Stage IIA Colon Cancer Research Articles

Factors Affecting Recurrence and Survival in Stage IIA Colon Cancer Patients.

Our study delves into the intricate interplay of risk factors and the strategic selection of adjuvant therapy, scrutinizing their influence on recurrence and survival outcomes in stage IIA (T3N0M0) colon cancer patients. The study examined the medical records of patients who underwent surgery for stage IIA colon cancer. Identification of stage IIA (pT3N0M0) colon cancer involved a comprehensive review of postoperative clinical records and histological reports. Parameters such as demographic data, tumor characteristics, microsatellite instability status, tumor locations, recurrence risk factors, preoperative carcinoembryonic antigen levels, and adjuvant treatments were systematically evaluated. In our study involving 220 patients, 138 were male (62.7%), with a median age of 62 years and a median body mass index of 25.1 kg/m2. In the patient group without risk factors, no statistically significant difference was detected in disease-free survival (DFS) rates between those who received treatment and those who did not (p = 0.546). DFS rates of patients with >1 risk factor were statistically significantly lower than those with a single risk factor (p = 0.017). In patients with >1 risk factor, the DFS of those who did not receive adjuvant treatment was significantly lower than those who received adjuvant treatment (p < 0.001). In the patient group with recurrence, when adjuvant treatments were considered, recurrence was significantly higher in the group receiving capecitabine (p = 0.01). The decision for adjuvant chemotherapy in stage IIA colon cancer patients involves careful consideration of various parameters and risk factors. The evolving landscape of research may refine recommendations, ensuring optimal treatment outcomes while minimizing unnecessary toxicity.

Complete Obstruction, a Real Risk Factor: A Comprehensive Study on Obstruction in Stage IIA Colon Cancer With Propensity Score Matching Analysis

MicroabstractThis study evaluates the prognostic significance of obstructions in stage IIA colon cancer, distinguishing between partial and complete obstructions. It employs a retrospective review of 1914 patients with propensity score matching to analyze oncologic outcomes. Findings reveal complete obstruction as a significant risk factor for poorer outcomes, emphasizing the necessity for further research to refine treatment strategies, particularly regarding the efficacy of adjuvant chemotherapy across obstruction types. BackgroundThis study examined the prognostic impact of obstructions in stage IIA colon cancer. The analysis specifically differentiated partial and complete obstructions, analyzing their distinct influences of both on oncologic outcomes. Materials and MethodsA retrospective review was conducted of stage IIA colon cancer cases with the presence of an obstruction. Patients were stratified by whether it was partial or complete based on the severity of obstruction. Propensity score matching was employed to control for confounders. ResultsAmong 1914 consecutive patients diagnosed with stage IIA colon cancer, 758 patients (597 patients with partial obstruction, 161 patients with complete obstruction) exhibited obstruction, while 1156 patients had no obstruction. The median follow-up period was 126 months. Complete obstruction was associated with poorer disease-free survival (Hazard ratio (HR) = 1.785, P < .001) and overall survival (HR = 1.853, P = .001). This trend persisted after propensity score matching, patients with complete obstruction showing a worsened disease-free survival (HR = 1.666, P = .028) and overall survival (HR = 1.732, P = .041). Adjuvant chemotherapy showed improved outcomes overall, but its efficacy varied across obstruction types. ConclusionDifferentiating between complete and partial obstructions in stage IIA colon cancer is an important clinical distinction, as our findings suggest that complete obstruction is a significant risk factor for poorer oncologic outcomes. While adjuvant chemotherapy generally improves prognosis in stage IIA colon cancer, the correlation of obstruction type with its efficacy remains uncertain, necessitating further research to refine treatment strategies.

Phase II results of circulating tumor DNA as a predictive biomarker in adjuvant chemotherapy in patients with stage II colon cancer: NRG-GI005 (COBRA) phase II/III study.

5 Background: For patients (pts) with colon cancer (CC), the detection of circulating tumor DNA (ctDNA) is associated with persistent disease after resection and outperforms traditional clinical and pathological features in prognosticating recurrence risk. We hypothesized that for pts with low-risk stage II CC, a positive ctDNA status after resection may identify those who benefit from adjuvant chemotherapy. Methods: In this prospective phase II/III clinical trial, pts with resected stage II CC without traditional high risk features and whom the evaluating oncologist deems suitable for active surveillance (i.e., not needing adjuvant chemotherapy) were randomized 1:1 to two arms: standard-of-care/observation (Arm A), or ctDNA assay directed therapy (Arm B). Postoperative blood was analyzed for ctDNA with the Guardant LUNAR assay, covering CC-relevant mutations and CC-specific methylation profiling. Arm B pts with ctDNA detected were treated with 6 mos of adjuvant (CAPOX or FOLFOX) chemotherapy. Primary endpoint for the phase II study was clearance of ctDNA at the 6-mo timepoint. A 1-sided Fisher exact test was used to compare ctDNA clearance between Arm A and Arm B among the first 16 pts with ctDNA detected at baseline. If p&gt;.35, the study would be stopped for futility of ctDNA clearance but would otherwise continue to phase III if p≤.35. We present the results of the pre-planned phase II analysis. Results: 635 pts were randomized (Arm A: 318; Arm B: 317). One pt with ctDNA detected in Arm B declined protocol-directed chemotherapy but was included in the intention to treat analysis. Among the first 16 pts with ctDNA detected at baseline for the primary endpoint analysis, clearance of ctDNA after 6 mos was observed in 3/7 pts (43%, 95% CI 10-82%) in the control arm and in 1/9 pts (11%, 95% CI 0.3-48%) in the experimental arm after chemotherapy (p=.98). There were no unanticipated toxicities in those treated with chemotherapy. Conclusions: The phase II endpoint was not met and further enrollment has been halted based upon pre-specified study stopping rules utilizing the original assay. No improvement in ctDNA clearance was observed after 6 mos of chemotherapy for pts with ctDNA detected following resection of stage IIA CC. Future trials evaluating ctDNA as an integral biomarker for minimal residual disease determination must account for assay specificity in this pt population. Support: U10CA180868, -180822; UG1CA189867; Guardant Health. Clinical trial information: NCT04068103 .

Benefit of Uracil-Tegafur Used as a Postoperative Adjuvant Chemotherapy for Stage IIA Colon Cancer.

Background and Objectives: Postoperative adjuvant therapy with uracil and tegafur (UFT) is often used for stage II colon cancer in Japan, but a limited number of studies have investigated the effects of UFT in these patients. Materials and Methods: We conducted a population-based cohort study in patients with resected stage II colon cancer comparing the outcomes after postoperative adjuvant chemotherapy with UFT with an observation-only group. The data were collected from the Taiwan National Health Insurance Research Database from 2000 to 2015. The outcomes of the study were disease-free survival (DFS) and overall survival (OS). The hazard ratios (HRs) were calculated using multivariate Cox proportional hazard regression models. Results: No differences in the DFS and OS were detected between the UFT (1137 patients) and observation (2779 patients) cohorts (DFS: adjusted HR 0.702; 95% confidence interval (CI) 0.489-1.024; p = 0.074) (OS: adjusted HR 0.894; 95% CI 0.542-1.186; p = 0.477). In the subgroup analyses of the different substages, UFT prolonged DFS in patients with stage IIA colon cancer (adjusted HR 0.652; 95% CI 0.352-0.951; p = 0.001) compared with DFS in the observation cohort, but no differences in the OS were detected (adjusted HR 0.734; 95% CI 0.475-1.093; p = 0.503). Conclusions: Our results show that DFS improved significantly in patients with stage IIA colon cancer receiving UFT as a postoperative adjuvant chemotherapy compared with DFS in the observation group.

Adjuvant chemotherapy benefits on patients with elevated carcinoembryonic antigen in stage IIA colon cancer: a SEER-based analysis.

Indications for adjuvant chemotherapy in stage IIA (T3N0M0) colon cancer are still controversial. The purpose of this study was to evaluate the prognostic value of elevated carcinoembryonic antigen (CEA) levels for cancer-specific survival (CSS) and overall survival (OS) in patients with stage IIA colon cancer. We aimed to examine the impact of adjuvant chemotherapy on OS in stage IIA colon cancer patients with elevated CEA levels. Patients with stage IIA colon cancer (N = 3477) diagnosed between 2010 and 2015 were identified using the Surveillance, Epidemiology, and End Results (SEER) database. Kaplan-Meier and Cox proportional hazards regression models were used to assess the prognostic effect of CEA on CSS and OS. Cox regression analysis demonstrated that CEA was an independent risk factor for CSS and OS in patients with stage IIA colon cancer (CSS: HR = 2.001, 95% CI 1.603-2.499, P < 0.001; OS: HR = 1.530, 95% CI 1.335-1.752, P < 0.001). In the subgroup with elevated CEA, patients received adjuvant chemotherapy had a better OS compared with those did not (χ2 = 10.585, p = 0.001). CEA was an independent risk factor for CSS and OS in patients with stage IIA colon cancer. Patients with stage IIA colon cancer with an elevated CEA level might benefit from adjuvant chemotherapy.

Oncotype DX testing does not affect clinical practice in stage IIa colon cancer.

Although studies have demonstrated the 12-gene Oncotype DX Colon Recurrence Score's (RS) validity in predicting recurrence and influence on physician-patient decision-making, its discriminatory power and inability to predict response to treatment make its clinical impact uncertain. We sought to evaluate the influence of RS in the decision to offer adjuvant chemotherapy after resection of stage IIa colon cancer. A review of patients with stage IIa colon cancer who obtained the RS at a tertiary academic medical center was conducted. The main study outcome was decision to start adjuvant chemotherapy. The association between RS and the decision to obtain adjuvant chemotherapy was evaluated utilizing the Wilcoxon rank-sum test and area under the receiver operating characteristic curve. 52 of 105 patients with stage IIa colon cancer underwent RS testing. Overall, seven of 52 patients (13%) received adjuvant chemotherapy. 34 (65%) patients obtained the RS test despite having multiple other recurrence risk factors. There were no significant associations between any patient/tumor characteristic and RS score (all p > 0.08) or starting adjuvant chemotherapy (all p > 0.15). On multivariable analysis, there was no significant effect of RS on the odds of undergoing chemotherapy (OR 1.07, 95% CI 0.98-1.19; p = 0.14). There was no clear association between RS and starting adjuvant chemotherapy (AUC 0.64, 95% CI 0.36-0.91; p = 0.25). RS was not associated with the decision to start adjuvant chemotherapy. Given its lack of association with clinical decision-making and inability to predict clinical outcome, our data suggest the RS should not be obtained in patients with stage IIa colon cancer.

Fungating Mass on the Abdominal Wall.

A 77-year-old woman was admitted to the hospital with anemia (hemoglobin, 5.2 g/dL [reference range, 12.0–15.5 g/dL]) and a rapidly growing abdominal wall mass. She had a history of stage IIA colon cancer (T3N0M0) that was treated 5 years prior with a partial colon resection and adjuvant chemotherapy.

Association of perioperative serum carcinoembryonic antigen level and recurrence in low-risk stage IIA colon cancer.

The purpose is to investigate prognosis according to serum CEA levels before and after surgery in patients with stage IIA colon cancer who do not show high-risk features. Among the patients diagnosed with colon adenocarcinoma between April 2011 and December 2017, 462 patients were confirmed as low-risk stage IIA after surgery and enrolled. The ROC curve was used to determine cut-off values of pre- and postoperative CEA. Patients were classified into three groups using these new cut-off values. All recurrence occurred in 52 of 463 patients (11.2%). However, recurrence in group H was 15.9%, which was slightly higher than the other two groups (P = 0.04). Group L and M showed 10.5% and 12.8% overall survival, group H was higher at 21.0% (P = 0.005). Recurrence was the only risk factor in group H was significantly higher in group L (HR 2.008, 95% CI, 1.123-3.589, P = 0.019). Mortality was similar to recurrence (HR 1.975, 95% CI 1.091-3.523, P = 0.044). Among patients with low-risk stage IIA colon cancer, recurrence and mortality rates were higher when perioperative serum CEA levels were above a certain level. Therefore, high CEA level should be considered a high-risk feature and adjuvant chemotherapy should be performed.

The role of inflammatory parameters in predicting disease recurrence in patients with stage IIA colon cancer with no high-risk features

ABSTRACT Objective We aimed to investigate the roles of inflammatory parameters, including neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR), lymphocyte/monocyte ratio (LMR), and C-reactive protein/albumin ratio (CAR), in predicting disease recurrence in patients with stage IIA (T3N0M0) high microsatellite instability and microsatellite-stable colon cancer who had no risk factors associated with relapse. Materials and methods We evaluated 155 patients with colon cancer followed in 3 hospitals in Turkey between February 2009 and March 2020. These patients had stage IIA disease and had no risk factors associated with relapse. None of the patients received adjuvant chemotherapy. NLR, PLR, LMR, and CAR parameters were retrospectively obtained from laboratory results at the time of diagnosis, and their associations with disease recurrence were assessed. Results Over a median follow-up period of 38 months (range: 4–98 months), 11 of the 155 patients experienced relapse or developed metastases. Multivariate Cox analyses revealed that NLRs of ≥3.12 (hazard ratio [HR]: 0.041, 95% confidence interval [CI]: 0.048–0.826, p = 0.006) and CARs of ≥0.027 (HR: 0.199, 95% CI: 0.004–0.404, p = 0.026) were independent prognostic markers predicting relapse. The median 5-year recurrence-free survival rate of patients with NLRs of ≥3.12 at the time of diagnosis was 88.0%; this rate was 100% in patients with NLRs of <3.12 (p < 0.001). Similarly, the median 5-year recurrence-free survival rate of patients with CARs of ≥0.027 at the time of diagnosis was 84.7%; this rate was 95.7% in patients with CARs of <0.027 (p = 0.016). Conclusion In this study, NLR and CAR were found to be independent prognostic markers predicting disease recurrence in patients with stage IIA colon cancer who did not receive adjuvant chemotherapy due to low clinical risk.

Preoperative prognostic nutritional index predicts risk of recurrence after curative resection for stage IIA colon cancer

BackgroundPreoperative nutritional and inflammatory indices have been reported to be associated with the prognosis of patients with malignancy. We evaluated clinicopathological factors, including nutritional and inflammatory indices, and recurrence prognosis in patients with stage IIA colon cancer (CC) who underwent curative surgery. MethodsThis retrospective study included 197 patients with stage IIA CC who had undergone curative resection. We evaluated the association between prognostic nutritional index (PNI), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) with clinicopathological factors and prognosis for recurrence. For the recurrence-free survival (RFS) analysis, receiver operating characteristic (ROC) curves were used to determine appropriate cutoff values for PNI, NLR, and PLR. ResultsUnivariate analyses showed that PNI<44.8 (P = 0.028) was significantly associated with worse RFS in patients with stage IIA CC patients. In the multivariate analyses, PNI<44.8 (hazard ratio [HR] 2.082; 95% confidence interval [CI] 1.005–4.317; P = 0.049) independently and significantly predicted RFS. ConclusionPNI is a useful marker for predicting recurrence prognosis in post-resection patients with stage IIA CC.

Prognostic Factor and Survival Benefit of Adjuvant Chemotherapy in Stage IIA Colon Cancer

Purpose There is no clear evidence of the benefit of adjuvant chemotherapy (AC) in stage IIA colon cancer. Therefore, we aimed to evaluate the prognostic factors and survival benefit of AC in this disease.Methods A retrospective data collection for patients who underwent radical surgery for colon cancer between January 2008 and December 2015 was undertaken. The cohort was divided into the no-AC and AC groups.Results We included 227 patients with stage IIA colon cancer in our study cohort, including 67 and 160 patients in the no-AC and AC groups, respectively. The number of retrieved lymph nodes and the presence of tumor complications as obstruction or perforation were independent risk factors for survival. In the no-AC group, there was a significant difference in survival according to the number of retrieved lymph nodes. In the AC group, there were significant differences in survival according to sidedness and preoperative carcinoembryonic antigen (CEA). There was no significant difference in survival between the no-AC and the AC groups.Conclusion The number of retrieved lymph nodes and the presence of tumor complications were prognostic factors for stage IIA colon cancer but lymphovascular and perineural invasion were not. Sidedness and preoperative CEA could be used as factors to predict the benefit of adjuvant chemotherapy. Currently, it is believed that there is no benefit of AC for stage IIA colon cancer. Further studies are needed to determine the survival benefit of adjuvant chemotherapy in stage IIA colon cancer.

Survival impact of adjuvant chemotherapy in patients with stage IIA colon cancer: Analysis of the National Cancer Database.

Utility of adjuvant chemotherapy for stage II cancer remains a matter of debate. Clinical guidelines suggest adjuvant chemotherapy for stage II tumors with high-risk features, in particular T4 tumors. However, limited consensus exists regarding the importance of other high-risk features (lymphovascular or perineural invasion, microsatellite instability). Our study aimed to investigate the impact of adjuvant chemotherapy for stage IIA (T3N0) colon cancer patients. Patients who underwent colectomy for stage IIA colon adenocarcinoma (2010-2015) were identified in the National Cancer Database (NCDB) and divided in two groups based on receipt of adjuvant chemotherapy vs observation. Inverse probability of treatment weighting (IPTW)-adjusted Kaplan-Meier and Cox proportional hazards regression analyses were performed to compare overall survival between the two groups. Subgroup analysis of patients with specific high-risk features LVI, PNI and MSI was performed. Among 46 688 surgical patients with stage IIA colon adenocarcinoma 5937 (12.7%) received adjuvant chemotherapy, while 40 751 (87.3%) were observed. Five-year IPTW-adjusted survival was higher in the adjuvant chemotherapy group (79.7% [95% CI 79.1, 80.2]) compared to the observation group (70.3% [95% CI 69.7, 70.9]). Patients with high-risk pathological features showed an estimated 5-year survival benefit of 11.3% (78.2% [95% CI 77.4, 79.1] vs 66.9% [95% CI 65.9, 67.8]) when treated with adjuvant chemotherapy. This NCDB analysis revealed a survival benefit for patients with stage IIA colon adenocarcinoma and high-risk features that were treated with adjuvant chemotherapy.

Indication for and Effect of Adjuvant Chemotherapy for Stage IIa (T3N0M0) Colon Cancer.

PurposeThe efficacy of adjuvant chemotherapy (AC) in stage IIa colon cancer is controversial. This study aimed to investigate the factors influencing survival in patients with stage IIa colon cancer, the role of AC, and the indications for AC utilization by surgical oncologists.MethodsBetween January 2004 and December 2010, 736 patients with stage IIa colon cancer underwent curative resection in 1 of 6 participating hospitals. Factors related to survival were identified and analyzed according to whether AC was administered or not. After high- and low-risk groups were identified, their respective results were analyzed.ResultsThe 5-year overall survival (OS) of stage IIa colon cancer was 90.3%. With the exception of poorly differentiated histology, indications for AC did not include typical high-risk factors. The indications for AC were significantly younger patients, higher body mass index (BMI), lower American Society of Anesthesiologists (ASA) physical status classification, and higher histologic grade. BMI, preoperative carcinoembryonic antigen, and harvested lymph node (LN) count were significant factors for disease-free survival, while BMI and ASA physical status classification were significant factors for OS in the chemotherapy group. In the high-risk group, AC was associated with increased OS in univariate analysis. BMI and harvested LN count were statistically significant in multivariate analysis.ConclusionSurgical oncologists consider the patient’s condition and postoperative course rather than high-risk factors to determine use of AC. Regardless of AC use, both the extent of surgery and the patient’s subsequent status affected the survival rate in the high-risk group. None of the factors identified influenced survival rate in the low-risk group.

P-117 - Stage IIa colon cancer: adjuvant chemotherapy in real life

P-117 - Stage IIa colon cancer: adjuvant chemotherapy in real life

Prognostic role of tumour-infiltrating T lymphocytes in stage IIA (T3N0) colon cancer: A broad methodological study in a fairly homogeneous population

AimTumour-infiltrating T lymphocytes (TIL) are considered to be a reliable prognostic marker in CC, but the use in daily practice is unclear. We investigated the survival effect of TIL methodologically in a highly homogeneous population. MethodsSeventy-two stage IIA (T3N0) CC patients who underwent surgical resection from 2000 to 2014 were included. CD3 and CD8 were separately scored for different blocks, areas and foci. To the best of our knowledge, this study has the most comprehensive methodology in the literature. ResultsForemost, we searched for the optimal evaluation method. We found better results with Model A (deepest invasive block&hot spot area&invasive margin focus), e.g. for CD3, the relationship with prognostic factors [Crohn’s-like reaction (p = 0.015), positive surgical margin (p = 0.019), Mismatch repair proteins deficiency (p = 0.003), advanced grade (p = 0.015)], the correlation of distinct estimates (r = 0.708), the reproducibility of research (Κappa = 0.60–0.71), and the usefulness of cut-off value (area of under ROC = 0.800 [0.683–0.917]) were best. Then, survival analysis was performed with two better methods including Model A. In univariate analysis, low TIL with Model A was associated with worse OS (CD3, p < 0.001; CD8, p = 0.023) and RFS (CD3, p < 0.001; CD8, p = 0.005). Multivariate analyses confirmed low TIL with same method as an independent worse prognostic marker for OS (CD3, Hazard ratio [HR] = 1.42 [1.10–1.85], p = 0.005) and RFS (CD3, HR = 1.46 [1.17–1.83], p = 0.001; CD8, HR = 1.32 [1.05–1.64], p = 0.032). ConclusionsOur results confirm that low TIL is an independent worse prognostic marker in stage IIA (T3N0) CC and that the use of CD3 with Model A can contribute to improving the prognostication of early CCs.

Colon Adenocarcinoma Stage IIA-Can We Predict Relapse?

To determine prognostic factors for stage IIA colon cancer (CC) recurrence in patients undergoing curative intent surgery without adjuvant treatment. Single-centre cohort study. All patients with stage IIA CC discussed in a multidisciplinary colorectal cancer clinic from January 2010 to December 2012 were evaluated. Clinical data, laboratory data and tumour features, including expression of DNA repair proteins (EDRP), were analysed. Assessment of overall and disease free survival, recurrence, recurrence site and recurrence's method of diagnosis was performed. The associations between variables were tested through the Fisher's exact test (SPSS 23). Fifty-five patients were included (55% male gender; mean age at diagnosis was 70.3years (42-88)). CC was in the left colon in 62%, high grade in 7% and had lymphovascular invasion in 7% of the cases. Only one patient was submitted to emergent surgery for obstructive symptoms. In 55% of cases ≥ 12 lymph nodes were collected. There was EDRP loss in nine patients (MLH1/PMS2: six; MSH2/MSH6: three)-only two fulfilled revised Bethesda criteria. Recurrence occurred in five patients (8.9%), and it was diagnosed through surveillance in all of them. No variable showed a statistically significant association with recurrence; however, there were no recurrences in patients with EPRD loss (p= 0.209). Mean follow-up time was 43months (2-70). In those with recurrence, mean disease-free survival was 23.4months. The overall good prognosis and absence of recurrence predictive factors were confirmed, validating the decision of not to submit stage IIA CC patients to chemotherapy risks.

Evaluating the Guiding Role of Elevated Pretreatment Serum Carcinoembryonic Antigen Levels for Adjuvant Chemotherapy in Stage IIA Colon Cancer: A Large Population-Based and Propensity Score-Matched Study.

Objective: This study was to investigate guiding role of elevated pretreatment serum carcinoembryonic antigen (CEA) levels for ACT receipt in stage IIA colon cancer.Methods: Eligible patients diagnosed with stage IIA colon cancer (N = 21848) were identified from the Surveillance, Epidemiology, and End Results (SEER) database between January 2004 and December 2010. Pearson's chi-squared tests, Cox proportional hazards regression models, and Kaplan-Meier methods were performed. Propensity score matching (PSM) was used to decrease the risk of biased estimates of treatment effect.Results: Multivariate Cox analysis indicated that, in CEA-elevated group, receiving or not receiving ACT did not presented statistically CSS difference [hazard ratio (HR) = 0.940, 95% confidence interval (CI) = 0.804–1.097, P = 0.431]; in CEA-normal group, receiving or not receiving ACT also did not presented statistically CSS difference (HR = 0.911, 95% CI = 0.779–1.064, P = 0.239). After PSM, Kaplan-Meier analyses showed that there was no statistical CSS difference between receiving or not receiving ACT (P = 0.64).Conclusion: ACT did not show substantial survival benefit in stage IIA colon cancer with elevated pretreatment serum CEA levels. Stage IIA disease with elevated pretreatment serum CEA should not be treated with ACT.

Survival benefit of adjuvant chemotherapy for patients with poorly differentiated stage IIA colon cancer.

Background: The effect of adjuvant chemotherapy on stage II colon cancer remains constantly controversial. Recently, however, several studies have reported the definite survival benefit of adjuvant chemotherapy (ACT) in T4 disease (stage IIB and IIC) among stage II colon cancer patients. The following study investigates the efficacy of ACT in patients with poorly differentiated stage IIA colon cancer.Methods: The first cohort of eligible patients (N=38384) diagnosed with stage IIA colon cancer was selected from the Surveillance, Epidemiology, and End Results database (SEER) between January 1, 2004, and December 31, 2010. Cox proportional hazards regression analyses and Kaplan-Meier curves were used to evaluate the survival benefit following ACT. Our findings were also evaluated in Fudan University Shanghai Cancer Center (FUSCC) cohort form FUSCC database.Results: In SEER cohort, poorly differentiated or undifferentiated tumor grade was associated with 21.5% increased cancer-specific mortality in patients who did not receive ACT (HR=1.215, 1.004-1.469, P=0.045, using poorly differentiated or undifferentiated ACT as a reference). In FUSCC cohort, poorly differentiated or undifferentiated tumor grade was also associated with increased DFS in patients who received ACT (HR = 0.160, 95% CI = 0.017-1.505, P=0.109, using poorly differentiated or undifferentiated, non-ACT as a reference). In addition, patients with poorly differentiated or undifferentiated tumor who did not receive ACT had a higher risk of distant metastasis and recurrence compared to patients who received ACT (log-rank P=0.027 and 0.119, respectively).Conclusion: ACT decreased the recurrence rate and distant metastasis rate thus improving prognosis for poorly differentiated or undifferentiated stage IIA colon cancer.

Abstract 3313: Epigenetic biomarkers of prognosis in stage IIA colon cancer

Abstract Adjuvant therapy is a systemic treatment administered after primary tumor resection to reduce the risk of relapse and death in colorectal cancer (CRC) patients. Generally, adjuvant treatment is recommended for stage III and ‘high-risk' stage II CRC (NCCN guidelines). Nonetheless, adjuvant treatment is still debated for stage IIA (T3N0) patients, whose estimated recurrence rate is 15-20% in the absence of any further therapy after resection of the primary tumor. With the aim to find additional prognostic biomarkers that could improve current patient selection, we analyzed the global methylation profile of a discovery group of 10 relapsing/non-relapsing stage IIA colon cancer samples, without any other known risk factor (low-risk), by Illumina Epic 850K array. We identified a panel of 25 Illumina probes that were able to predict recurrence in chemotherapy-naïve patients. Then, we assessed the methylation of the most predictive Cytosine-Guanine (CpG) dinucleotides in 107 stage IIA colon cancer patients from two different cohorts, by EpiTYPER technology. We validated several CpGs as differentially methylated in relapsing vs. non-relapsing CRCs (p&amp;lt;0.05). For these CpG sites, we analyzed the methylation level also in the matching normal mucosa surrounding the tumor, to identify potential premalignant epigenetic lesions. In addition, we examined the association between the methylation level at specific CpG sites and prognostic clinical characteristics, overall survival and time-to-relapse. We concluded that the analysis of epigenetic alterations in archival colon cancer tissues could increase the panel of risk factors predictive for recurrence, and thus improve the selection of patients who could benefit from adjuvant therapy. Citation Format: Sara Pagotto, Elisa Porcellini, Maria G. Bacalini, Diletta Sarti, Ingrid Garajova, Elisabetta Broseghini, Noemi Laprovitera, Francesco Vasuri, Paolo Garagnani, Renato Mariani-Costantini, Michele Basso, Rosa Visone, Luigi M. Larocca, Manuela Ferracin, Angelo Veronese. Epigenetic biomarkers of prognosis in stage IIA colon cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3313.

Macroscopic serosal invasion and small tumor size as independent prognostic factors in stage IIA colon cancer.

This study aimed to investigate the prognostic factors of patients with stage IIA (T3N0M0) colon cancer in terms of macroscopic serosal invasion and small tumor size. We enrolled 375 stage IIA colon cancer patients who underwent curative resection between January 2004 and December 2011. Macroscopic serosal invasion was defined as tumor nodules or colloid changes protruding the surface of the serosa. The clinicopathologic characteristics were analyzed to identify independent prognostic factors. The median follow-up was 47months (range, 1-90months). On multivariate survival analysis, macroscopic serosal invasion (adjusted hazard ratio [HR] = 4.750; p = 0.013), tumor size < 5cm (adjusted HR = 3.112, p = 0.009), perineural invasion (adjusted HR = 3.528; p = 0.002), < 12 retrieved lymph nodes (adjusted HR = 4.257; p = 0.002), and localized perforation (adjusted HR = 7.666; p = 0.008) were independent risk factors for recurrence. We found novel prognostic factors of stage IIA colon cancer, including macroscopic serosal invasion and small tumor size (< 5cm). Further studies are needed to evaluate the benefit of adjuvant chemotherapy in patients with these prognostic factors.