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Chemoradiation and Endothelial Progenitor Cells in Colorectal Cancer

ABSTRACT: Colorectal cancer (CRC) is one of the common malignancies worldwide, accounting for a significant percentage of cancer mortality. Concurrent chemoradiation (CCRT) is now a standard treatment for unresectable malignancies of anorectum. To improve quality of life, CCRT is also commonly applied in treatment of lower rectal and anal canal cancer to preserve anal sphincter function. The most commonly used chemotherapeutic drugs combined with radiation as radiosensitizers is 5-fluorouracil (5-FU). Circulating endothelial progenitor cells (EPC), which contribute to the tumor vessel formation, reflect the response to chemotherapy both in animal model and clinical trial. Thus, circulating EPC can be used as a marker for optimizing and monitoring the anti-angiogenesis therapy including angiogenesis inhibitors and chemotherapy. Whether circulating EPC can be served as a marker of CCRT efficacy or not remains undetermined. Since CCRT is now a standard treatment of locally advanced and high-risk CRC, the development of a surrogate marker for monitoring CCRT response and optimize treatment intensity is very important. In this grant we intent to monitor the levels of circulating EPC in locally advanced and high-risk CRC patients before, during and after CCRT. To further characterize the changes in function and biology of EPC caused by CCRT, a syngeneic animal model will be also used to evaluate the clonogenecity and specific gene expression of EPC in tumor-bearing mice receiving CCRT.

DISEASE(S): Colorectal Cancer,Colorectal Neoplasms

PROVIDER: 2028928 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:Fluoropyrimidines (FP) are the backbone chemotherapy in colorectal cancer (CRC) treatment; however, their use is associated with cardiotoxicity, which is underreported. In the present study, we aimed to prospectively determining the incidence rates and related risk factors of FP-induced cardiotoxicity (FIC) in CRC patients and at identifying predictive biomarkers. One hundred and twenty-nine consecutive previously untreated CRC patients underwent active cardiological monitoring, including 5-items simplified questionnaire on symptoms, electrocardiogram (ECG) and plasma sample collection during FP chemotherapy. FIC was defined as the presence of ECG alterations and/or the arising of at least one symptom of chest pain, dyspnoea, palpitations or syncope. The primary objective was the evaluation of FIC incidence. Secondary objectives were the correlation of FIC with well-known cardiological risk factors and the identification of circulating biomarkers (serum levels of TnI, proBNP; miRNA analysis) as predictors of FIC. Twenty out of 129 (15.5%) patients experienced FIC. The most common symptoms were dyspnoea (60%) and chest pain (40%), while only 15% of patients presented ECG alterations, including one acute myocardial infarction. Retreatment with FP was attempted in 90% of patients with a favourable outcome. Despite 48% of patients having cardiological comorbidities, we did not observe an increased FIC in this subgroup. Only the subgroup of females with the habit of alcohol consumption showed an increased risk of FIC. None of the circulating biomarkers evaluated demonstrated a clinical utility as FIC predictors. FIC can be an unexpected, life-threatening adverse event that can limit the subsequent treatment choices in CRC patients. In this prospective study, well-known cardiological comorbidities were not related to higher FIC risk and circulating biomarkers predictive of toxicity could not be found. With careful monitoring, mainly based on symptoms, almost all patients completed the FP treatment.

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Chemoradiation and Endothelial Progenitor Cells in Colorectal Cancer

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