Classification of early-stage colon cancer with Immunoscore®: clinical evidence and case studies

Immunoscore® is a digital pathology diagnostic immunoassay used to complement tumor node metastasis staging for the prediction of recurrence risk in patients with early-stage colon cancer. In combination with standard clinicopathological features, Immunoscore® informs adjuvant chemotherapy decision-making for patients with early-stage colon cancer. Immunoscore® has been validated in patients with stage II/III colon cancer and demonstrated to be a stronger prognostic factor for survival than tumor node metastasis staging alone. Immunoscore® improves the prognostic definition of patients with colon cancer, the identification of those patients at high risk of tumor recurrence, and the ability to predict which patients will derive most benefit from the use of adjuvant chemotherapy. Immunoscore® has robust analytical performance characteristics which include good interlaboratory reproducibility and overall assay precision.

Complex Chromosome-Positive Acute Myelogenous Leukemia Identified 16 Months following the Completion of Capecitabine Chemotherapy for Early-Stage Colon Cancer

Capecitabine is an oral chemotherapy that is used to treat several cancer types, including breast, gastrointestinal, hepatobiliary, and ovarian. The use of antimetabolites in cancer therapy has generally not been associated with leukemogenesis. In this report, we demonstrate a case of capecitabine-related acute myeloid leukemia that was diagnosed 16 months after the completion of treatment for early-stage colon cancer, by a complex chromosome analysis 48,XY,6,del(7)(q22),+8,+13,t(13;17)(q12;p13),t(13,21)(q12;122),+mar [Gazi Med J. 2018 Jan;29(1):57–58]. This is the first report to our knowledge of the development of t-AML in a patient with early-stage colon cancer that was caused by capecitabine. We should use capecitabine with caution. Further studies are essential to investigate capecitabine-triggered leukemogenesis.

Type of 5-fluorouracil and risk of cardiovascular events in early-stage colon cancer.

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.

An Early-Stage Colon Cancer Develops Intrabiliary Growth Type Metastasis 7 Years After Curative Colectomy

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.

Effect of sidedness on survival among patients with early-stage colon cancer: a SEER-based propensity score matching analysis

Background Most previous studies compared survival between left-sided and right-sided colon cancer without adjustment for clinicopathological parameters. We investigated the effect of sidedness on survival among patients with early-stage colon cancer, using a propensity score matching method. Methods The 18 registry custom data within the SEER database were used to identify patients who were diagnosed with colon cancer between 2010 and 2014. A propensity score matching analysis was performed using the nearest neighbor method. Survival was estimated using the Kaplan–Meier method. A Cox proportional hazards model was applied to determine the prognostic factors. Results In the unmatched cohort, 25,094 (35.72%) patients were diagnosed with left-sided colon cancer and 45,156 (64.28%) with right-sided colon cancer. After propensity score matching, each cohort included 5118 patients, and the clinicopathological characteristics were well balanced. In the unmatched cohort, left-sided colon cancer had superior all-cause (χ2=315, P<0.01) and cancer-specific (χ2=43, P<0.01) survival than right-sided tumors. However, in the matched cohort, no difference was observed for all-cause (χ2=0.7, P=0.4) and cancer-specific (χ2=0, P=0.96) survival between left and right colon cancer. The Cox model did not indicate sidedness as a prognostic factor. In the subgroup analysis, stage II right-sided colon cancer had a better survival outcome, while stage III left-sided tumors had a better survival outcome. Conclusions After adjusting for clinicopathological characteristics in this study, sidedness showed no impact on survival in early-stage colon cancer. However, sidedness was associated with prognostic differences in stages II and III early-stage colon cancer.

PD-L1 as a Prognostic Factor in Early-Stage Colon Carcinoma within the Immunohistochemical Molecular Subtype Classification

Background. There is a patent need to better characterize early-stage colorectal cancer (CRC) patients. PD-1 ligand (PD-L1) expression has been proposed as a prognostic factor but yields mixed results in different settings. The Consensus Molecular Subtype (CMS) classification has yet to be integrated into clinical practice. We sought to evaluate the prognostic value of PD-L1 expression overall and within CMS in early-stage colon cancer patients, in the hope of assisting treatment choice in this setting. Methods. Tissue-microarrays were constructed from tumor samples of 162 stage II/III CRC patients. They underwent automatic immunohistochemical staining for PD-L1 and the proposed CMS panel. Primary endpoints were overall survival (OS) and disease-free survival (DFS). Results. PD-L1 expression was significantly and independently associated with better prognosis (HR = 0.46 (0.26–0.82), p = 0.009) and was mostly seen in immune cells of the tumor-related stroma. CMS4 five-folds the risk of mortalitycompared with CMS1 (HR = 5.58 (1.36, 22.0), p = 0.034). In the subgroup CMS2/CMS3 analysis, PD-L1 expression significantly differentiated individuals with better OS (p = 0.004) and DFS (p < 0.001). Conclusions. Our study suggests that PD-L1 expression is an independent prognostic factor in patients with stage II/III colon cancer. Additionally, it successfully differentiates patients with better prognosis in the CMS2/CMS3 group and may prove significant for the clinical relevance of the CMS classification.