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The 2010 Patient Protection and Affordable Care Act mandated preventive screening coverage and provided support to participating states for Medicaid coverage. The association of Medicaid expansion with colon cancer stage at diagnosis is unknown.This study aimed to determine whether the proportion of patients diagnosed with early stage colon cancer changed over time within states that expanded Medicaid compared with nonexpansion states.This is a cross-sectional cohort study.This study evaluated multicenter registry data from the National Cancer Database (2006-2016).There were 25,462 uninsured or Medicaid-insured patients with newly diagnosed colon cancer who resided in 2014 Medicaid expansion or nonexpansion states.This study assessed the annual proportion of patients with early stage (I-II) versus late stage (III-IV) colon cancer.A total of 10,289 patients were identified in expansion states and 15,173 patients in nonexpansion states. Cohorts were similar in age (median 55 years) and sex (46.7% female). A greater proportion of patients in nonexpansion states were Black (33.4% vs 24.0%) and resided in a zip code with median income$38,000 (39.7% vs 28.2%) and lower educational status (37.4% vs 28.1%). In 2006, the proportions of patients with early stage colon cancer in expansion and nonexpansion cohorts were similar (33.2% vs 32.5%). The proportion of patients with early stage colon cancer within nonexpansion states declined by 0.8% per year after 2014, whereas the proportion within expansion states increased by 0.9% per year after 2014 ( p0.05). By 2016, the absolute difference in the propensity-adjusted proportion of early stage colon cancer was 8.8% (39.7% vs 30.9%, p0.001).National Cancer Database data are obtained only from Commission on Cancer-accredited sites and are not population based.After Medicaid expansion in 2014, the proportion of patients diagnosed and treated at Commission on Cancer-accredited facilities with early stage colon cancer increased within expansion states and decreased in nonexpansion states. Increase in insurance coverage may have facilitated earlier diagnosis among patients in expansion states. See Video Abstract at http://links.lww.com/DCR/B804 .ANTECEDENTES:La Ley del Cuidado de Salud a Bajo Precio del 2010 ordenó la cobertura de exámenes preventivos y brindó apoyo a los estados participantes para la cobertura de Medicaid. Se desconoce la asociación de la expansión de Medicaid con el estadio del cáncer de colon en el momento del diagnóstico.OBJETIVO:Determinar si la proporción de pacientes diagnosticados con cáncer de colon en estadio temprano cambió con el tiempo dentro de los estados que expandieron Medicaid en comparación con los estados sin expansión.DISEÑO:Estudio de cohorte transversal.ENTORNO CLINICO:Datos de registro multicéntrico de la Base de datos nacional de cáncer (2006-2016).PACIENTES:Había 25,462 pacientes sin seguro o asegurados por Medicaid con cáncer de colon recién diagnosticado. Exposición: Residencia en estados de expansión o no expansión de Medicaid en el 2014.PRINCIPALES MEDIDAS DE RESULTADO:Proporción anual de pacientes con cáncer de colon en estadio temprano (I-II) versus tardío (III-IV).RESULTADOS:Se identificaron un total de 10.289 pacientes en estados de expansión y 15.173 pacientes en estados de no expansión. Las cohortes fueron similares en edad (mediana de 55 años) y sexo (46,7% mujeres). Una mayor proporción de pacientes en estados sin expansión eran de raza negra (33,4% vs 24,0%) y residían en un código postal con ingresos medios$38 000 (39,7% vs 28,2%) y un nivel educativo más bajo (37,4% vs 28,1%). En el 2006, las proporciones de pacientes con cáncer de colon en estadio temprano en cohortes en expansión y sin expansión fueron similares (33,2% vs 32,5%). La proporción de pacientes con estadio temprano dentro de los estados sin expansión disminuyó en un 0,8% por año después del 2014, mientras que la proporción dentro de los estados de expansión aumentó en un 0,9% por año después del 2014 (p0,05). Para el 2016, la diferencia absoluta en la proporción ajustada por propensión de cáncer de colon en estadio temprano fue de 8.8% (39.7% vs 30.9%, p0.001).LIMITACIONES:Los datos de la Base de datos nacional de cáncer se obtienen únicamente de los sitios acreditados por la Comisión de cáncer y no se basan en la población.CONCLUSIONES:Después de la expansión de Medicaid en el 2014, la proporción de pacientes diagnosticados y tratados en instalaciones acreditadas por la Comisión de Cáncer en pacientes con cáncer de colon en estadio temprano aumentó dentro de los estados de expansión y disminuyó en los estados de no expansión. El aumento de la cobertura del seguro puede haber facilitado un diagnóstico más temprano entre los pacientes en estados de expansión. Consulte Video Resumen en http://links.lww.com/DCR/B804 . (Traducción- Dr. Francisco M. Abarca-Rendon ).

The aim of this study was to evaluate the potential impact of tumor size on the long-term outcome of colon cancer (CC) patients after curative surgery. A total of 782 curatively resected T4a stage CC patients without distant metastasis were enrolled. Patients were categorized into 2 groups according to the best threshold of tumor size: larger group (LG) and smaller group (SG). Propensity score matching was used to adjust for the differences in baseline characteristics. The ideal cutoff point of tumor size was 5 cm. In the multivariate analysis for the whole study series, tumor size was an independent prognostic factor. Patients in the LG had significant lower 5-year overall survival (OS) and relapse-free survival (RFS) rates (OS: 63.5% versus 75.2%, P P

Background: Colon cancer is the 3rd most common cancer in men and women combined, with an occurrence rate of 4.49% for men and 4.15% for women. The 2018 expectation is 50,630 deaths related to colon cancer in the United States (American Cancer Society Facts and Figures 2018). Early detection is increasing with nearly 45% of colon cancers diagnosed as stage I/II (Sarah Cannon Cancer Registry 2015). Treatment for early stage I/II colon cancer patients usually involves surgery then surveillance. On-site navigators perform their duties by patient need and barriers to care. Late stage III/IV colon cancer patients require more assistance and face more barriers, which often leaves early stage I/II patients without an advocate. This disparity can lead to lower rates of follow-up care for early stage I/II patients. Sarah Cannon created a program for virtual colon navigation (VCN) to determine if early stage I/II patients benefit from a virtual navigator who offers support by phone throughout their disease process. Objectives: The goal was to increase early stage I/II patients’ knowledge of their cancer and convey the importance of compliance with follow-up care, such as repeat colonoscopy as recommended by their physician and NCCN Guidelines. Methods: By developing software that utilizes artificial intelligence, Sarah Cannon created an automated process to identify colon cancer patients at the time of diagnosis. This technology then routes positive pathology reports to a VCN who contacts the early stage I/II patients by telephone, ensuring patient connection to the suitable physician for treatment. The VCN helps patients understand their diagnosis, provides education, assesses barriers to care, connects to resources, provides emotional support, and offers assistance with follow-up for physician visits, imaging and procedures such as colonoscopies, based upon NCCN Guidelines and physician guidelines. The VCN also connects stage III/IV patients with an on-site navigator in their region for more hands-on navigation. Results: Through September 2018, Sarah Cannon navigated 734 colon cancers, 332 stage I/II and 402 stage III/IV. With our increased capacity, Sarah Cannon/HCA maintained a 98% rate of follow-up care with new diagnoses of all stages of colon cancer. Conclusions: The VCN program allowed Sarah Cannon/HCA to improve care continuity and compliance based upon NCCN Guidelines for early stage I/II colon cancer patients throughout 5 regions and 37 facilities.

BackgroundTumor sidedness as a prognostic factor in advanced stage colon cancer (CC) is well established. The impact of tumor sidedness on the clinical outcomes of stage II and III CC has not been well studied.MethodsThe National Cancer Database (NCDB) was utilized to identify patients with pathological stage II and III primary adenocarcinoma of the colon from 2010 to 2015 using ICD-O-3 morphology and topography codes: 8140-47, 8210-11, 8220-21, 8260-63, 8480-81, 8490 and C18.0, 18.2,18.3, 18.5,18.6, 18.7. Univariate (UVA) and multivariable (MVA) survival analyses and Kaplan–Meier Curves with Log-rank test were utilized to compare overall survival (OS) based on tumor location and treatment received.ResultsA total of 35,071 patients with stage II (n = 17,629) and III (n = 17,442) CC were identified. 51.3% female; 81.5% Caucasian; median age 66 (range, 18–90). Majority of stage II and III tumors were right sided, 61.2% (n = 10,794) and 56.0% (n = 9,763). Microsatellite instability high (MSI-H) was more common in stage II compared to III, 23.3% (n = 4,115) vs 18.2% (n = 3,171) (p < 0.0001). In stage II MSI-H CC right was more common than left, 78.3% (n = 3223) vs 21.7% (n = 892). There was no significant difference in survival between stage II MSI-H left vs right (5-year OS 76.2 vs 74.7%, p = 0.1578). Stage II MSS CC right was more common than left, 56.0% (n = 7571) vs 44.0% (n = 5943), and survival was better in the left vs right (5-year OS 73.2 vs 70.8%, p = 0.0029). Stage III MSI-H CC was more common in the right than in the left, 75.6% (n = 2,397) vs 24.4% (n = 774) and survival was better in the left (5-year OS 62.5 vs 56.5%, p = 0.0026). Stage III MSS CC was more common in the right than in the left, 51.6% (n = 7,366) vs 48.4% (n = 6,905), and survival was better in the left vs right (5-year OS 67.0 vs 54.4%, p < 0.001).ConclusionSurvival was better in left sided tumors compared to right in stage II MSS, stage III MSS, and stage III MSI-H CC.

The aim of this study was to evaluate the potential impact of tumor size on the long-term outcome of CC patients after curative surgery. A total of 782 curatively resected T4 stage CC patients without distant metastasis were enrolled. Patients were categorized into 2 groups according to the best threshold of tumor size: larger group (LG) and smaller group (SG). Propensity score matching was used to adjust for the differences in baseline characteristics. The ideal cutoff points for tumor size was 5 cm. In the multivariate analysis for the whole study series, tumor size was an independent prognostic factors. Patients in the LG had a significant lower 5-year OS rate, but higher distant metastatic rate than those in the SG (37.1% versus 25.2%, P P

Background The objective of this study was to determine if there is an impact of surgical delay on 5-year overall survival (OS) from early stage colon cancer, and if so, to define how long surgery can safely be postponed. Methods Using the NCDB, we compared early (14–30 days) and delayed surgery (31–90 days) in patients with Stage I/II colon cancer. Outcomes included OS at five years and odds of death. Results Delayed resection conferred a decreased 5-year OS of 73.0% (95% CI, 72.6–73.4), compared to early resection 78.3% (95% CI, 77.9–78.8). When time to surgery was divided into one-week intervals, there was no difference in the odds of death with delay up to 35–41 days (6 weeks), but odds of death increased by 9% per week thereafter. Conclusions These data support that definitive resection for early stage colon cancer may be safely delayed up to 6 weeks., Highlights • It is unknown if resection can be safely delayed in patients with early stage colon cancer. • Retrospective analysis of 107,774 stage I/II colon cancer patients divided into early (14–30 days) versus delayed (31–90 days) cohorts. • Delayed resection conferred a decreased 5-year OS (73.0%) compared to early resection (78.3%). • Odds of death for each additional week of delay did not differ up to 6 weeks, but increased by 9% per week thereafter.

Colon cancer continues to be one of the leading causes of mortality and morbidity throughout the world despite the availability of reliable screening tools and effective therapies. The majority of patients with colon cancer are diagnosed at an early stage (stages I to III), which provides an opportunity for cure. The current treatment paradigm of early stage colon cancer consists of surgery followed by adjuvant chemotherapy in a select group of patients, which is directed at the eradication of minimal residual disease to achieve a cure. Surgery alone is curative for the vast majority of colon cancer patients. Currently, surgery and adjuvant chemotherapy can achieve long term survival in about two-thirds of colon cancer patients with nodal involvement. Adjuvant chemotherapy is recommended for all patients with stage III colon cancer, while the benefit in stage II patients is not unequivocally established despite several large clinical trials. Contemporary research in early stage colon cancer is focused on minimally invasive surgical techniques, strategies to limit treatment-related toxicities, precise patient selection for adjuvant therapy, utilization of molecular and clinicopathologic information to personalize therapy and exploration of new therapies exploiting the evolving knowledge of tumor biology. In this review, we will discuss the current standard treatment, evolving treatment paradigms, and the emerging biomarkers, that will likely help improve patient selection and personalization of therapy leading to superior outcomes.

About 75% of colorectal cancers are diagnosed as early stage, in which radical surgery is achievable. In the last decade, in Italy, the overall incidence of colorectal cancer has remained stable, while mortality gradually decreased, which is attributable to early diagnosis and improved medical, surgical and locoregional treatments. The Italian Medical Oncology Association formulated guidelines to manage early-stage colon cancer, including screening, diagnosis, treatment and follow-up, which we herein present.

The tumor-node-metastasis (TNM) classification, the presence of a mucinous component, and signet ring cells are well-known criteria for identifying patients at a high risk for recurrence and determining the therapeutic approach for early-stage colon cancer (eCC). Nevertheless, recurrence can unexpectedly occur in some eCC cases after surgical resection. The aims of the present study were to evaluate the relation of dysregulated MACC1, c-MET, and NM23-H1 expression with the histopathological features of tumors in recurrence formation in eCC cases. A total of 100 sporadic eCC patients without poor prognosis factors were evaluated in this study. The relationship between the altered expression of MACC1, c-MET, and NM23-H1 and pathological microenvironmental features, including the presence of tumor budding and desmoplasia, were assessed. The primary outcomes, including 5-year overall survival (OS) and disease-free survival (DFS), were also measured. Compared with nonrecurrent patients, the expression level of MACC1 was 8.27-fold higher, and NM23-H1 was 11.36-fold lower in patients with recurrence during the 5-year follow-up (p = 0.0345 and p = 0.0301, respectively). In addition, the coexistence of high MACC1 and low NM23-H1 expression and tumor budding was associated with short OS (p < 0.001). We suggest that the combination of reduced NM23-H1, induced MACC1, and the presence of tumor budding are promising biomarkers for the prediction of recurrence and may aid the stratification of patients with stage II colon cancer for adjuvant chemotherapy.

Introduction Circulating tumour (ct)DNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III CC treated with surgery +/- adjuvant chemotherapy. No study, however, has ever analysed the prognostic value of this biomarker in CC patients (pts) treated with neoadjuvant chemotherapy. We sought to evaluate the prognostic value of baseline and early, on-treatment changes of cfDNA and ctDNA in stage II-III CC pts who were treated with one cycle of neoadjuvant FOLFOX chemotherapy followed by surgery +/- adjuvant FOLFOX chemotherapy in the PePiTA trial. Methods PePITA was a multicentre, single-arm, prospective phase II trial aiming to test in vivo tumour chemosensitivity as assessd by metabolic response using 18F-FDG PET/CT scan of early stage CC and to evaluate its association with survival outcome (NCT00994864). Plasma samples were prospectively collected at baseline and 2 weeks (ie, after one cycle of neoadjuvant FOLFOX chemotherapy). cfDNA was isolated with the QIAmp circulating nucleic acid kit (Qiagen), and quantified with the Qubit fluorometer (Life-Technologies). cfDNA samples were bisulfite converted using the EZ DNA Methylation-Gold™ Kit (Zymo Research), with NPY and WIF1 being selected as universal methylation markers for ctDNA and analysed with digital droplet (dd)PCR technology. Data from ddPCR were processed with the QuantaSoft V1.6 software (BioRad). The primary outcome measure was 3-year disease-free survival (DFS). Receiver operating characteristics curve analyses, Kaplan-Meier method, cox proportional hazards models and log-rank tests were used. Statistical analyses were carried out with the SPSS for MacOS version 25.0 (SPSS Inc). Results 80 pts were included (ypStage I-II 56%, ypStage III 44%). After a median follow-up of 52.5 months, 3-year DFS was 80% (95%CI 71.2-90.8) and 5-year OS 84% (95%CI 75.2-94.9). Pts with high (≥1.2 ng/µl) baseline cfDNA level had worse 3-year DFS (48% vs 80%; HR 2.72, 95%CI 1.02-7.25; p=0.036) and 5-year OS (71% vs 90%; HR 5.36, 95%CI 1.14-25.28; p=0.017) than those with low baseline cfDNA level. In a multivariable analysis (including sex, ypStage and CEA), baseline cfDNA was the only factor showing a trend towards statistical significance (HR DFS 2.6, 95%CI 0.96-7.01; p=0.059; HR OS 4.65, 95%CI 0.97-22.32; p=0.055). Early changes of cfDNA (Δ ≥11%) after one cycle of neoadjuvant FOLFOX chemotherapy failed to predict survival (HR DFS 1.08, 95%CI 0.42-2.81; p=0.873; HR OS 0.68, 95%CI 0.19-2.39; p=0.543). ctDNA analyses are ongoing and will be presented at the meeting. Conclusions For the first time, we have shown that baseline cfDNA may predict survival outcome in early stage CC pts treated with neoadjuvant chemotherapy. Pending confirmation in larger series, testing for cfDNA at baseline could help select high-risk pts who may benefit from neoadjuvant, FOXTROT-like, treatment strategies. Citation Format: Giacomo Bregni, Elena Trevisi, Chiara Senti, Andrea Pretta, Caroline Vandeputte, Pashalina Kehagias, Elena Acedo Reina, Amélie Deleporte, Paraskevas Gkolfakis, Jean-Luc Van Laethem, Philippe Vergauwe, Marc Van den Eynde, Guido Deboever, Jos Janssens, Gauthier Demolin, Stephane Holbrechts, Marylene Clausse, Thierry De Grez, Marc Peeters, Lionel D'Hondt, Karen Geboes, Tatiana Besse-Hammer, Alexis Buggenhout, Françoise Rothé, Patrick Flamen, Alain Hendlisz, Francesco Sclafani. Prognostic value of baseline and early changes of circulating cell-free (cf)DNA in the neoadjuvant setting of early stage colon cancer (CC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 28.

3601 Background: A minimum of 12 lymph nodes are required during colectomy to accurately stage colon cancer. Prior studies in stage II colon cancer patients demonstrate association of inadequate lymph node examination (LNE) with worse overall survival (OS). No large-scale analogous studies related to LNE have been completed in stage I colon cancer patients. We evaluated patients with stage I colon cancer to determine the association between lymph node yield and OS. Methods: We reviewed the National Cancer Database between 2004-2015 to identify patients with pathologic stage I colon cancer (pT1N0 or pT2N0) who underwent definitive surgical resection. Patients who received radiation therapy or had missing values were excluded. Clinical and demographic characteristics were analyzed. Based on LNE, patients were stratified into 4 cohorts (LNE, 0-5, 6-11, 12-19, 20+) and 2 cohorts (0-11, 12+). Univariable and multivariable analyses were performed to identify variables associated with OS. Kaplan-Meier survival curves were computed to compare the cohorts. Results: We included 81,909 patients for analyses. Median age at diagnosis was 69. A majority were female (51.1%), white (83.8%), received care in a community cancer program (59.5%), and had a Charlson-Deyo score of 0 (66.6%). Only 0.7% of patients had a margin positive resection with a 2.5cm median tumor size. Patients were similarly split between pT1 and pT2. Suboptimal LNE was noted in 27.8% of patients. Patients with LNE were distributed - 10.7% (0-5), 17.1% (6-11), 43.4% (12-19) and 28.9% (20+). Postoperative 30-day mortality was 1.9%. 521 (0.7%) received systemic therapy. Ten-year survival in patients with 0-5 LNE was 52.8% compared to 60.1% with 20+ LNE. On multivariable analyses, patients aged ≥ 69, male sex, increasing tumor size (quartile), pT2 staging and a higher Charlson-Deyo score independently predicted worse OS (p < 0.001). LNE categories were significantly associated with OS (p < 0.001) (Table). On regrouping into 0-11 and 12+ LNE groups, 0-11 LNE group predicted worse OS (HR 1.22, p < 0.001). On multivariable analysis, the above variables continued to show similar association with OS (p < 0.001). Conclusions: Our study demonstrates that lymph node yield is associated with overall survival in patients with stage 1 colon cancer undergoing surgical resection. Furthermore, patients with suboptimal lymph node yield are associated with an inferior overall survival compared to those with optimal lymph node yield. Moreover, this study finds that a large number of patients ( > 25%) continue to have suboptimal lymph node yields. Future efforts should focus on improving the lymph node yield with optimal efforts by the surgeon and pathologist. Future studies should examine the role of systemic therapy in patients with inadequate lymph node yield.[Table: see text]

e15596 Background: Older patients with colorectal cancer are at increased risk of developing cardiovascular (CV) disease. 5-FU-based chemotherapy was found to increase CV morbidity; however, whether CV risks differ among different fluorouracil types, including infusional 5-FU, capecitabine, and tegafur-uracil (UFT), remains unclear. We aimed to assess the association between CV morbidities, including myocardial infarction and heart failure, and different 5-FU types in patients with colorectal cancer. Methods: We evaluated patients from Taiwan Cancer Registry linked with national health insurance research database with stage I to III colorectal cancer between January 1, 2004, and December 31, 2014. A multivariate Cox proportional model with age as the time scale was conducted for comparison. UFT alone was set as the control group. Results: In the cohort of 29176 patients (median [interquartile range] age, 65 [43-79] years), 2241 (7.6%) received UFT, 25181 (86.3%) received infusional 5-FU or capecitabine, 1754 (6%) received mixed. Overall, 290 patients were diagnosed with myocardial infarction (1.78 per 1000 person-years) during a median (interquartile range) follow-up of 5.5 years. Compared with those received UFT, those using infusional 5-FU or capecitabine showed no increased risk of myocardial infarction (weighted hazard ratio [HR], 0.84; 95% CI, 0.57-1.24). There were 376 patients diagnosed with heart failure, corresponding to 2.3 per 1000 person-years. The risks of heart failure between the UFT group and infusional 5-FU/capecitabine were similar (weighted HR, 0.9; 95% CI, 0.62-1.31). Conclusions: In this study, we did not observe any increased CV risk using infusional 5-FU or capecitabine compared with UFT alone use.

3600 Background: ctDNA is an indicator of minimal residual disease and negative prognostic factor in stage II-III CC treated with surgery +/- adjuvant chemotherapy (CT). No study, however, has ever analysed the prognostic value of this biomarker in CC patients (pts) treated with NACT. We sought to evaluate the prognostic value of baseline and early changes of cf/ctDNA in stage II-III CC pts who were treated with one cycle of NA FOLFOX CT followed by surgery +/- adjuvant FOLFOX CT in the PePiTA trial. Methods: PePiTA was a multicentre, single-arm, prospective phase II trial testing in vivo tumour chemosensitivity of early stage CC (as assessed by 18F-FDG PET/CT-based metabolic response to one cycle of NA FOLFOX) and its association with long-term outcome (NCT00994864). Plasma samples were prospectively collected at baseline, 2 weeks after one cycle of NA FOLFOX CT, and before surgery. NPY and WIF1 were selected as universal methylation markers for ctDNA and analysed with digital droplet (dd)PCR technology. Data from ddPCR were processed with the QuantaSoft v1.6 software (Bio-Rad). Survival outcome measures were 5-year disease-free survival (DFS) and 6-year overall survival (OS). ROC curve analyses, Kaplan-Meier method, cox proportional hazards models and log-rank tests were used. Statistical analyses were carried out with SPSS v25.0 (SPSS Inc.). Results: 80 pts were included (44 ypStage I-II and 36 ypStage III). After a median follow-up of 52.5 months, 5-year DFS and 6-year OS were 68% (95%CI 52-84) and 84% (95%CI 74-94), respectively. Pts with high (≥1600 ng/ml) baseline cfDNA had worse 6-year OS (HR 6.45, 95%CI 1.61-25.84; p = 0.008). Early changes of cfDNA after one cycle of NA FOLFOX CT failed to predict survival (HR DFS 0.96, 95%CI 0.38-2.43; p = 0.92; HR OS 0.62, 95%CI 0.16-2.50; p = 0.50). At baseline, 25 out of 60 (42%) ctDNA-assessable patients were positive. Detectable ctDNA at baseline (HR DFS 2.06, 95%CI 0.65-6.49; p = 0.22; HR OS 3.11, 95%CI 0.57-16.99; p = 0.19) or at any timepoint before surgery (HR DFS 1.65, 95%CI 0.54-5.04; p = 0.38; HR OS 2.80, 95%CI 0.54-14.44; p = 0.22) was not significantly associated with survival. A trend toward a significant association between ctDNA increase at surgery and 5-year DFS was found (HR 3.66, 95%CI 0.81-16.44; p = 0.09). Data on the correlation between early changes of cf/ctDNA and 18F-FDG PET/CT-based metabolic response will be presented at the meeting. Conclusions: For the first time, we have shown that baseline cfDNA may predict survival outcome in early stage CC pts treated with NACT. Pending confirmation in larger series, testing for cfDNA at baseline could help select high-risk pts who may benefit from FOxTROT-like, NACT treatment strategies. While analysis of ctDNA in this setting did not appear useful to predict prognosis, these results might be secondary to the small sample size.

Although liver metastasis commonly occurs in patients with colorectal cancer (CRC), it is infrequent that it presents several years after curative resection for early-stage disease. Even more unusual is development of intrabiliary growth type metastasis rather than parenchymal metastasis. When this occurs, it can be mistaken for cholangiocarcinoma. We present a case in a patient with history of pT1N0M0 CRC treated with sigmoidectomy 7 years previously who presented with abdominal pain and MRI revealing left hepatic ductal dilation with no accompanying mass. With a recent normal colonoscopy and carcinoembryonic antigen, he was diagnosed with cholangiocarcinoma. Anatomic hepatic resection was performed, and final pathology with immunohistochemistry revealed staining consistent with CRC metastasis rather than cholangiocarcinoma. Intrabiliary growth type metastasis is a rare occurrence, which leads to its misdiagnosis. Patients with an intrabiliary tumor and a history of CRC should have immunohistochemistry to confirm the diagnosis to ensure appropriate adjuvant treatment and counseling.

// Sohei Kobayashi 1 , Tyuji Hoshino 2 , Takaki Hiwasa 3 , Mamoru Satoh 4 , Bahityar Rahmutulla 1, 5 , Sachio Tsuchida 4 , Yuji Komukai 2 , Tomoaki Tanaka 1 , Hisahiro Matsubara 6 , Hideaki Shimada 7 , Fumio Nomura 4 , Kazuyuki Matsushita 1, 8 1 Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Chiba City, Chiba 260-8670, Japan 2 Department of Physical Chemistry, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba 260-8675, Japan 3 Department of Biochemistry and Genetics, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan 4 Divisions of Clinical Mass Spectrometry and Clinical Genetics, Chiba University Hospital, Chiba 260-8670, Japan 5 Department of Molecular Oncology, Graduate School of Medicine, Chiba University, Chiba City, Chiba 260-8670, Japan 6 Department of Academic Surgery, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan 7 Department of Gastroenterological Surgery, Toho University Omori Medical Center, Tokyo 143-8541, Japan 8 Department of Laboratory Medicine & Division of Clinical Genetics and Proteomics Chiba University Hospital, Chiba 260-8670, Japan Correspondence to: Kazuyuki Matsushita, email: kmatsu@faculty.chiba-u.jp Keywords: auto-antibodies, cancer biomarker, colorectal cancer, far-upstream element-binding protein-interacting repressor (FIR) = poly(U)-binding-splicing factor (PUF60) Received: June 29, 2016 Accepted: October 12, 2016 Published: October 15, 2016 ABSTRACT Anti-PUF60, poly(U)-binding-splicing factor, autoantibodies are reported to be detected in the sera of dermatomyositis and Sjogren’s syndrome that occasionally associated with malignancies. PUF60 is identical with far-upstream element-binding protein-interacting repressor (FIR) that is a transcriptional repressor of c-myc gene. In colorectal cancers, a splicing variant of FIR that lacks exon2 (FIRΔexon2) is overexpressed as a dominant negative form of FIR. In this study, to reveal the presence and the significance of anti-FIRs (FIR/FIRΔexon2) antibodies in cancers were explored in the sera of colorectal and other cancer patients. Anti-FIRs antibodies were surely detected in the preoperative sera of 28 colorectal cancer patients (32.2% of positive rates), and the detection rate was significantly higher than that in healthy control sera (Mann–Whitney U test, p < 0.01). The level of anti-FIRs antibodies significantly decreased after the operation ( p < 0.01). Anti-FIRs antibodies were detected in the sera of early-stage and/or recurrent colon cancer patients in which anti-p53 antibodies, CEA, and CA19-9 were not detected as well as in the sera of other cancer patients. Furthermore, the area under the curve of receiver operating characteristic for anti-FIRs antibodies was significantly larger (0.85) than that for anti-p53 antibodies or CA19-9. In conclusions, the combination of anti-FIRs antibodies with other clinically available tumor markers further improved the specificity and accuracy of cancer diagnosis.

251 Background: In 2010, the Affordable Care Act required insurance plans to cover preventative screening, and the Medicaid expansion provision enabled participating states to increase Medicaid coverage of uninsured individuals. The aim of this study was to determine whether the proportion of patients diagnosed with early vs. late stage colon cancer (CC) at Commission on Cancer (CoC) facilities differed over time within states that expanded Medicaid in January 2014 (MES) vs. non-Medicaid expansion states (NMES). Methods: A hospital-based cohort study of patients diagnosed with CC from 2006-2016 was performed using the National Cancer Database. Uninsured and Medicaid-insured patients in MES were compared with patients in NMES. Patients with Medicare, private, or government insurance were excluded. The observed proportions of patients with early (AJCC I-II) vs late (III-IV) stage within each cohort were compared over time. Propensity score adjusted probability of early stage at presentation was determined among patients residing in MES and NMES. Results: The study cohort included 10,289 patients in MES and 15,173 patients in NMES. Compared to MES, a greater proportion of patients in NMES were black (33.4% vs 24.0%), had a median income < $38,000 (39.7% vs 28.2%), and resided in a state with ≥21% of the population without a high school degree (37.4% vs 28.1%). The proportions of early stage CC in both cohorts in 2006 were similar. In NMES, this proportion remained constant over time until 2014 and declined by 0.8% per year after 2014. Within MES, the proportion of early stage CC increased by 0.6% per year until 2014 and 0.9% per year after 2014. By 2016, the absolute difference in the propensity adjusted proportion of early stage CC between cohorts was 8.8% (39.7% vs 30.9%, p < 0.001). Conclusions: Following Medicaid expansion in 2014, the proportion of patients presenting to a CoC facility with early stage CC increased over time within MES and declined in NMES. Further investigation, including population-based research, is warranted to determine if enrollment in Medicaid improves access to colorectal cancer screening and leads to earlier stage at diagnosis.

Purpose Clinically suspected T4 stage colon cancer from a preoperative exam is often diagnosed as T3 stage colon cancer pathologically after surgery, raising concerns about understaging. The aims of this study were to compare the survival of clinical T3 and T4 colon cancer patients who had received a pathologic T3 stage diagnosis postoperatively. Methods Patients who were diagnosed with pathologic T3 stage colon cancer postoperatively were reviewed. Patients with clinically suspected T3 or T4 stage cancer on preoperative exam were enrolled in the study. We compared patient demographics and survival of the cT3 and cT4 groups. Results Out of the 536 patients with pT3 colon cancer, 503 patients were cT3 (93.8%) and 33 patients were cT4 (6.2%) preoperatively. The most common reason for suspected clinical T4 stage cancer was free perforation (78.8%). There were no statistically significant differences between the 5-year overall survival and the total 5-year disease-free survival (DFS) between the cT3 and cT4 groups; however, local recurrence was significantly higher in the cT4 group (local 5-year DFS: 98.6% vs. 84.0%, P < 0.001). Multivariate analysis showed cT stage was associated with local recurrence, but the association was not statistically significant (P = 0.056). Conclusion Preoperative clinically suspected T4 stage colon cancer showed inferior local recurrence despite a postoperative pathologic diagnosis of T3 stage cancer. It is necessary to address the shortcomings of pathologic exams in the matter of the understaging of T4 colon cancer, and to reinforce the treatment for local control in patients with cT4 colon cancer.

The signal amplification methods of surface plasmon resonance (SPR) are mainly with sample selectivity. Herein proposed is a liquid core coupling SPR sensing method with adjustable sensitivity and universal applicability. A liquid core coupling unit and based on which a wavelength interrogation SPR sensor have been designed and constructed, in which a conventional chip could be used with an ingenious design and the sensitivity can be adjusted by changing the liquid core refractive index. The experimental data revealed that the sensitivity can be enhanced for 7.8 times by decreasing the liquid core refractive index from 1.5174 to 1.4502. The real applicability was validated by determination of carcinoembryonic antigen (CEA) with the signal intensity of the early stage colon cancer patient clearly up-regulated for nearly 18 folds compared with the healthy. It exhibited an adequate sensitivity, and further considering its simplicity avoiding the troublesome analysis process and/or chip preparing procedure, and extendibility to SPR imaging, the proposed method would be promising for medical diagnostics, food safety, environmental monitoring, and so on.

Evaluation of candidate surrogate endpoints using individual patient data from multiple clinical trials is considered the gold standard approach to validate surrogates at both patient and trial levels. However, this approach assumes the availability of patient-level data from a relatively large collection of similar trials, which may not be possible to achieve for a given disease application. One common solution to the problem of too few similar trials involves performing trial-level surrogacy analyses on trial sub-units (e.g., centers within trials), thereby artificially increasing the trial-level sample size for feasibility of the multi-trial analysis. To date, the practical impact of treating trial sub-units (centers) identically to trials in multi-trial surrogacy analyses remains unexplored, and conditions under which this ad hoc solution may in fact be reasonable have not been identified. We perform a simulation study to identify such conditions, and demonstrate practical implications using a multi-trial dataset of patients with early stage colon cancer.

Background Adjuvant! Online is a tool used for clinical decision making in patients with early stage colon cancer. As details of the tool's construction are not published, the ability of Adjuvant! Online to accurately predict outcomes for older patients (age 70 +) with node positive colon cancer receiving adjuvant chemotherapy is unclear. Methods Individual data from older patients with stage III colon cancer who enrolled into multiple trials within the ACCENT database were entered into the Adjuvant! Online program to obtain predicted probabilities of 5-year overall survival (OS) and recurrence-free survival (RFS). Median predictions were compared with known rates. As co-morbidities were not known for ACCENT patients, but required for calculator entry, patients were assumed to have either “minor” or “average for age” co-morbidities. Results 2967 older patients from 10 randomized studies were included. When “minor” co-morbidities were assumed, the median predicted 5-year OS rate of 64% nearly matched the actual rate of 65%; when “average for age” co-morbidities were assumed, the median prediction dropped to 58%, outside the CI for the actual rate. On the other hand, assuming “minor” co-morbidities gave a median 5-year RFS prediction of 62%, outside the 95% CI for the actual rate of 58%, while assuming “average for age” co-morbidities yielded a better median prediction of 57%. Conclusion Adjuvant! Online is reasonably accurate overall for predicting outcomes in older trial patients with stage III colon cancer, though accuracy may differ between 5-year RFS and 5-year OS predictions when a fixed degree of co-morbidities is assumed.

Colorectal cancer is one of the most common malignancies in the Westernized world. Particularly in the setting of metastatic disease, advances in the use of biomarkers have resulted in “personalized therapy” being an aspect of routine care. However, their role is less clear-cut in the context of adjuvant treatment for early-stage colon cancer. We still largely rely on conventional TNM staging to determine prognosis and treatment options in early-stage disease. Ongoing research is elucidating alternative measures, in the form of prognostic and predictive biomarkers, which may better assist in understanding the wide spectrum of outcomes in early-stage disease; as well as the potential to select and tailor appropriate therapeutic options for an individual rather than simply treating a disease and a “cancer stage”. This review outlines key discoveries and controversies in the application of biomarkers to tailor treatment in early-stage colon cancer.

3603Background: Sex is one of several factors known to affect drug efficacy and toxicity. Preliminary data in different types of cancers suggest a higher toxicity of chemotherapy in women. Aim of t...

3601Background: Initial dosing of adjuvant chemotherapy (ACT) is largely based on body surface area, but studies show that drug metabolism can vary significantly across patients. ACT-related toxici...

Advanced endoscopic technologies and techniques capable of providing localized resection of colonic primaries are entering clinical practice. As much as Natural Orifice Transluminal Endoscopic Surgery (N.O.T.E.S.) may ultimately provide for transmural resection with narrow margins, intraluminal techniques such as endoscopic submucosal resection can now effect excision of early stage tumors from within the colon. However, the limit on the application of these approaches is oncological providence as current staging requires en bloc mesenteric resection in every case to ensure that adequate nodal assessment is assured. Furthermore, this requirement is also a limiting factor on the advance of innovative procedures such as Single-Incision Laparoscopic Surgery and N.O.T.E.S.-hybrid techniques as these approaches, while likely adept at the definitive management of the primary, have limitations regarding their ability to provide full base mesenteric resection (due mostly to constraints on retraction capacity as well as operating field space and exposure). Therefore a means to accurately and efficiently identify those patients who are truly node negative (and so in whom radical mesenteric lymphadenectomy could be avoided) would allow all of these techniques to advance with a clear focus on address of the primary. This review analyses the current state of the art of regional staging in the colonic mesentery in place of formal lymphadenectomy. It includes deliberation of both preoperative non-invasive testing as well as novel means of employing N.O.T.E.S. approaches to allow direct determination of lymph node status (in particular that of sentinel nodes) by either rapid histopathological examination or by emerging technologies such as Optical Coherence Tomography that may provide optical or ‘virtual’ biopsy.

The requirement for nodal analysis currently confounds the oncological propriety of focused purely endoscopic resection for early-stage colon cancer and complicates the evolution of innovative alternatives such as natural orifice transluminal endoscopic surgery (NOTES) and its hybrids. Adjunctive sentinel node biopsy (SNB) deserves consideration as a means of addressing this shortfall.Data from two prospectively maintained databases established for multicentric studies of SNB in colon cancer that employed similar methodologies were pooled to establish technique potency selectively in T1/T2 disease (both overall and under optimized conditions) and to project potential clinical impact.Of 891 patients with T1-4, M0 intraperitoneal colon cancer, 225 had T1/T2 disease. Sentinel nodes were either not found or were falsely negative in 18 patients with T1/T2 cancers (8%) as compared with 17% (112/646) in those with T3/T4 disease (P = 0.001). Negative predictive value (NPV) in the former exceeded 95%, while sensitivity [including immunohistochemistry (IHC)] was 81%. In the 193 patients with T1/T2 disease recruited from those centers contributing22 patients, sensitivity was 89% and NPV 97%. Thus, in this cohort, SNB could have correctly prompted localized resection (obviating en bloc mesenteric dissection) in 75% (144) of patients, including 59 with T1 lesions potentially amenable to intraluminal resection alone as their definitive treatment. Forty-four patients (23.4%) would still have conventional resection, leaving three patients (1.6% overall) understaged (11% false-negative rate).These findings support the further investigation of SNB as oncological augment for localized resective techniques. Specific prospective study should pursue this goal.

Background Mismatch repair deficiency (dMMR) has been shown to confer a superior prognosis and is possibly predictive of a lack of benefit from fluoropyrimidine adjuvant chemotherapy (AC) for early-stage colon cancer (ESCC). We conducted a survey to assess medical oncologists' views regarding ESCC AC, with an emphasis on the use of MMR status to guide their recommendations. Materials and Methods The survey was distributed to all members of the Medical Oncology Group of Australia. Their demographic data, practice information, and views on the use of MMR status in ESCC and in 3 case scenarios were collected. The 3 case scenarios were a 68-year-old woman with moderate-risk stage II disease, who was eager to undergo AC (case 1); a 43-year-old woman with high-risk stage II disease, who was ambivalent regarding AC (case 2); and a 78-year-old woman with multiple comorbidities and high-risk stage II disease, who was eager to undergo AC. Results The survey response rate was 35% (190 of 550). Of the 190 responders, 152 (80%) routinely treated patients with colon cancer (CC) and completed the survey. For patients with stage II CC, 112 of 141 (79%) would use MMR status to assist AC recommendations, and 97 (69%) thought it changed their practice. In the case scenarios, 81% (case 1, 110 of 136), 67% (case 2, 92 of 137), and 43% (case 3, 57 of 133) used MMR status to assist AC recommendations. If dMMR was present, 78% (case 1, 86 of 110), 53% (case 2, 49 of 92), and 53% (case 3, 30 of 57) changed their initial recommendations by advising against AC. Conclusion The use of MMR status to assist AC recommendations for patients with stage II CC is an accepted practice for most Australian medical oncologists who responded to our survey.

Post-treatment survival experience of early colon cancer (CC) patients is well described in the literature, which states that cure is probable for some patients. However, comparisons of treated patients' survival versus that expected from a matched general population (MGP) are limited.A total of 32 745 patients from 25 randomized adjuvant trials conducted from 1977 to 2012 in 41 countries were pooled. Observed long-term survival of these patients was compared with expected survival matched on sex, age, country, and year, both overall and by stage (II and III), sex, treatment [surgery, 5-fluorouracil (5-FU), 5-FU + oxaliplatin], age (70 and 70+), enrollment year (pre/post 2000), and recurrence (yes/no). Comparisons were made at randomization and repeated conditional on survival to 1, 2, 3, and 5 years. CC and MGP equivalence was tested, and observed Kaplan-Meier survival rates compared with expected MGP rates 3 years out from each landmark. Analyses were also repeated in patients without recurrence.Within most cohorts, long-term survival of CC patients remained statistically worse than the MGP, though conditional survival generally improved over time. Among those surviving 5 years, stage II, oxaliplatin-treated, elderly, and recurrence-free patients achieved subsequent 3-year survival rates within 5% of the MGP, with recurrence-free patients achieving equivalence.Conditional on survival to 5 years, long-term survival of most CC patients on clinical trials remains modestly poorer than an MGP, but achieves MGP levels in some subgroups. These findings emphasize the need for access to quality care and improved treatment and follow-up strategies.

Background 18-Fluorodeoxyglucose positron emission tomography (PET) is used clinically to detect recurrent colon cancer after surgical resection, but the sensitivity of PET for premalignant colon lesions and early stage colon cancer is not well defined. Methods In a prospective study, 45 patients with a total of 58 colonic neoplasms, including premalignant polyps, premalignant, flat lesions, and early stage cancers, were evaluated by PET. Results The sensitivity of PET for cancer was 62% (8/13). PET detected 100% (7/7) of cancers 2 cm or larger but only 17% (1/6) of cancers smaller than 2 cm. PET detected 23% (3/13) of flat, premalignant lesions; 70% (7/10) of protruded, premalignant lesions 3 cm or larger; 38% (3/8) of protruded, premalignant lesions between 2 and 2.9 cm; and 14% (2/14) of protruded, premalignant lesions between 1 and 1.9 cm. There was no false-positive PET reading. Conclusions PET has limited sensitivity for flat, premalignant lesions; protruded, premalignant lesions smaller than 3 cm; and colon cancers smaller than 2 cm.

e15076 Background: With the advent of colon cancer screening, patients with early stage colon cancer will be more common in our clinics. The evidence supporting the absolute benefit of chemotherapy in resected Stage II and (to a lesser extent) Stage IIIA disease is poor. Not all patients benefit from chemotherapy and toxicity is a problem. There is a need for validated biomarkers to assess individual patient recurrence risk and discriminate absolute treatment benefit. Several studies have validated the role of the OncotypeDX testing in Stage II/IIIA disease. Our objective is to characterize whether this test impacted oncologists’ decisions in treating patients with Stage II/IIIA in the adjuvant setting. Methods: :The Onco typeDX assay is a multi-gene reverse-transcriptase-polymerase-chain-reaction test that analyses the expression of 12 genes involved in key biologic pathways in colon cancer. Stage II and Stage IIIA colon cancers were studied in affiliated hospitals of our region in southwest Ireland. All data collected is prospective and each colon cancer was assigned a recurrence risk score. Oncologists were blinded to this score and the decision to prescribe adjuvant chemotherapy was recorded. After un-blinding the score, a second decision was recorded and comparisons made. Results: :From August 2015 to September 2016, 70 patients have been recruited with M: F of 2:1. Median age at diagnosis was 65 years. Most patients (80%) had stage II disease, 11 of whom had mismatch repair loss on IHC. OncotypeDX testing has been carried out and reported for 59 patients (85%), MMR intact. Recurrence scores: < 30 in 46 patients (77.9%), 30-40 in 10 patients, and > 40 in 3 patients. The treatment plan was altered in 16 patients (27%), of whom 12 patients (20%) received none or less intense chemotherapy. Conclusions: We have shown that the decision to prescribe adjuvant chemotherapy was changed in 27% of patients. This test has helped to define patients with low scores, where chemotherapy-related toxicity is a concern especially in older patients. Absolute benefit of adjuvant chemotherapy versus the risk of toxicity should be discussed. . Hospital managers may be interested in cost savings due to a reduction in chemotherapy use.

e15148 Background: Recent data has suggested that disease biology and outcome of colon cancer may differ between right-sided and left-sided tumours. Here we explore differences in laterality based on disease characteristics and outcomes in a population-based cohort of early-stage colon cancer. Methods: Electronic records of treatment were linked to the Ontario Cancer Registry to identify all patients with colon cancer in 2002-2008. The study population included a 25% random sample of all patients with resected stage 0-III disease. Right-sided colon cancer was defined as any tumor arising in the cecum, ascending colon, hepatic flexure or transverse colon. Left-sided colon cancer was defined as any tumor arising from the splenic flexure, descending colon, sigmoid colon or rectosigmoid colon. Log binomial regression was used to identify factors associated with laterality. Cox models were used to explore the association between laterality and overall (OS) and cancer-specific (CSS) survival. Results: Among the study cohort (n = 6391) median age was 72 and 52% (3307/6391) had right-sided disease. Stage distribution was 2% (98/6391) stage 0, 17% (1091/6391) stage I, 38% (2446/6391) stage II, and 43% (2756/6391) stage III. Patients with right-sided colon cancer were more likely to be older (p < 0.001), female (p < 0.001) and have greater co-morbidity (p = 0.001). Right-sided cancer was more likely to be T4 (19% vs 16%, p = 0.001) and poorly differentiated (21% vs 10%, p < 0.001) but less likely to be node positive (42% vs 45%, p = 0.029) compared to left-sided disease. In adjusted analyses there was no difference in long-term survival for right-sided compared to left-sided colon cancer: OS HR 1.00 (95%CI, 0.92-1.08); CSS HR 1.00 (0.91-1.10). These results were consistent when the survival analyses were restricted to stage III disease: OS HR 1.03 (95%CI 0.93-1.14); CSS HR 1.10 (0.97-1.24). Conclusions: In this population-based cohort of early-stage resected colon cancer disease laterality was not associated with long-term survival.

Evaluation of surrogate endpoints using patient-level data from multiple trials is the gold standard, where multi-trial copula models are used to quantify both patient-level and trial-level surrogacy. While limited consideration has been given in the literature to copula choice (e.g., Clayton), no prior consideration has been given to direction of implementation (via survival versus distribution functions). We demonstrate that evenwith the “correct” copula family, directional misspecification leads to biased estimates of patient-level and trial-level surrogacy. We illustrate with a simulation study and a re-analysis of disease-free survival as a surrogate for overall survival in early stage colon cancer.

Information regarding the first and last authors is incorrectly omitted from the Competing interests statement. The Competing interests statement should read: "One of the authors (Dr. Juhl) is affiliated with Indivumed, GmbH. A provisional patent application has been filed by Georgetown University related to the technology described in this paper. Drs. Wellstein and Shivapurkar are named as inventors on this provisional patent application.This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials and does not provide a conflict of interest."

The increasing complexity of cancer chemotherapy makes it mandatory that pharmacists be familiar with these highly toxic agents. This column reviews various issues related to the preparation, dispensing, and administration of cancer chemotherapy, both commercially available and investigational.

BACKGROUND: The long-term natural history of early stage colon cancer and the outcome of long-term colonoscopic surveillance in routine specialist clinical practice after removal of the incident cancers have not been fully defined. In the present long-term evaluation up to 25 years, metachronous neoplasia, including both advanced adenomas and carcinomas, was defined.METHODS: All early stage colorectal cancer patients evaluated consecutively from a single clinical practice underwent follow-up colonoscopic evaluations after removal of the incident cancer and clearing of neoplastic disease. Colonoscopic surveillance was planned for two phases – initially on an annual basis for five years, followed by continued surveillance every three years up to 25 years with removal of any metachronous neoplastic lesion.RESULTS: A total of 128 patients (66 men and 62 women) with 129 incident early stage colorectal cancers were evaluated. Virtually all patients were symptomatic, usually with clinical evidence of blood loss. Incident early cancers were located throughout the colon, especially in the rectosigmoid, and showed no pathological evidence of nodal or other metastases. All patients evaluated during the first five years did not experience recurrent disease or have metachronous cancer detected. After five years, a total of 94 patients were evaluated up to 25 years; six of these patients were found to have seven metachronous colon cancers. All developed cancer more than seven years after removal of the incident colorectal cancer, including six asymptomatic adenocarcinomas, of which only one had evidence of single node involvement. Another patient in this cohort developed a poorly differentiated neuroendocrine carcinoma of the colon. In addition, 45% of patients had a total of 217 adenomas removed, including 11% of patients with 33 advanced adenomas. Among 14 patients with advanced adenomas, seven (50%) developed ≥1 late metachronous cancers.CONCLUSIONS: Following removal of an incident symptomatic early stage colorectal cancer, the risk of later metachronous neoplasia persists for an extended period more than five years after removal of the incident colorectal cancer. Moreover, risk for late metachronous cancer appears to be predicted by the presence of multiple adenomas or advanced adenomas; most metachronous cancers in this cohort were detected using colonoscopy before onset of symptoms and at an early stage.

Despite the generally excellent outcomes associated with early stage colon cancer treatment, a significant number of patients still develop recurrence and ultimately die from their disease. The standard tumor-node-metastasis (TNM) staging system cannot predict which patient will recur and will need additional therapy. This study aims to provide clinicians with a new computational tool based on quantitative analyses of histopathological images and a systems approach to accurately predict disease recurrence. We developed a set of advanced imaging algorithms including unsupervised dissection to automatically segment images into major histopathological components and to extract a broad spectrum of quantitative measurements from these components. Considering the complex interplay among various factors, a novel non-parametric random survival forest methodology was used to identify factors that most accurately predict the survival of colon cancer patients. Relative area and Haralick's contrast features of the tumor necrosis region have been identified as the most statistically significant predictors of survival for early stage colon cancer patients.

After diagnosis of colon cancer, the tumor is removed and the stage of the disease is provided by a pathologist. If the stage indicates relatively high risk of relapse, adjuvant chemotherapy is used for 6 or so months to reduce the probability of such relapse. This is a very common situation in oncology – used for many early stage colon cancer patients of whom there will be 143,000 in 2013 in US. This therapy is only partially effective since 52,000 patients will die of metastatic colon cancer in 2013. Despite being used for decades, there is much room for improvement.

e15148Background: MSI is detected in approximately 15% colorectal cancers, and associated with improved survival in early stage colon cancer. Heat shock protein 110 (HSP110) is a chaperone protein ...

The present study was designed to investigate the prognostic factors of stage IIA (pT3N0M0) colon cancer.We retrospectively reviewed consecutive patients with stage IIA colon cancer treated with curative surgery alone from January 2004 to June 2008 in Peking University Cancer Hospital. Patient demographics, and clinical, histopathologic, and laboratory data were analyzed. Univariate and multivariate analyses were carried out to identify prognostic factors associated with 3-year disease-free survival (DFS).For the 84 valid cases reviewed in this study, the 3-year DFS was 88.1 %. That for a group with elevated CEA was 77.1 % and for a group with a normal CEA level, it was 95.9 %, with statistical difference (p = 0.007). Multivariate analysis demonstrated that CEA level (p = 0.012, OR = 8.013, 1.573-40.817), expression of Ki67 (p = 0.099, OR = 3.298, 0.799-3.610), male gender (p = 0.024, OR = 7.212, 1.293-40.237), and anemia (p = 0.011, OR = 6.461, 1.537-27.151) were the independent prognostic factors for 3-year DFS. Stratified analysis revealed that an elevated CEA level combined with high expression of Ki67 was associated with poorer prognosis (3-year DFS 70 %).An elevated preoperative serum level of CEA and high expression of Ki67 in tumor tissue were predictors of poor prognosis for patients with stage IIA colon cancer. These patients should therefore be considered candidates for receiving intensive surveillance. Future clinical trials using multicenter patient cohorts should be prospectively performed to evaluate whether these high-risk patients could benefit from adjuvant chemotherapy to improve prognosis.

Estrogen receptor beta (ERβ) and TROP2 expressed in colon carcinoma and might play an important role there. We explored the relationship of ERβ and TROP2 expression with the prognosis of early-stage colon cancer. ERβ and TROP2 levels were assessed by immunohistochemistry in normal mucosa and tumoral tissues from 220 Chinese patients with T(3)N(0)M(0) (stage IIa) and T(4)N(0)M(0) (stage IIb) colon cancer in the Cancer Center, Sun Yat-sen University, who underwent curative surgical resection between 1995 and 2003. The Cox proportional hazards regression model was applied to analyze the overall survival (OS) data, and the ROC curve, Kaplan-Meier estimate, log rank test, and Jackknife method were used to show the effect of ERβ and TROP2 expression at different stages of cancer. The 5-year survival rates were not significantly different between the patients with stage IIa and stage IIb colon cancer (83 vs. 80 %, respectively). The high expression of ERβ was related to decreasing OS in stage IIa and stage IIb colon cancer, while the high expression of TROP2 was related to decreasing OS in stage IIb colon cancer. The expression of ERβ and TROP2 has tumor-suppressive and tumor-promoting effect in stage IIa and stage IIb colon cancer, respectively.

There are few clearly established prognostic factors available to guide the use of adjuvant chemotherapy in early stage colon cancer patients. Some of the most promising candidates include the invasion of extramural blood vessels by tumour cells and the densities of FOXP3+ T regulatory cells (Tregs) in tumour and adjacent normal colonic mucosal tissue. The aim of our study was to evaluate the prognostic significance of these markers in AJCC stage II colon cancer, with particular reference to lymphoid follicles in the mucosa. Histopathological review for the presence of vascular and serosal invasion was conducted on a series of 165 stage II colon cancers treated by surgery alone. Immunohistochemical staining for FOXP3 was performed on tumour tissue and histologically normal colonic mucosa from the surgical margin. Image analysis software was used to evaluate the density of FOXP3+ cells in the tumour core, invading margin and lymphoid follicles from the colonic mucosa. For survival analysis, cases were classified into high- or low-density of FOXP3+ cells according to the median value. The mean density of FOXP3+ Tregs in lymphoid follicles was twofold and fivefold higher than in the invading margin and tumour core, respectively. Multivariate analysis identified extramural vascular invasion (HR, 2.47; 95% CI: 1.00–6.07; P = 0.05) and high FOXP3+ cell density in lymphoid follicles (HR, 4.22; 95% CI: 1.49–11.91; P = 0.007) as independent factors for worse survival, whereas a high frequency of lymphoid follicles in histologically normal colonic mucosa was associated with better survival (HR, 0.31; 95% CI: 0.12–0.79; P = 0.014). Our data suggest that host factors related to the immune system have major prognostic significance in early stage colon cancer. The density of FOXP3+ cells within lymphoid follicles and the frequency of these structures in normal colonic mucosa represent novel and independent prognostic factors.