured circulating APRIL levels in a cohort of CRC patients (n=432) using a novel validated monoclonal APRIL antibody (hAPRIL.133) in an enzyme-linked immunosorbent assay (ELISA) setup. APRIL levels were correlated with clinicopathological features and outcome. Overall survival was examined with Kaplan–Meier survival analysis, and Cox proportional hazards ratios were calculated. We observed that circulating APRIL levels were normally distributed among CRC patients. High APRIL expression correlated significantly with poor outcome measures, such as higher stage at presentation and development of lymphatic and distant metastases. Within the group of rectal cancer patients, higher circulating APRIL levels at time of surgery were correlated with poor survival (log-rank analysis P-value 0.008). Univariate Cox regression analysis for overall survival in rectal cancer patients showed that patients with elevated circulating APRIL levels had an increased risk of poor outcome (hazard ratio (HR) 1.79; 95% confidence interval (CI) 1.16–2.76; P-value 0.009). Multivariate analysis in rectal cancer patients showed that APRIL as a prognostic factor was dependent on stage of disease (HR 1.25; 95% CI 0.79–1.99; P-value 0.340), which was related to the fact that stage IV rectal cancer patients had significantly higher levels of APRIL. Our results revealed that APRIL serum levels at time of surgery were associated with features of advanced disease and prognosis in rectal cancer patients, which strengthens the previously reported preclinical observation of increased APRIL levels correlating with disease progression.

Pre- and post-operative evaluation: percentages of circulating myeloid-derived suppressor cells in rectal cancer patients.

This study aims to explore whether pre-operative or post-operative percentages of circulating myeloid-derived suppressor cells (MDSC) have any correlations with clinicopathological parameters in patients with rectal cancer and have any predictive values for local recurrence and disease free survival. Lin-/HLADR-/CD11b+/CD33+ MDSCs were analyzed in the study. Blood samples before and after surgery were measured by flow cytometry to determine the MDSC percentages. Plasma arginase Ilevels were analyzed using an enzyme-linked immunosorbent assay. Digital rectal examination, abdominal ultrasonography, or computed tomography was performed every three months after surgery to monitor local recurrence. Prior to surgery, cancer patients presented with higher levels of circulating MDSC compared to healthy controls (medians of 3.89% and 0.57%, respectively). Seven days after operation, we observed an immediate increase in MDSC followed by adowntrend. Local recurrence was observed in 11 of 41 patients (26.8%) with stage I/II cancer and 11 of 23 patients (47.8%) with stage III cancer. Significantly higher percentages of MDSC were observed in patients who had local recurrence versus patients without local recurrence. Multivariate analysis further verified that the pre-operative level of MDSC was significantly associated with local recurrence (P=0.038). Therefore, our results indicate that pre-operative percentage of MDSC appears to be areliable prognostic marker for local recurrence and poor disease free survival in rectal cancer patients with curative resection. myeloid-derived suppressor cells, rectal cancer, plasma arginase I, local recurrence, disease free survival.

94. Treatment and survival of rectal cancer patients over the age of 80 years; a EURECCA international comparison

94. Treatment and survival of rectal cancer patients over the age of 80 years; a EURECCA international comparison

96. Differences in adjuvant chemotherapy administration for rectal cancer patients - a EURECCA international comparison

Background: Considerable debate exists on the role of adjuvant chemotherapy for rectal cancer patients after preoperative (chemo)radiation and TME surgery, and trials did not give a definitive answer so far. The aim of this large population-based international comparison, using country as instrumental variable, is to compare treatment strategies and survival in rectal cancer patients among seven European countries. This could lead to new insights on the value of adjuvant chemotherapy for rectal cancer patients

Fibroblast growth factor receptor 2 overexpression is predictive of poor prognosis in rectal cancer patients receiving neoadjuvant chemoradiotherapy

AimsNeoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is an increasingly used therapeutic strategy for advanced rectal cancer, but risk stratification and final outcomes remain suboptimal. Recently, the oncogenic role of...

Abstract 4897: Genetic variants and expression of AEG-1 in relation to clinical outcome and radiotherapy response in colorectal cancer patients and cell lines

Abstract Background: Colorectal cancer (CRC) is the third most common cancer in men and the second in woman worldwide. The therapy of CRC has been critically improved during the past two decades, but the treatment response varies significantly between different treatments and patients. Therefore it is of need to search for biomarkers for more suitable prognosis and treatment. The aim of this study was to investigate genetic variants of the astrocyte elevated gene-1 (AEG-1), its expression in CRC patient samples and colon cancer cell lines and the potential correlation to clinicopathological variables and treatment response. Materials and Methods: We analysed genetic variants and the mRNA and protein expression of AEG-1 in 593 CRC patient samples by direct Sanger sequencing, qPCR and immunohistochemistry. Of the patients, 158 rectal cancer patients were enrolled in the Swedish clinical trial of preoperative radiotherapy (RT). AEG-1 expression in response to γ-irradiation was analysed by Western blot in 5 colon cancer cell lines. We inhibited the AEG-1 expression by siRNA in the cell lines, and their survival was analysed after γ-irradiation. Results: By direct sequencing we found 29 variants, of which 12 were novel. Six of the variants were exonic and 23 intronic. The variant c.1353G&amp;gt;A, rs2331652 was found only in 4 samples and the variant c.1679-6 T&amp;gt;C in only one sample. In the cell lines KM12C, KM12SM and KM12L4a we found a deletion in exon 4 (c.595_598delAGAG). AEG-1 mRNA and protein expression revealed a significant increased AEG-1 expression in the primary tumors and metastases compared to the normal mucosa in all patient cohorts (p&amp;lt;0.006) and on the mRNA level a higher expression in tumors located in the rectum compared to tumors in the colon (p=0.047). In the rectal cancer patients from the Swedish trail of preoperative RT, a high AEG-1 expression correlated with a higher risk of distant recurrence and disease free survival (p=0.001 respectively) independently of the tumor stage, only in patients receiving preoperative RT. AEG-1 knock-down in the radioresistant cell lines KM12L4a, SW480 and SW620 resulted in reduction of the survival after radiation, but not in the radiosensitive cell lines KM12C and HCT116. The AEG-1 expression was up-regulated shortly after 2 Gy γ-radiation in KM12C, KM12L4a and SW480, but not in SW620 and HCT116. Conclusion: We found several novel AEG-1 variants. The AEG-1 expression at the mRNA and/or protein level was up-regulated in the primary tumour and metastases compared to the normal mucosa. Furthermore we showed for the first time that the AEG-1 expression is an independent prognostic factor for distant recurrence and disease-free survival in rectal cancer patients after treatment with preoperative RT. The cell line studies suggest AEG-1 as a promising radiosensitizing target for rectal cancer. Citation Format: Sebastian Gnosa, Veronika Patcha Brodin, Ivana Ticha, Gunnar Adell, Gunnar Arbman, Hong Zhang, Xiao-Feng Sun. Genetic variants and expression of AEG-1 in relation to clinical outcome and radiotherapy response in colorectal cancer patients and cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4897. doi:10.1158/1538-7445.AM2014-4897