Colon Cancer-specific Survival Research Articles

Comparison of deep learning models to traditional Cox regression in predicting survival of colon cancer: Based on the SEER database.

In this study, a deep learning algorithm was used to predict the survival rate of colon cancer (CC) patients, and compared its performance with traditional Cox regression. In this population-based cohort study, we used the characteristics of patients diagnosed with CC between 2010 and 2015 from the Surveillance, Epidemiology and End Results (SEER) database. The population was randomized into a training set (n=10596, 70%) and a test set (n=4536, 30%). Brier scores, area under the (AUC) receiver operating characteristic curve and calibration curves were used to compare the performance of the three most popular deep learning models, namely, artificial neural networks (ANN), deep neural networks (DNN), and long-short term memory (LSTM) neural networks with Cox proportional hazard (CPH) model. In the independent test set, the Brier values of ANN, DNN, LSTM and CPH were 0.155, 0.149, 0.148, and 0.170, respectively. The AUC values were 0.906 (95% confidence interval [CI] 0.897-0.916), 0.908 (95% CI 0.899-0.918), 0.910 (95% CI 0.901-0.919), and 0.793 (95% CI 0.769-0.816), respectively. Deep learning showed superior promising results than CPH in predicting CC specific survival. Deep learning showed potential advantages over traditional CPH models in terms of prognostic assessment and treatment recommendations. LSTM exhibited optimal predictive accuracy and has the ability to provide reliable information on individual survival and treatment recommendations for CC patients.

Role of adjuvant radiotherapy in resected T4aN0 colon cancer

For T4 colon cancer, multiple studies point to a benefit of adjuvant radiotherapy (RT). However, the evidence on whether and how adjuvant RT benefits survival outcomes in patients with T4aN0 disease is relatively scarce. This study sought to investigate the overall survival (OS) and colon cancer-specific survival (CSS) of patients with T4aN0 colon cancer defined by the American Joint Committee on Cancer (AJCC) 7th staging manual colon cancer treated with and without adjuvant RT, using the Surveillance, Epidemiology, and End Results (SEER) database. Patients aged over 20 years with T4aN0 disease defined by AJCC7th were eligible for inclusion. The propensity score matching (PSM) method was utilized to balance the baseline characteristics between those with and without adjuvant RT. Univariate and multivariable Cox regression analyses were conducted to determine the association between the study variables, OSS, and CCS, presented as hazard ratios (HRs) and 95% confidence intervals (CIs). Data of 3515 patients (with RT: 88; without RT: 3427) during 2010–2017 were extracted in the SEER*Stat database. After PSM, 440 patients (with RT: 88, without RT: 352) were included in the subsequent analyses. After controlled for relevant confounders including chemotherapy, the results showed that OS (adjusted HR [aHR] = 1.27, 95% CI = 0.81–1.78) and CSS (aHR = 1.54, 95% CI = 0.99–2.41) were not significantly different between patients who received adjuvant RT or not. In conclusion, no statistically significant difference in survival between patients treated with and without adjuvant radiation. Future studies evaluating the role of adjuvant RT for preventing recurrence in this specific patient subgroup are needed.

Prognostic role of detailed colorectal location and tumor molecular features: analyses of 13,101 colorectal cancer patients including 2994 early-onset cases.

The pathogenic effect of colorectal tumor molecular features may be influenced by several factors, including those related to microbiota, inflammation, metabolism, and epigenetics, which may change along colorectal segments. We hypothesized that the prognostic association of colon cancer location might differ by tumor molecular characteristics. Utilizing a consortium dataset of 13,101 colorectal cancer cases, including 2994 early-onset cases, we conducted survival analyses of detailed tumor location stratified by statuses of microsatellite instability (MSI), CpG island methylator phenotype (CIMP), and KRAS and BRAF oncogenic mutation. There was a statistically significant trend for better colon cancer-specific survival in relation to tumor location from the cecum to sigmoid colon (Ptrend = 0.002), excluding the rectum. The prognostic association of colon location differed by MSI status (Pinteraction = 0.001). Non-MSI-high tumors exhibited the cecum-to-sigmoid trend for better colon cancer-specific survival [Ptrend < 0.001; multivariable hazard ratio (HR) for the sigmoid colon (vs. cecum), 0.80; 95% confidence interval (CI) 0.70-0.92], whereas MSI-high tumors demonstrated a suggestive cecum-to-sigmoid trend for worse survival (Ptrend = 0.020; the corresponding HR, 2.13; 95% CI 1.15-3.92). The prognostic association of colon tumor location also differed by CIMP status (Pinteraction = 0.003) but not significantly by age, stage, or other features. Furthermore, MSI-high status was a favorable prognostic indicator in all stages. Both detailed colonic location and tumor molecular features need to be accounted for colon cancer prognostication to advance precision medicine. Our study indicates the important role of large-scale studies to robustly examine detailed colonic subsites in molecular oncology research.

The Prognostic Value of Adjuvant Chemotherapy in Colon Cancer With Solitary Tumor Deposit.

PurposeThe aim of this study is to investigate the survival benefit of adjuvant chemotherapy in patients with colon cancer with the solitary tumor deposit (TD).MethodsThe primary study outcomes used in this study were colon cancer–specific survival (CSS) and overall survival (OS). The differences of the distribution of categorical variables in patients with colon cancer with the solitary TD according to adjuvant chemotherapy administration were tested using the Pearson’s chi-square test. The Kaplan–Meier method was utilized to evaluate CSS and OS. Hazard ratio (HR) and 95% confidence interval (CI) were calculated on the basis of Cox regression models to assess the prognostic value of different demographic and clinicopathological characteristics.ResultsA total of 877 patients with TanyN1cM0 colon cancer with solitary TD were identified in our analysis. It was found that OS (75.4% vs. 42.8% for 5-year OS rate, p < 0.001) and CSS (82.9% vs. 69.3% for 5-year CSS rate, p < 0.001) of patients with colon cancer with adjuvant chemotherapy administration were significantly better than those without adjuvant chemotherapy administration. Multivariate Cox survival analyses revealed that the overall and colon cancer–specific mortality risks of patients with adjuvant chemotherapy administration were decreased by 64.4% (HR = 0.356, 95% CI = 0.265–0.479, p < 0.001) and 57.4% (HR = 0.426, 95% CI = 0.286–0.634, p < 0.001) compared with those without adjuvant chemotherapy administration, respectively.ConclusionsAdjuvant chemotherapy administration could significantly improve OS and CSS in patients with colon cancer with the solitary TD. This is the first study to investigate and demonstrate the survival benefit of adjuvant chemotherapy in patients with colon cancer with the solitary TD.

Risk of colon cancer-related death in people who had cancer in the past.

The rate of second primary malignancies (SPM) is gradually increasing. Yet, the risk of death from primary cancer vs. SPM is still not well understood. In this study, we investigated the survival of patients with colorectal cancer (as SPM) who had cancer in the past (prior cancer) and the risk factors of SPM death in this population. Based on the Surveillance, Epidemiology, and End Results (SEER) database, we identified 1866 colon cancer patients with prior cancer in our main cohort and 43,959 colon cancer patients, including 37,440 patients with colon cancer as only malignancy and 6519 patients with colon cancer as subsequent colon cancer (SCC), in a second cohort and 3429 colon cancer patients, including 2371 patients with prior colon cancer (PCC) and 1058 patients with colon cancer as SPM, in a third cohort. After propensity score matching, 6519 pairs of subjects were identified in second cohort. Patients with prior prostate and breast cancer had a higher risk of developing colon cancer compared to those with gastrointestinal cancer. Also, colon cancer patients with different prior cancer had different survival rates. Furthermore, except for prior lung cancer (52.78 vs. 25.93%), most subjects died due to colon cancer complications. The ratio of colon cancer deaths to prior cancer deaths in patients with a low stage and high stage was 1.51 and 6.64, respectively. In addition, colon cancer-specific survival (CSS) and OS rates were significantly lower in subjects with colon cancer as the SPM than in those with PCC. Also, compared with PCC, SPM was associated with OS and CSS with HR 1.59 (95 CI 1.43-1.78) and HR 2.00 (95% CI 1.70-2.36). Furthermore, compared with only colon cancer, SCC was associated with OS and CSS with HR 1.23 (95 CI 1.17-1.29) and HR 1.13 (95% CI 1.06-1.21). Prior cancer was found to have an adverse impact on OS in patients with colon cancer (secondary cancer), most of whom died due to colon cancer as secondary cancer itself rather than prior cancer. Early detection and treatment strategies should be investigated in this population.

ASO Visual Abstract: Predicting Colon Cancer-Specific Survival for the Asian Population Using National Cancer Registry Data from Taiwan

ASO Visual Abstract: Predicting Colon Cancer-Specific Survival for the Asian Population Using National Cancer Registry Data from Taiwan

Predicting Colon Cancer-Specific Survival for the Asian Population Using National Cancer Registry Data from Taiwan.

Colon cancer is the third most incident and life-threatening cancer in Taiwan. A comprehensive survival prediction system would greatly benefit clinical practice in this area. This study was designed to develop an accurate prognostic model for colon cancer patients by using clinicopathological variables obtained from the Taiwan Cancer Registry database. We analyzed 20,218 colon cancer patients from the Taiwan Cancer Registry database, who were diagnosed between 2007 and 2015, were followed upuntil December 31, 2017, and had undergone curative surgery. We proposed two prognostic models, with different combinations of predictors. The first model used only traditional clinical features. The second model included several colon cancer site-specific factors (circumferential resection margin, perineural invasion, obstruction, and perforation), in addition to the traditional features. Both prediction models were developed by using a Cox proportional hazards model. Furthermore, we investigated whether race is a significant predictor of survival in colon cancer patients by using Model 1 on the Surveillance, Epidemiology, and End Results (SEER) cancer registry dataset. The proposed models displayed a robust prediction performance (all Harrell's c-index >0.8). For both the calibration and validation steps, the differences between the predicted and observed mortality were mostly less than 5%. The prediction model (Model 1) is an effective predictor of survival regardless of the ethnic background of patients and can potentially help to provide better prediction of colon cancer-specific survival outcomes, thus allowing physicians to improve treatment plans.

Preoperative multidisciplinary team assessment is associated with improved survival in patients with locally advanced colon cancer; a nationwide cohort study in 3157 patients

IntroductionMultidisciplinary team (MDT) assessment is associated with improved survival in locally advanced rectal cancer, but the effect of an MDT assessment on survival in locally advanced colon cancer has not been reported. The aim of this national population-based cohort study was to establish if preoperative MDT assessment affects prognosis in patients with primary locally advanced colon cancer. Material and methodsAll patients in Sweden with locally advanced colon cancer, without metastatic disease, who underwent an elective colon resection between 2010 and 2017 were identified through the Swedish Colorectal Cancer Registry (SCRCR), and the cohort was linked to national registers. Data on patient characteristics, preoperative staging, surgical procedures, recurrence and survival were collected from SCRCR. The association between MDT assessment and colon cancer-specific survival was evaluated using Kaplan-Meier survival curves and Cox proportional hazards models. The multivariable analysis was adjusted for sex, age, ASA grade, CCI, time period, pN, region and preoperative MDT. ResultsMDT assessment was performed in 2663 patients (84.4%) of 3157 eligible patients. The 3-year colon cancer-specific survival was higher following MDT, compared with no MDT assessment (80% versus 68%). MDT assessment was independently associated with reduced colon cancer-specific mortality (HR 0.70, 0.57–0.84 95% CI). ConclusionPreoperative MDT assessment is associated with an improved long-term survival in patients with locally advanced colon cancer and should be mandatory in patients with suspected locally advanced colon cancer.

Association of tumor size with prognosis in colon cancer: A Surveillance, Epidemiology, and End Results (SEER) database analysis

BackgroundThus far, the association of tumor size with prognosis in colon cancer has not been considered and has remained unclear. This study, therefore, aimed to investigate the association between tumor size as a continuous variable and prognosis in colon cancer using Cox models with restricted cubic splines. MethodsUsing the Surveillance, Epidemiology, and End Results database, we selected 128,369 patients with colon cancer who underwent surgery. Overall survival and colon cancer-specific survival were separately analyzed, and tumor size was separately evaluated as a continuous variable and a categorical variable. To investigate the relationship after adjusting for covariates, we used the proportional hazards models. The restricted cubic splines model was used to determine the presence of nonlinear or linear association and flexibly visualize the association. ResultsThe adjusted covariate model showed that the hazard ratio of colon cancer rapidly increased with a tumor size of 4 cm and slowly increased with a tumor size larger than 4 cm. When tumor size was analyzed as a categorical variable, the multivariable-adjusted model demonstrated a nearly linear relationship between tumor size and hazard ratio regardless of overall survival or cancer-specific survival, and the hazard ratio of group 5 (4.1–5 cm) was nearly a turning point. Subgroup analysis with respect to lymph node metastasis showed that the relationship between tumor size and prognosis in colon cancer was evident in lymph node metastasis. ConclusionThere was a strong negative relationship between tumor size and prognosis in colon cancer. However, when tumor size was less than 4 cm, the relationship between tumor size and prognosis was steep compared with that when tumor size was larger than 4 cm, especially in lymph node metastasis.

Outcomes of non-metastatic colon cancer patients in relationship to socioeconomic status: an analysis of SEER census tract-level socioeconomic database.

To evaluate the outcomes of non-metastatic colon cancer patients in relation to the socioeconomic status (SES) at diagnosis based on the Surveillance, Epidemiology, and End Results (SEER) census tract level-SES database. SEER SES census tract level database represents a specially designed database to integrate different aspects of SES among cancer patients. It reports a composite SES index for each patient. Patients were then stratified into three SES groups. Patients with a non-metastatic colon cancer diagnosis, diagnosed (2004-2015), and who were included in this specialized database were included in the current study. Multivariate Cox regression analysis was used to assess the impact of SES index on colon cancer-specific survival. A total of 80,121 patients with non-metastatic colon cancer were included in the current study. Comparing patients in the lower SES group with patients in the higher SES group, patients with lower SES were more likely to have a younger age at presentation (P < 0.001), black race (P < 0.001) and more advanced stage at presentation (P < 0.001). The impact of the SES on colon cancer-specific survival was evaluated through multivariate Cox regression analysis adjusted for age, sex, race, stage, and colon cancer side. Lower SES was associated with worse colon cancer-specific survival (hazard ratio for group 1 versus group 3: 1.257; 1.190-1.328; P < 0.001). Interaction testing between race (black race versus white race) and SES was non-significant (P = 0.932). Lower SES is associated with worse colon cancer-specific survival among non-metastatic colon cancer patients.

Timing of first surveillance colonoscopy in stage I colon cancer patients and the association with colon cancer-specific survival.

618 Background: Surveillance colonoscopy following curative surgery in stage I colon cancer patients is controversial. This study was conducted to assess the relationship between timing of first surveillance colonoscopy and 5-year colon cancer-specific survival. Methods: This was a retrospective cohort study of the Surveillance, Epidemiology, and End Results database combined with Medicare claims. Stage I colon cancer patients (66-84 years of age) were categorized according to receipt of first colonoscopy following cancer-directed surgery as: Year 1, Year 2, Year 3, and No Colonoscopy within 3 years of surgery. Propensity score weighting was used to balance covariates. Cox regression was used to obtain hazard ratios for the relative risk of 5-year colon cancer-specific death, adjusted survival estimates, and the number needed to treat (NNT) with colonoscopy in Year 1 to prevent a colon cancer-specific death in the other groups. Results: There were 8,494 stage I colon cancer patients available for analysis. Regarding 5-year colon cancer-specific mortality, compared to Year 1 patients, the No Colonoscopy group experienced 2.2 times the risk of colon cancer-specific death (HR, 2.23; 95% CI, 1.38 to 3.61). Those who received ≥ 1 additional colonoscopies in the two years following their initial assessment experienced a significant 73% decreased risk of death (HR, 0.27; 95% CI, 0.16 to 0.45). Delaying colonoscopy (Years 2 &amp; 3) did not result in a statistically significant increased risk of death. Although the absolute difference in 5-year adjusted survival was small, if all patients in the No Colonoscopy group received a colonoscopy in Year 1, 46.2% (n = 49.9) of the 108 colon cancer deaths that occurred in this group could have been prevented. Conclusions: Although stage I colon cancer patients have a good prognosis, patients who received colonoscopy within one year of cancer-directed surgery experienced significantly better survival than patients who did not receive colonoscopy within 3 years of surgery. The results of this study justify efforts to ensure that stage I colon cancer patients receive colonoscopic surveillance testing approximately 1 year following cancer-directed surgery.

Gender Disparities in Short-Term and Long-Term Colon Cancer Specific Survival

Gender Disparities in Short-Term and Long-Term Colon Cancer Specific Survival

Polypectomy versus surgery in early colon cancer: size and location of colon cancer affect long-term survival.

The colon cancer survival rate is significantly affected by location, stage, and size of the cancer. Polypectomy was shown be as equally effective as surgery in early-stage colon cancer, but there have been no established clinical guidelines in the management of colon cancer based on the size of the polyp or the tumor location. The aim of our study was to assess the early-stage colon cancer-specific survival rate in patients who underwent endoscopic polypectomy versus surgery, based on size and location of tumor in early-stage colon cancer. This is a population-based nationwide study in the USA. Of 13,157 patients, 15.5% underwent endoscopic treatment and 84.5% underwent surgical therapy. For early cancer tumors located in the left colon, polypectomy yielded comparable 5-year survivals to surgery irrespective of size of the tumors. Five-year early cancer-specific survivals were similar for tumors located in the right colon that were < 20mm in size (94.5 vs 94.3%, p value = 0.94). However, tumors > 20mm in size that were located in the right colon had better survivals when treated surgically compared to those treated with polypectomy (20-39mm: 91.8 vs 74.2%; ≥ 40mm: 92.4 vs 60%, both p values < 0.01). Similar results were obtained on propensity score analysis. Polypectomy was as effective as surgical therapy for small tumors. For larger tumors, surgical therapy is better than polypectomy for right-sided tumors, but both are equally effective for left-sided tumors.

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.

Right colon cancer: Left behind

IntroductionPrognosis of colon cancer (CC) has steadily improved during the past three decades. This trend, however, may vary according to proximal (right) or distal (left) tumor location. We studied if improvement in survival was greater for left than for right CC. MethodsWe included all CC recorded at the Geneva population-based registry between 1980 and 2006. We compared patients, tumor and treatment characteristics between left and right CC by logistic regression and compared CC specific survival by Cox models taking into account putative confounders. We also compared changes in survival between CC location in early and late years of observation. ResultsAmong the 3396 CC patients, 1334 (39%) had right-sided and 2062 (61%) left-sided tumors. In the early 1980s, 5-year specific survival was identical for right and left CCs (49% vs. 48%). During the study period, a dramatic improvement in survival was observed for patients with left-sided cancers (Hazard ratio [HR]: 0.42, 95% confidence interval [CI]: 0.29–0.62, p < 0.001) but not for right CC patients (HR: 0.76, 95% CI: 0.50–1.14, p = 0.69). As a consequence, patients with distal CC have a better outcome than patients with proximal CC (HR for left vs. right CC: 0.81, 95% CI: 0.72–0.90, p < 0.001). ConclusionOur data indicate that, contrary to left CC, survival of patients with right CC did not improve since 1980. Of all colon cancer patients, those with right-sided lesions have by far the worse prognosis. Change of strategic management in this subgroup is warranted.

LINE-1 hypomethylation in normal colon mucosa is associated with poor survival in Chinese patients with sporadic colon cancer.

Genetic and epigenetic pathways are not independent in colorectal cancer (CRC) carcinogenesis. We aimed to determine the influence of various molecular features on Chinese patients' colon cancer-specific survival (CCSS). Various genetic and epigenetic modifications were detected in paired tumor and normal mucosa tissue samples. The prognostic variables regarding patient CCSS were determined. Overall, 127 patients, including 83 males and 44 females, completed a median follow-up of 65 (3-85) months. A mean LINE-1 methylation rate of 64.62% (range, 9.45-86.93) was observed. Hypermethylation at the hMLH1 gene promoter was detected in 26 (20.47%) patients. KRAS was mutated in 52 (40.94%) patients. Sixteen (12.60%) patients were confirmed as microsatellite instability (MSI)-High, and 76 (59.84%) were found to have loss of heterozygosity at 18q. The LINE-1 methylation level, MSI status, perineural invasion and distant metastases were confirmed as independent prognostic factors for patient CCSS. A stratified survival analysis further revealed that certain subgroups of patients with LINE-1 hypomethylation had significantly worse survival (all p < 0.05). Our data revealed that both genetic and epigenetic abnormalities can concurrently exist during colonic tumorigenesis. As a global epigenetic change, LINE-1 hypomethylation in normal colon mucosa might be associated with a worse outcome in certain Chinese patients with colon cancer.

Type 2 diabetes mellitus is associated with increased mortality in Chinese patients receiving curative surgery for colon cancer.

We investigated the association between diabetes mellitus (DM) and the prognosis of patients with early colon cancer who had undergone curative surgery. From three national databases of patients in Taiwan, we selected a cohort of colon cancer patients who had been newly diagnosed with stage I or stage II colon cancer between January 1, 2004 and December 31, 2008 and had undergone curative surgery. We collected information regarding DM (type 2 DM only), the use of antidiabetic medications, other comorbidities, and survival outcomes. The colon cancer-specific survival (CSS) and the overall survival (OS) were compared between patients with and without DM. We selected 6,937 colon cancer patients, among whom 1,371 (19.8%) had DM. The colon cancer patients with DM were older and less likely to receive adjuvant chemotherapy but had a similar tumor stage and grade, compared with colon cancer patients without DM. Compared with colon cancer patients without DM, patients with DM had significantly shorter OS (5-year OS: 71.0% vs. 81.7%) and CSS (5-year CSS: 86.7% vs. 89.2%). After adjusting for age, sex, stage, adjuvant chemotherapy, and comorbidities in our multivariate analysis, DM remained an independent prognostic factor for overall mortality (adjusted hazards ratio: 1.32, 95% confidence interval: 1.18-1.49), but not for cancer-specific mortality. Among the colon cancer patients who had received antidiabetic drug therapy, patients who had used insulin had significantly shorter CSS and OS than patients who had not. Among patients who receive curative surgery for early colon cancer, DM is a predictor of increased overall mortality.

Solitary lymph node metastasis is a distinct subset of colon cancer associated with good survival: a retrospective study of surveillance, epidemiology, and end-results population-based data.

BackgroundColon cancer with lymph node metastases has been considered as advanced stage and to have poor survival. We postulated that patients with solitary lymph node metastasis are a distinct subset with better colon cancer-specific survival than those with multiple lymph node metastases.MethodsIn this retrospective study, we searched Surveillance, Epidemiology, and End-Results (SEER) population-based data and identified 86,674 patients who had been diagnosed with colon cancer without distant metastases and with less than three metastatic nodes between 1991 and 2005. We divided lymph node status into three subgroups: pN0, pN1a, and pN1b and obtained 5-year colon cancer-specific survival for each pT stage. We used Kaplan–Meier and multivariate Cox regression models to assess correlations between risk factors and survival outcomes.ResultsAnalysis of SEER data confirmed that patients with solitary lymph node metastases had better 5-year cancer-specific survival than pN1b according to both univariate and multivariate analysis. This finding was confirmed by further analyses in five pT subgroups. Cancer-specific survival of patients with pT1-2N1a was comparable to that of those with pIIA but higher than those with pIIB. In addition, survival of patients with pT3-4aN1a was better than those with pIIC.ConclusionColon cancer patients with solitary lymph node metastasis are a distinct subset with a favorable prognosis; full consideration should be given to this in clinical practice.

Survival benefit associated with the number of chemotherapy/biologic treatment lines in 5,129 metastatic colon cancer patients.

559 Background: The purpose of this study was to investigate the association between multiple chemotherapy/biologic treatment lines and survival among patients diagnosed with metastatic colon cancer (mCC). Methods: Patients aged 66 to 105 years old diagnosed with mCC between 2003 and 2007 were selected for analysis from the Surveillance, Epidemiology and End Results SEER-Medicare data to determine the association between chemotherapy/biologic treatment lines and survival. We examined the survival benefits using Cox proportional-hazards regressions with inverse probability weighting method to adjust for the probability of receiving treatment lines. Results: Patients with no chemotherapy/biologic treatment had an adjusted median survival time of 6.8 months. Each chemotherapy/biologic treatment line received was associated with longer adjusted median survival times: 11.9 months, 23.2 months and 26.4 months for receipt of first-line treatment only, second-line treatment and subsequent treatment, respectively. Colon cancer-specific mortality hazard ratios (HRs) were 0.637, 0.391 and 0.350 (p&lt;0.001 for each) for first-line, second-line and subsequent treatments, respectively. Overall mortality hazard ratios were 0.604, 0.398 and 0.364 (p&lt;0.001 for each) for first-line, second-line and subsequent treatments, respectively. Compared to receiving only first-line treatment, proceeding to second-line treatment was associated with longer colon cancer-specific survival (HR=0.614, p&lt;0.001) and longer overall survival (HR=0.659, p&lt;0.001). Patients with a low-graded tumor had longer colon cancer-specific and overall survival (HR=0.746, p&lt;0.001; HR=0.762, p&lt;0.001, respectively) and lived 5.6 months longer. Factors associated with shorter survival were a higher age category and being female. Conclusions: Among mCC patients who survived at least 3 months from diagnosis, each chemotherapy/biologic treatment line was independently associated with significantly longer survival. Proceeding from first-line to second-line therapy or having a low-graded tumor was also associated with longer survival. Proceeding from second-line third-line therapy showed neither benefit nor harm.

PD-0005 - Prognostic Biomarkers in a Series of Stage II Colon Cancer

Background: Different clinico-pathological factors are used to define a group of patients with high-risk stage II colon cancer that may benefit from adjuvant chemotherapy. Moreover, several molecular markers, such as microsatellite instability (MSI) and BRAF, have been widely investigated as putative prognostic factors. Recently a high stroma component (tumors with mesenchymal phenotype consistent with epithelial to mesenchymal transition) has also been associated with poor outcome.Methods: Between 1996 and 2006 data from patients diagnosed with colorectal cancer at Hospital Universitari Bellvitge (HUB) and its referral comprehensive cancer center, Institut Català d'Oncologia (ICO)/ L'Hospitalet, were prospectively included in a database. Formalin-fixed paraffin-embedded tissue samples from 432 stage II colon cancer patients operated at HUB were included in the molecular analyses. MSI status, BRAF V600E mutation and tumor-stroma ratio in tumor samples were analyzed. MSI status was assessed by the analysis of 5 mononucleotide repeat markers (BAT-25, BAT-26, NR-21, NR-24 and MONO-27). BRAF V600E mutation was analyzed by single strand conformation polymorphism technique. Tumor-stroma ratio was analyzed by immunohistochemistry. Associations between molecular factors and clinical features were assessed by Chi-Squared (X2) tests. A Cox regression model was used to evaluate the Relapse Free Survival (RFS) and the Colon Cancer specific Survival.Results: MSI status could be determined by genotyping in 350 tumor samples. 48 patients (14%) had MSI high (MSI-H) tumors and 302 (86%) had microsatellite stable (MSS) tumor. BRAF status could be determined in 380 tumor samples. 58 cases (15%) were BRAF mutated tumors and 322 (85%) were BRAF wild type tumors. Tumor-stroma ratio was analyzed in 407 cases. 176 tumors (43%) had more than 50% intra-tumor stroma and were classified as stroma-high. MSI-H tumors were significantly located in the right colon (X2 p-value = 1.03e-5), were poorly differentiated (X2 p-value = 0.003) and had more than 12 lymph nodes resected (X2 p-value = 0.037). MSI-H tumors were associated with BRAF mutation (X2 p-value = 0.02) and stroma-low (X2 p-value = 0.0005). When a molecular prognostic risk classification was performed, patients with MSI-H and stroma-low suggested a low risk of relapse comparing to MSI-H/stroma-high, MSS/stroma-low and MSS/stroma-high (Hazard Ratio = 3.15; 95% CI, 0.76 - 13.1, p-value = 0.0602).Conclusion: MSI-H tumors are typically poorly differentiated, located in the right colon and have BRAF mutation as well as low intra-tumor stroma. Our results suggest that low-stroma could partly explain prognosis in patients with MSI-H stage II tumors. Background: Different clinico-pathological factors are used to define a group of patients with high-risk stage II colon cancer that may benefit from adjuvant chemotherapy. Moreover, several molecular markers, such as microsatellite instability (MSI) and BRAF, have been widely investigated as putative prognostic factors. Recently a high stroma component (tumors with mesenchymal phenotype consistent with epithelial to mesenchymal transition) has also been associated with poor outcome. Methods: Between 1996 and 2006 data from patients diagnosed with colorectal cancer at Hospital Universitari Bellvitge (HUB) and its referral comprehensive cancer center, Institut Català d'Oncologia (ICO)/ L'Hospitalet, were prospectively included in a database. Formalin-fixed paraffin-embedded tissue samples from 432 stage II colon cancer patients operated at HUB were included in the molecular analyses. MSI status, BRAF V600E mutation and tumor-stroma ratio in tumor samples were analyzed. MSI status was assessed by the analysis of 5 mononucleotide repeat markers (BAT-25, BAT-26, NR-21, NR-24 and MONO-27). BRAF V600E mutation was analyzed by single strand conformation polymorphism technique. Tumor-stroma ratio was analyzed by immunohistochemistry. Associations between molecular factors and clinical features were assessed by Chi-Squared (X2) tests. A Cox regression model was used to evaluate the Relapse Free Survival (RFS) and the Colon Cancer specific Survival. Results: MSI status could be determined by genotyping in 350 tumor samples. 48 patients (14%) had MSI high (MSI-H) tumors and 302 (86%) had microsatellite stable (MSS) tumor. BRAF status could be determined in 380 tumor samples. 58 cases (15%) were BRAF mutated tumors and 322 (85%) were BRAF wild type tumors. Tumor-stroma ratio was analyzed in 407 cases. 176 tumors (43%) had more than 50% intra-tumor stroma and were classified as stroma-high. MSI-H tumors were significantly located in the right colon (X2 p-value = 1.03e-5), were poorly differentiated (X2 p-value = 0.003) and had more than 12 lymph nodes resected (X2 p-value = 0.037). MSI-H tumors were associated with BRAF mutation (X2 p-value = 0.02) and stroma-low (X2 p-value = 0.0005). When a molecular prognostic risk classification was performed, patients with MSI-H and stroma-low suggested a low risk of relapse comparing to MSI-H/stroma-high, MSS/stroma-low and MSS/stroma-high (Hazard Ratio = 3.15; 95% CI, 0.76 - 13.1, p-value = 0.0602). Conclusion: MSI-H tumors are typically poorly differentiated, located in the right colon and have BRAF mutation as well as low intra-tumor stroma. Our results suggest that low-stroma could partly explain prognosis in patients with MSI-H stage II tumors.