Localized Colon Cancer Research Articles

Hyperspectral imaging for colon cancer classification in surgical specimens: towards optical biopsy during image-guided surgery.

The main curative treatment for localized colon cancer is surgical resection. However when tumor residuals are left positive margins are found during the histological examinations and additional treatment is needed to inhibit recurrence. Hyperspectral imaging (HSI) can offer non-invasive surgical guidance with the potential of optimizing the surgical effectiveness. In this paper we investigate the capability of HSI for automated colon cancer detection in six ex-vivo specimens employing a spectral-spatial patch-based classification approach. The results demonstrate the feasibility in assessing the benign and malignant boundaries of the lesion with a sensitivity of 0.88 and specificity of 0.78. The results are compared with the state-of-the-art deep learning based approaches. The method with a new hybrid CNN outperforms the state-of the-art approaches (0.74 vs. 0.82 AUC). This study paves the way for further investigation towards improving surgical outcomes with HSI.

Analytical validation of the Immunoscore and its associated prognostic value in patients with colon cancer

BackgroundNew and fully validated tests need to be brought into clinical practice to improve the estimation of recurrence risk in patients with colon cancer. The aim of this study was...

Guidelines for time-to-event end-point definitions in adjuvant randomised trials for patients with localised colon cancer: Results of the DATECAN initiative

BackgroundThe variability of definitions for time-to-event (TTE) end-points impacts the conclusions of randomised clinical trials (RCTs). The Definition for the Assessment of Time-to-event Endpoints in CANcer (DATECAN) initiative aims to provide consensus definitions for TTE end-points used in RCTs. Here, we formulate guidelines for adjuvant colon cancer RCTs. MethodsWe performed a literature review to identify TTE end-points and events included in their definition in RCT publications. Then, a consensus was reached among a panel of international experts, using a formal modified Delphi method, with 2 rounds of questionnaires and an in-person meeting. ResultsTwenty-four experts scored 72 events involved in 6 TTE end-points. Consensus was reached for 24%, 57% and 100% events after the first round, second round and in-person meeting. For RCTs not using overall survival as their primary end-point, the experts recommend using disease-free survival (DFS) rather than recurrence-free survival (RFS) or time to recurrence (TTR) as the primary end-point. The consensus definition of DFS includes all causes of death, second primary colorectal cancers (CRCs), anastomotic relapse and metastatic relapse as an event, but not second primary non-CRCs. Events included in the RFS definition are the same as for DFS with the exception of second primary CRCs. The consensus definition of TTR includes anastomotic or metastatic relapse, death with evidence of recurrence and death from CC cause. ConclusionStandardised definitions of TTE end-points ensure the reproducibility of the end-points between RCTs and facilitate cross-trial comparisons. These definitions should be integrated in standard practice for the design, reporting and interpretation of adjuvant CC RCTs.

The impact of mismatch repair status to the preoperative staging of local colon cancer: Implications for clinical management.

16 Background: Computed tomography (CT) scan is standard in preoperative local staging of colon cancer. Tumours with a deficient mismatch repair (dMMR) system are characterised by unique clinical and pathophysiologic aspects that may impact on the accuracy of the preoperative CT staging. Methods: Data from the Danish Colorectal Cancer Group national clinical database addressing a cohort of patients operated for stage I-III colon cancer in 2010-15 was analysed. The analyses of MMR status had been conducted consecutively through means of immunohistochemistry. All CT scans were blindly assessed by a certified radiologist. Results: Data from 590 patients, operated at a specialised cancer centre were available for analyses. A dMMR phenotype was detected in 135 (22.9%) of the patients. The overall correlation of the clinical and pathological T-category was significant for both groups. There was inferior correlation between cN and pN (p > 0.05) in pMMR cancers with a higher degree of over-staging assessed by CT-scan, compared to a significant correlation between cN and pN stage in pMMR cancers (p < 0.01). Of the 91 dMMR tumours judged node-positive by the preoperative CT scan, 59 (64.8%) showed no sign of metastatic involvement at the postoperative assessment. Conclusions: The accuracy of preoperative CT lymph node staging in colon cancer seems to differ depending on MMR status and may impact the clinical management including the neoadjuvant setting.

Should calculation of chemotherapy dosage for bowel cancer be based on body composition?

Dosage of chemotherapy for colon cancer is currently based on the patient's body surface area. Several studies have identified an association between low fat-free mass and chemotherapy toxicity among patients with metastatic colorectal cancer. This has been less widely studied for localised disease. This review aims to summarise studies that have investigated the association between clinical signs of disease-related malnutrition (low body mass index, weight loss and low muscle mass) and tolerance of chemotherapy in patients with localised colon cancer. We conducted a systematic search in PubMed with various synonyms of the terms 'colorectal cancer', 'adjuvant chemotherapy', 'nutritional status' and 'toxicity'. The search was concluded in May 2019. Of 553 articles, 39 were considered relevant and read in full text. Ten of these fulfilled the inclusion criteria for this review. Nine of the ten studies indicate an association between clinical signs of disease-related malnutrition and dose-limiting toxicity. The association appears to be especially pronounced in patients with low fat-free mass. The results support the hypothesis that there is an association between disease-related malnutrition and the prevalence of toxicity and modification of the course of adjuvant chemotherapy in patients with localised colon cancer. The potential benefits of basing chemotherapy dosage on body composition in addition to body surface area should be investigated in clinical trials.

Detection of postoperative plasma circulating tumour DNA and lack of CDX2 expression as markers of recurrence in patients with localised colon cancer

BackgroundColon cancer (CC) is a heterogeneous disease. Novel prognostic factors beyond pathological staging are required to accurately identify patients at higher risk of relapse. Integrating these new biological factors, such as plasma circulating tumour DNA (ctDNA), CDX2 staining, inflammation-associated cytokines and transcriptomic consensus molecular subtypes (CMS) classification, into a multimodal approach may improve our accuracy in determining risk of recurrence.MethodsOne hundred and fifty patients consecutively diagnosed with localised CC were prospectively enrolled in our study. ctDNA was tracked to detect minimal residual disease by droplet digital PCR. CDX2 expression was analysed by immunostaining. Plasma levels of cytokines potentially involved in disease progression were measured using ELISAs. A 96 custom gene panel for nCounter assay was used to classify CC into colorectal cancer assigner and CMS.ResultsMost patients were classified into CMS4 (37%) and CMS2 (28%), followed by CMS1 (20%) and CMS3 (15%) groups. CDX2-negative tumours were enriched in CMS1 and CMS4 subtypes. In univariable analysis, prognosis was influenced by primary tumour location, stage, vascular and perineural invasion together with high interleukin-6 plasma levels at baseline, tumours belonging to CMS 1 vs CMS2 +CMS3, ctDNA presence in plasma and CDX2 loss. However, only positive ctDNA in plasma samples (HR 13.64; p=0.002) and lack of CDX2 expression (HR 23.12; p=0.001) were found to be independent prognostic factors for disease-free survival in the multivariable model.ConclusionsctDNA detection after surgery and lack of CDX2 expression identified patients at very high risk of recurrence in localised CC.

Reporting colon cancer staging using a template

PurposeThe purpose of this study was to evaluate the effect of completeness of the radiological reports in primary local staging colon cancer when using a template. MethodsThe study used primary staging reports retrieved from the departments RIS/PACS. Five key tumour descriptors were evaluated within each report: tumour morphology (polypoid or annular), information on tumour breach of the colon wall (≥ T3), tumour out-growth in mm, nodal status and TNM in conclusion. The failure to provide a description of the presence or absence of a feature in a report counted as ‘not reported’. To allow comparisons between reporting styles, the template or free-text style of reporting was also recorded. ResultsDuring a two year period, a total of 666 patients CT reports were evaluated at the colorectal center multidisciplinary team (MDT) conference. In 200 of these reports a template was used. Information on tumour morphology (polypoid or annular) was present in 81% of the template reports vs 9% in free-text style. The figures in percentage for information on tumour breach of the colon wall (≥ T3) were 93% vs 48 %, tumour out-growth in mm: 51% vs 17%, nodal status: 99% vs 86% and TNM in conclusion: 98% vs 51%. P < 0.0001. ConclusionThe present study provides additional support for the routine use of template reports to improve imaging reporting standards in colonic cancer.

Targeted next-generation sequencing of circulating-tumor DNA for tracking minimal residual disease in localized colon cancer.

A high percentage of patients diagnosed with localized colon cancer (CC) will relapse after curative treatment. Although pathological staging currently guides our treatment decisions, there are no biomarkers determining minimal residual disease (MRD) and patients are at risk of being undertreated or even overtreated with chemotherapy in this setting. Circulating-tumor DNA (ctDNA) can to be a useful tool to better detect risk of relapse. One hundred and fifty patients diagnosed with localized CC were prospectively enrolled in our study. Tumor tissue from those patients was sequenced by a custom-targeted next-generation sequencing (NGS) panel to characterize somatic mutations. A minimum variant allele frequency (VAF) of 5% was applied for variant filtering. Orthogonal droplet digital PCR (ddPCR) validation was carried out. We selected known variants with higher VAF to track ctDNA in the plasma samples by ddPCR. NGS found known pathological mutations in 132 (88%) primary tumors. ddPCR showed high concordance with NGS (r = 0.77) for VAF in primary tumors. Detection of ctDNA after surgery and in serial plasma samples during follow-up were associated with poorer disease-free survival (DFS) [hazard ratio (HR), 17.56; log-rank P = 0.0014 and HR, 11.33; log-rank P = 0.0001, respectively]. Tracking at least two variants in plasma increased the ability to identify MRD to 87.5%. ctDNA was the only significantly independent predictor of DFS in multivariable analysis. In patients treated with adjuvant chemotherapy, presence of ctDNA after therapy was associated with early relapse (HR 10.02; log-rank P < 0.0001). Detection of ctDNA at follow-up preceded radiological recurrence with a median lead time of 11.5 months. Plasma postoperative ctDNA detected MRD and identified patients at high risk of relapse in localized CC. Mutation tracking with more than one variant in serial plasma samples improved our accuracy in predicting MRD.

Use of Imaging During Staging and Surveillance of Localized Colon Cancer in a Large Insured Population.

Adherence to surveillance guidelines in resected colon cancer has significant implications for patient morbidity, cost of care, and healthcare utilization. This study measured the underuse and overuse of imaging for staging and surveillance in stage I-II colon cancer. The OptumLabs database was queried for administrative claims data on adult patients with stage I-II colon cancer who underwent surgery alone in 2008 through 2016. Use of PET and CT imaging was evaluated during both initial staging (n=6,921) and surveillance for patients with at least 1 year of follow-up (n=5,466). "High use" was defined as >2 CT abdominal/pelvic (CT A/P) or PET scans per year during surveillance. Overall, 27% of patients with stage I-II colon cancer did not have a staging CT A/P or PET scan and 95% did not have a CT chest scan. However, rates of staging CT A/P and CT chest scans increased from 62.0% (2008) to 74.8% (2016) and from 2.3% (2008) to 7.1% (2016), respectively. Staging PET use was overall very low (5.2%). During surveillance, approximately 30% of patients received a CT A/P or PET and 5% received a CT chest scan within the first year after surgery. Of patients who had surveillance CT A/P or PET scans, the proportion receiving >2 scans within the first year (high use) declined from 32.4% (2008) to 9.6% (2016) (P = .01). Although PET use remains appropriately low, many patients with stage I-II colon cancer do not receive appropriate staging and surveillance CT chest scans. Among those who do receive these scans during surveillance, high use has declined significantly over time.

The microRNA-200 family acts as an oncogene in colorectal cancer by inhibiting the tumor suppressor RASSF2.

This study aimed to determine whether manipulation of the microRNA-200 (miR-200) family could influence colon adenocarcinoma cell behavior. The miR-200 family has a significant role in tumor suppression and functions as an oncogene. In vitro studies on gain and loss of function with small interfering RNA demonstrated that the miR-200 family could regulate RASSF2 expression. Knockdown of the miR-200 family in the HT-29 colon cancer cell line increased KRAS expression but decreased signaling in the MAPK/ERK signaling pathway through reduced ERK phosphorylation. Increased expression of the miR-200 family in the CCD-841 colon epithelium cell line increased KRAS expression and led to increased signaling in the MAPK/ERK signaling pathway but increased ERK phosphorylation. Functionally, knockdown of the miR-200 family led to decreased cell proliferation in the HT-29 cells; therefore, increased miR-200 family expression could increase cell proliferation in the CCD-841 cell line. The present study included a large paired miR array dataset (n=632), in which the miR-200 family was significantly found to be increased in colon cancer when compared with normal adjacent colon epithelium. In a miR-seq dataset (n=199), the study found that miR-200 family expression was increased in localized colon cancer compared with metastatic disease. Decreased expression was associated with poorer overall survival. The miR-200 family directly targeted RASSF2 and was inversely correlated with RASSF2 expression (n=199, all P<0.001). Despite the well-defined role of the miR-200 family in tumor suppression, the present findings demonstrated a novel function of the miR-200 family in tumor proliferation.

Utilization of surgery and its impact on survival in elderly patients with localized colon cancer in the United States.

e15179 Background: For patients with localized colon cancer, surgical resection is the only curative treatment modality. Old age may be an independent factor associated with decreased receipt of surgery. We conducted this study to evaluate the utilization of surgery and its impact on survival in older patients with colon cancer in the United States. Methods: Surveillance, Epidemiology and End Results Database (SEER-18) was utilized to identify elderly patients (≥65 years) diagnosed from 2004-2013 with non-metastatic colon cancer (stage≤ III). Study population was divided into various cohorts based on race (Caucasian, African Americans, others), sex and age (&lt; 80 years and ≥80 years), histology grade, tumor side, and stage. Multivariate logistic regression model was utilized to assess factors associated with receipt of surgery. Kaplan-Meier estimators with the log rank test was used to compare median overall survival (Md OS) between the surgery arm and non-surgery arm. Statistical significance was defined for p &lt; 0.05. Results: Database identified 89,467 patients (54.7% female, 82.7% Caucasian; Median age 77 years). 94.6% (n = 84,656) of patients received surgery. On multivariate-analysis, left sided disease, lower grade tumor, lower stage, female gender, residents of lower median household income county, African Americans and age ≥80 years were less likely to receive surgery. The Md OS in the surgery arm was 87 months vs 69 months for non-surgery arm, p &lt; 0.001. This benefit was seen in all the three stages (stage I: Md OS 104 vs 75 months; stage II: Md OS 88 vs 50 months; stage III: Md OS 74 vs 37 months, p &lt; 0.001 for all comparisons). Additional analysis for octogenarians (age≥ 80 years) showed Md OS of 68 months in the surgery arm vs 48 months in the non-surgery arm, p &lt; 0.001). Conclusions: Our study showed significant utilization of surgery (94.6%) in elderly patients with localized colon cancer. There is a clear survival benefit to surgery even in patients with age≥ 80 years. Surgical resection with curative intent should be strongly considered in patients with good performance status irrespective of age.

Combination of tissues analysis and immune infiltrate in localized colon cancer using artificial intelligence in PETACC8 study.

3574 Background: We used artificial intelligence to perform tissue classification and count CD3 and CD8 in each subclass and determined their role in outcome prediction in PETACC8 cohort of stage III colon cancer treated with FOLFOX or FOLFOX plus cetuximab. Methods: We developed artificial intelligence aimed to detect tumor, healthy mucosa, stroma and immune cells on whole slide of CD3 and CD8 staining. The invasive margin (IM) was also automatically determined. Using a lasso algorithm, the software was able to detect digital parameters within the tumor core (TC) which were related to patients’ outcome (variable called DGMate for DiGital tuMor pArameTErs). CD3 and CD8 lymphocytes density were also quantified automatically by the software in TC and at IM. Associations with disease-free survival (DFS) were evaluated by multivariable Cox regression adjusting for age, T/N stage, sidedness, KRAS/BRAF, DNA mismatch repair (MMR). Results: On 1220 samples collected, data could be generated for 1018 patients. We observed that a high IM stromal area and a high DGMate were associated with a poorer DFS [HR 5.65 (95% CI, 2.34, 13.67), p &lt; 0.0001; HR 2.72 (95% IC, 1.92, 3.85), p&lt;0.001 respectively for the continuous variable]. A higher density of CD3+ TC, CD3+ IM and CD8+ TC were significantly associated with a longer DFS (HR 0.75 (95% IC, .66, .87), p&lt;0.0001; HR 0.78 (95% IC, .68, .88), p&lt;0.0001; HR 0.83 (95% IC, .71, .96), p=0.01). All these immune variables were significantly correlated with each other. ANOVA test demonstrated that CD3+ TC gave a similar prognostic value compared to the classical CD3/CD8 immunoscore (p=0.44). The combination of IM stromal area, DGMate and CD3 outperformed the classical CD3/CD8 immunoscore to estimate patients’ prognosis (C-index= 0.601 vs 0.578, p-value=0.04). Adding this new variable to classical clinical prognostic parameters we generated a nomogram which predicted the risk of relapse of stage III colon cancer with a stronger predictive value compared to clinical parameters or the immunoscore. Conclusions: We propose a new fully automated method of whole slide analysis using a software based on artificial intelligence which classify tissue and determine tumor and immune parameters on one single slide stained with CD3 antibody. This valuable strategy outperforms immunoscore and clinical outcome prediction models.

Surgery versus surgery with adjuvant radiotherapy for T4 colon cancer.

673 Background: There is no randomized prospective evidence to clarify the role of adjuvant radiotherapy in localized colon cancer. Despite this, national consensus guidelines recommend that adjuvant radiotherapy be considered for patients with T4 disease. Given the lack of prospective data, the aim of this study was to evaluate the role of adjuvant radiation therapy (RT) in colon cancer using two large national databases to help to guide treatment decisions. Methods: We evaluated the association of receipt of adjuvant RT with overall survival (OS), using the National Cancer Database (NCDB) and Surveillance, Epidemiology, and End Results Program (SEER), as well as with disease-specific survival (DSS) using SEER. We analyzed cohorts of patients with histologically confirmed locally advanced T4 adenocarcinoma of the colon, who underwent oncologic surgery with or without adjuvant radiation and had at least 5 years of follow up. For the NCDB cohort, we restricted RT patients to those who received a dose of 45-60 Gy and those who received treatment within 3 months after surgery. We used nearest-neighbor propensity score matching on the basis of age, race, sex, year of diagnosis, grade, N-stage, receipt of chemotherapy, anatomical subsite, margin status, and comorbidity score. To validate our findings, using SEER, we used propensity matching using the same covariates (except comorbidity). Results: After matching of the NCDB cohort, cox regression showed no statistically significant association of adjuvant radiotherapy with OS (HR=1.08; 95% CI 0.89 - 1.30; p=0.448). Using SEER, cox regression showed no statistically significant association of adjuvant radiotherapy with OS (HR=0.9; 95% CI 0.50 - 1.63; p=0.731) or DSS (HR=0.84; 0.54 – 1.33; p=0.46). Conclusions: In summary, after comprehensively adjusting for covariates using two independent national databases, we found no statistically significant association of adjuvant RT with overall- or disease-specific survival for T4 colon cancer. These findings are limited by the retrospective nature of the data and should be tested in a prospective fashion.

Low miR200c expression in tumor budding of invasive front predicts worse survival in patients with localized colon cancer and is related to PD-L1 overexpression

At the histological level, tumor budding in colon cancer is the result of cells undergoing at least partial epithelial-to-mesenchymal transition. The microRNA 200 family is an important epigenetic driver of this process, mainly by downregulating zinc-finger E-box binding homeobox (ZEB) and transforming growth factor beta (TGF-β) expression. We retrospectively explored the expression of the miR200 family, and ZEB1 and ZEB2, and their relationship with immune resistance mediated through PD-L1 overexpression. For this purpose, we analyzed a series of 125 colon cancer cases and took samples from two different tumor sites: the area of tumor budding at the invasive front and from the tumor center. We found significant ZEB overexpression and a reduction in miR200 in budding areas, a profile compatible with epithelial-to-mesenchymal transition. In multivariate analysis of the cases with localized disease, low miR200c expression in budding areas, but not at the tumor center, was an adverse tumor-specific survival factor (hazard ratio: 0.12; 95% confidence interval: 0.03–0.81; p = 0.02) independent of the clinical stage of the disease. PD-L1 was significantly overexpressed in the budding areas and its levels correlated with a mesenchymal transition profile. These results highlight the importance of including budding areas among the samples used for biomarker evaluation and provides relevant data on the influence of mesenchymal transition in the immune resistance mediated by PD-L1 overexpression.

Sporadic synchronous triple primary cancers in elderly female: Microsatellite instability high resectable colon cancer, epidermal growth factor receptor-mutated metastatic lung cancer, and neuroendocrine tumor of appendix

Colorectal cancer and lung cancer are the most common malignancies in the world. However, not all pulmonary nodules in a case of colon cancer are considered as metastasis, especially with features suggestive of limited colon disease without any nodal or liver involvement. The morphology of the pulmonary nodules is also an important consideration before subjecting the patient to another invasive procedure, as solitary pulmonary nodule with irregular margins, suggestive of another primary lesion. We describe a case of a patient with colon cancer, nonsmall cell lung cancer with single bone lesion, and neuroendocrine tumor of appendix. Initially suspected to be a case of metastatic colon cancer, the patient was later diagnosed as epidermal growth factor receptor-mutant metastatic pulmonary adenocarcinoma, with localized microsatellite instability high phenotype colon cancer.

Long-term oncological outcomes following emergency resection of colon cancer.

The relationship between emergency colon cancer resection and long-term oncological outcomes is not well understood. Our objective was to characterize the impact of emergency resection for colon cancer on disease-free and overall patient survival. Data on patients undergoing resection for colon cancer from 2006 to 2015 were collected from a prospectively maintained clinical and administrative database. The median follow-up time was 4.4years. Cox proportional hazards models were used to estimate the hazard ratios for recurrence and death for patients treated with surgery for an emergent presentation. Differences in initiation of, and timeliness of, adjuvant chemotherapy between emergently and electively treated patients were also examined. Of the 1180 patients who underwent resection for stages I, II, or III colon cancer, 158 (13%) had emergent surgery. After adjustment for patient, tumor, and treatment characteristics, the HR for recurrence was 1.64 (95% CI 1.12-2.40) and for death was 1.47 (95% CI 1.10-1.97). After adjustment for tumor characteristics, patients who underwent emergency resection were similarly likely to receive adjuvant chemotherapy (OR 1.1; 95% CI 0.70-1.76). The time from surgery to initiation of adjuvant chemotherapy was also similar between the groups. Emergency surgery for localized or regional colon cancer is associated with a greater risk of recurrence and death. This association does not appear to be due to differences in adjuvant treatment. A focus on screening and colon cancer awareness in order to reduce emergency presentations is warranted.

The prognostic value of signet ring cell histology in stage I/II colon cancer-a population-based, propensity score-matched analysis.

Previous research associated signet ring cell histology in colon cancer patients with poor survival outcomes. The aim of this study was to analyze the prognostic significance of signet ring cell histology on overall and cancer-specific survival in patients with localized colon cancer. Stage I and II colon cancer patients treated with surgical resection between 2004 and 2015 were identified in the Surveillance, Epidemiology, and End Results (SEER) database. Overall survival (OS) and cancer-specific survival (CSS) were assessed using risk-adjusted Cox proportional hazards regression models and propensity score methods. Eighty-eight thousand nine hundred fifty-eight stage I-II colon cancer patients were identified. Overall, 446 (0.5%) showed signet ring cell histology. In unadjusted analyses, the 5-year OS and CSS rates of patients with signet ring cell histology were 65.8 and 83.1%, respectively, compared with 74.3 and 88.7% in patients with non-signet ring cell adenocarcinoma (p values: OS, p < 0.001; CSS, p < 0.001). Neither in risk-adjusted Cox proportional hazard regression analysis (OS: hazard ratio (HR), 0.96 (95% CI, 0.82-1.12%) p = 0.616; CSS: HR, 1.01 (95% CI, 0.79-1.28%) p = 0.946) nor with propensity score matching (OS: HR, 0.96 (95% CI, 0.82-1.14%) p = 0.669 and CSS: HR: 1.09 (95% CI: 0.84-1.40%) p = 0.529), a survival disadvantage was found for signet ring cell histology. This is the first propensity score-adjusted population-based investigation on exclusively stage I and II colon cancer patients providing compelling evidence that signet ring cell histology does not negatively impact survival in stage I and II colon cancer after risk-adjusting for known prognostic factors. Therefore, standard treatment strategies can be applied in these patients.

Colorectal Cancer: Why Does Side Matter?

Colorectal cancer (CRC) is a heterogeneous disease, and the search for clinical and molecular prognostic and predictive factors is thus necessary to better tailor each individual patient's management. Primary tumor location (PTL) seems to act as a master prognostic factor pooling different clinical, pathological, and molecular poor prognostic factors. In fact, right-sided (RS) CRC patients are more frequently femaleand elderly with microsatellite unstable, BRAF mutated, CpG island methylator phenotype (CIMP)-high, poorly differentiated tumors, compared to left-sided (LS) CRC patients. PTL does not seem to clearly influence disease-free survival (DFS) in localised colon cancer even though the opposite prognostic value of RS tumors on DFS depending on RAS/BRAF mutational status has been recently suggested in these patients. In metastatic CRC (mCRC), the poor prognosis associated with RS tumors is confirmed in the most recent publications in the era of double and triple chemotherapeutic regimens and targeted agents. Concerning the predictive value of PTL, in patients with RAS wild-type mCRC in the first-line setting, anti-epidermal growth factor receptor (EGFR) therapy combined with chemotherapy appears to be more effective than bevacizumab in LS CRC, while patients with RS CRC benefit less from anti-EGFR therapy, and intensive chemotherapy plus bevacizumab may be more appropriate but EGFR antibodies remain an option if objective response is needed. Due to the limitation of the current data (unplanned and retrospective analyses), these conclusions must be interpreted with caution. Clinical trials in RS CRC may be of interest to clarify what is the best treatment strategy in these patients.

Utilization of imaging during staging and surveillance of localized colon cancer in a large insured population.

6616Background: It is unknown if staging and surveillance imaging in Stage I/II colon cancer are under- or over-utilized. On one hand, the Choosing Wisely campaign advocates against positron-emissi...

Optimizing Adjuvant Therapy for Localized Colon Cancer and Treatment Selection in Advanced Colorectal Cancer.

Results from the pivotal IDEA trial, which evaluated 3 versus 6 months of adjuvant oxaliplatin-based chemotherapy, are incorporated into the NCCN Guidelines for Colon Cancer. The guidelines recommend that for patients with low-risk stage III disease, the preferred regimen is CAPEOX for 3 months or FOLFOX for 3 to 6 months. For patients with high-risk stage III disease, the preferred regimen is CAPEOX for 3 to 6 months or FOLFOX for 6 months. In metastatic disease, tumor sidedness should be a consideration when choosing a biologic. For BRAF-mutated disease, several triplets are now recommended options. Importantly, for a subset of patients with metastatic disease, new to the NCCN Guidelines is the incorporation of nivolumab and pembrolizumab as subsequent therapy for those with microsatellite instability-high or mismatch repair-deficient tumors.