Treatment Of Colon Cancer Patients Research Articles

9P Positive ad hoc results from neoadjuvant Foxy-5 treatment of colon cancer patients in the ongoing phase II NeoFox study

9P Positive ad hoc results from neoadjuvant Foxy-5 treatment of colon cancer patients in the ongoing phase II NeoFox study

Sulfotransferase SULT2B1 facilitates colon cancer metastasis by promoting SCD1-mediated lipid metabolism.

Metastasis is responsible for at least 90% of colon cancer (CC)-related deaths. Lipid metabolism is a critical factor in cancer metastasis, yet the underlying mechanism requires further investigation. Herein, through the utilisation of single-cell sequencing and proteomics, we identified sulfotransferase SULT2B1 as a novel metastatic tumour marker of CC, which was associated with poor prognosis. CC orthotopic model and in vitro assays showed that SULT2B1 promoted lipid metabolism and metastasis. Moreover, SULT2B1 directly interacted with SCD1 to facilitate lipid metabolism and promoted metastasis of CC cells. And the combined application of SCD1 inhibitor CAY with SULT2B1- konockout (KO) demonstrated a more robust inhibitory effect on lipid metabolism and metastasis of CC cells in comparison to sole application of SULT2B1-KO. Notably, we revealed that lovastatin can block the SULT2B1-induced promotion of lipid metabolism and distant metastasis in vivo. Further evidence showed that SMC1A transcriptionally upregulated the expression of SULT2B1. Our findings unveiled the critical role of SULT2B1 in CC metastasis and provided a new perspective for the treatment of CC patients with distant metastasis.

Identifying important microbial biomarkers for the diagnosis of colon cancer using a random forest approach

Colon cancer is one of the most common cancers, with 30–50 % of patients returning or metastasizing within 5 years of treatment. Increasingly, researchers have highlighted the influence of microbes on cancer malignant activity, while no studies have explored the relationship between colon cancer and the microbes in tumors. Here, we used tissue and blood samples from 67 colon cancer patients to identify pathogenic microorganisms associated with the diagnosis and prediction of colon cancer and evaluate the predictive performance of each pathogenic marker and its combination based on the next-generation sequencing data by using random forest algorithms. The results showed that we constructed a database of 13,187 pathogenic microorganisms associated with human disease and identified 2 pathogenic microorganisms (Synthetic.construct_32630 and Dicrocoelium.dendriticum_57078) associated with colon cancer diagnosis, and the constructed diagnostic prediction model performed well for tumor tissue samples and blood samples. In summary, for the first time, we provide new molecular markers for the diagnosis of colon cancer based on the expression of pathogenic microorganisms in order to provide a reference for improving the effective screening rate of colon cancer in clinical practice and ameliorating the personalized treatment of colon cancer patients.

COL10A1 is a potential immunotherapy biomarker associated with immune infiltration and deficient mismatch repair in colon cancer.

Aim: Our study aimed to identify the role of COL10A1 in colon cancer, including interaction with immune infiltrates and somatic mutations. Methods: COL10A1 expression and prognostic value were assessed. Correlations between COL10A1 and various immune parameters were conducted by bioinformatic analysis. Results: Our study demonstrated that COL10A1 is overexpressed in colon cancer and correlates with poor patient survival. The expression level of COL10A1 is significantly associated with mismatch repair deficiency and immune infiltration. High expression of COL10A1 may confer greater sensitivity to anti-PD-1 treatment in colon cancer patients. Conclusion: COL10A1 is a potential diagnostic biomarker associated with deficient mismatch repair and immune infiltration in colon cancer.

Construction of a Risk Model for Colon Cancer Prognosis Based on Ubiquitin-Related Genes.

Colon cancer is a frequently developed malignancy from the digestive system that leads to poor prognosis of patients due to its high recurrence and high metastasis. Dysregulation of ubiquitin-mediated signaling can result in tumor formation and metastasis. We aimed to develop prognostic markers related to ubiquitination in colon cancer and a risk assessment model based on these markers to improve the prognosis of colon cancer patients. We constructed a prognosis-related model by performing differential expression analysis on ubiquitin-related genes in colon cancer patients based on public data and then undertaking Cox analysis, which selected 7 ubiquitin-related prognostic genes (TRIM58, ZBTB7C, TINCR, NEBL, WDR72, KCTD9, and KLHL35). The samples were divided into high and low RiskScore groups according to the risk assessment model, and as Kaplan-Meier suggested, the overall survival of patients with high RiskScore was prominently lower than that of patients with low RiskScore. The accuracy of RiskScore was assessed by receiver operating characteristic curves. Accordingly, the area under the curve values of 1-, 3-, and 5-year were 0.76, 0.74, and 0.77 in the training set and 0.67, 0.66, and 0.74 in the validation set, respectively. These data confirmed the preferable performance of this prognostic model in predicting colon cancer patients' prognoses. The relationship between this RiskScore and clinicopathological factors of colon cancer patients was analyzed via stratification. Univariate and multivariate Cox regression analyses were performed to determine whether this RiskScore could be applied as an independent prognostic factor. Finally, in order to better apply the prognostic model in clinical practice, we constructed an overall survival nomogram for colon cancer patients' prognoses based on clinical factors and RiskScores, which has preferable prediction accuracy and is better than the traditional tumor, node, and metastasis (TNM) staging system. The overall survival nomogram for prognosis can assist clinical oncologists to make a more accurate evaluation of patients' prognosis, as well as the implementation of individualized diagnosis and treatment for colon cancer patients.

Application of CRISPR-Cas9 gene editing technology in basic research, diagnosis and treatment of colon cancer.

Colon cancer is the fourth leading cause of cancer death worldwide, and its progression is accompanied by a complex array of genetic variations. CRISPR/Cas9 can identify new drug-resistant or sensitive mutations in colon cancer, and can use gene editing technology to develop new therapeutic targets and provide personalized treatments, thereby significantly improving the treatment of colon cancer patients. CRISPR/Cas9 systems are driving advances in biotechnology. RNA-directed Cas enzymes have accelerated the pace of basic research and led to clinical breakthroughs. This article reviews the rapid development of CRISPR/Cas in colon cancer, from gene editing to transcription regulation, gene knockout, genome-wide CRISPR tools, therapeutic targets, stem cell genomics, immunotherapy, metabolism-related genes and inflammatory bowel disease. In addition, the limitations and future development of CRISPR/Cas9 in colon cancer studies are reviewed. In conclusion, this article reviews the application of CRISPR-Cas9 gene editing technology in basic research, diagnosis and treatment of colon cancer.

The Use of Endo-Cellulase and Endo-Xylanase for the Extraction of Apple Pectins as Factors Modifying Their Anticancer Properties and Affecting Their Synergy with the Active Form of Irinotecan.

Pectin constitutes an essential component of dietary fiber. Modified pectins from various sources possess potent anticancer and immunomodulatory activities. In this study, two pectins isolated from apple pomace by Trichoderma enzyme treatment, PX (with endo-xylanase) and PCX (with both endo-cellulase and endo-xylanase), were studied in colon cancer cell lines (HCT 116, Caco-2, and HT-29). Both pectins reduced colon cancer cell viability, induced apoptosis, and increased intracellular amounts of reactive oxygen species. Additionally, synergy between pectin and an active form of irinotecan, SN-38, in all aspects mentioned above, was discovered. This drug is a common component of cytotoxic combinations recommended as treatment for colon cancer patients. PX and PCX demonstrated significant anti-inflammatory activity in lipopolysaccharide-stimulated cells. Interaction of apple pectins with galectin-3 and Toll-like Receptor 4 (TLR4) was suggested to be responsible for their anticancer and anti-inflammatory effect. Since PCX was more active than PX in almost all experiments, the role of the enzyme used to obtain the pectin for its biological activity was discussed. It was concluded that co-operation between both enzymes was needed to obtain the molecule of the most beneficial properties. The low molecular mass of PCX together with a high proportion of rhamnogalacturonan I (RG I) regions seemed to be crucial for its superior activity.

The Influence of Several Biological Parameters on the Management of Patients with Colon Cancer Undergoing Elective Surgery

(1) Aim of the study: Our study aims to analyze the influence of biological parameters such as hemoglobin, albumin, total protein, on the management and duration of treatment of colon cancer patients who have undergone elective surgery. (2) Material and methods: Data of 147 patients from the Surgery Clinic 1 of the County Clinical Hospital of Timisoara who underwent an elective surgery for colon cancer treatment were statistically analyzed using statistical tests such as Anova or Chi square with a p < 0.05 considered to be statistically significant. (3) Results: Differences between preoperative and postoperative parameters were correlated with the duration of surgery (hemoglobin, p = 0.014). The average length of hospital stay was correlated with the difference between the preoperative and postoperative level of hemoglobin (p = 0.043). There was a direct correlation between the length of postoperative hospital stay and the difference between the plasmatic levels of albumin (p = 0.033). There were differences in the average Charlson index value of patients who required albumin, with no statistical significance. (4) Conclusions: The difference between preoperative and postoperative levels of biological parameters (hemoglobin, albumin, total protein) has an influence on the management of patients with colon cancer undergoing elective surgery, affecting the number of days the patients spend in the hospital after the surgical procedure, as well as the total number of days spent in the hospital (from day one to discharge). The greater the variation of those differences, the longer recovery period needed, showing that an early correction of those parameters can lead to a shorter hospital stay, a faster postoperative recovery and a shorter postoperative hospital stay.

Effect of pentoxifylline on colon cancer patients treated with chemotherapy (Part I).

Cancer progression is associated with significant systemic clinical manifestations including cachexia induced weight loss and anorexia. Pentoxifylline (PTX) is a drug that has been shown to have multiple beneficial effects in cancer patients through its anti-inflammatory properties. To evaluate PTX effects on colon cancer patients treated with chemotherapy. Forty metastatic colon cancer patients receiving chemotherapy were enrolled in this randomized study. 17 patients were treated with a full dose of PTX (400 mg TID), 9 patients with a reduced dose PTX (200 mg TID) and 23 served as controls (no PTX). Follow-up evaluations of patients included the following: physical examination; leukopenia determination; weight determination; stomatitis determination; and survival rate. Patients treated with PTX (both full and reduced doses), experienced a significant increase in weight and a reduction in stomatitis relative to the control group. Treatment with PTX also significantly increased patient survival rate. All patients treated with PTX, had a median overall survival (OS) rate of 20.4 months as compared to 13.2 months in the control group. PTX treatment of colon cancer patients, in addition to chemotherapy, significantly improved survival rates, induced weight gain and reduced stomatitis occurrence -all important parameters of cachexia.

Design, synthesis, molecular modelling and antiproliferative evaluation of novel benzothiazole trihybrids

Colorectal cancer is the third most commonly occurring cancer with very less treatment options in case surgery fails to cure the disease. The emergence of drug resistant colon cancer poses a new threat and calls for better drugs for treatment of colon cancer patients. Novel substituted benzo[d]thiazol-2-yl)-5-(pyridin-2-yl) penta-1,4-dien-3-one trihybrid molecules were synthesized following appropriate synthetic route. These compounds were tested for their efficacy in colon cancer and drug resistant colon cancer cell lines. Their toxicity was studied on the ICR mice model and the selectivity study was performed in calorimetric assay and xenograft mice model. An attempt was also made to chalk out the feasible mechanism of action based on molecular docking and molecular dynamics simulation studies. Compounds 4f, 4h and 4i were found to be highly effective and selective towards the inhibition of the colon cancer and drug resistant colon cancer cell lines and in the xenograft method. Selective compounds from this study can be developed into potential drug candidates for the possible treatment of drug resistant colorectal cancer.

Application of Nanobubble-Based Ultrasound Combined with General Anesthesia for the Treatment of Colon Cancer Patients

The nanobubble has recently become a new method to diagnose tumors. In this paper, nanobubble was prepared as follows. First, distearoylphosphatidylcholine and polyethylene glycol-distearyl phosphatidyl ethanolamine were dissolved in 8:1 chloroform/ethanol, and then PBS buffer was added, followed by ultrasonic dispersion for 30 s, and a 65 °C water bath to completely evaporate the organic solvent. Next, 1.5 mL liposome suspension obtained was transferred in a 5 mL conical flask, with 2.5 mL perfluoropropane injected, followed by sonication for 1 min. Finally, the nanobubble was obtained. In this study, 30 patients with colon cancer who underwent radical resection of colon cancer divided into 2 groups with 15 patients in each group. Controls were treated with sham irradiation, while ultrasonic treatment group (DUS treatment group) was treated with ultrasonic irradiation (1 W/cm2 + 3 min) combined with intravenous injection of nanobubbles. The outcome indexes of the two groups were recorded before anesthesia induction (T1), after surgery (T2), 3 days after surgery (T3), and 7 days after surgery (T4). It was found that, the concentration of nanobubble was 1.5 × 108/mL, and the average particle size was 457.23 ±6.24 nm. Control group and DUS treatment group had lower heart rates (HR) at T2 versus that at T1 (P < 0.05). Also, the mean arterial pressure (MAP) of two groups at T2 (89.67±8.69 mmHg, 96.24 ±8.54 mmHg) was also lower versus that at T1 (P < 0.05). For the saturation of central venous oxygen (ScvO2), O2 transport index (DO2I), and O2 consumption index (VO2I) of two groups, the values at time T2–T4 were all superior to those at time T1 (P < 0.05). Ultrasonic technology based on nanobubble combined with general anesthesia can better maintain the stability of hemodynamics during surgery than conventional ultrasound.

Nanomedicines in the treatment of colon cancer: a focus on metallodrugs.

Worldwide, colon cancer (CC) represents the fourth most common type of cancer and the fifth major cause of cancer-associated deaths. Surgical resection is considered the standard therapeutic choice for CC in early stages. However, in latter stages of the disease, adjuvant chemotherapy is essential for an appropriate management of this pathology. Metal-based complexes displaying cytotoxic properties towards tumor cells emerge as potential chemotherapeutic options. One metallodrug, oxaliplatin, was already approved for clinical use, playing an important role in the treatment of CC patients. Unfortunately, most of the newly designed metal-based complexes exhibit lack of selectivity against cancer cells, low solubility and permeability, high dose-limiting toxicity, and emergence of resistances. Nanodelivery systems enable the incorporation of metallodrugs at adequate payloads, solving the above-referred drawbacks. Moreover, drug delivery systems, depending on their physicochemical properties, are able to release the incorporated material preferentially at affected tissues/organs, enhancing the therapeutic activity in vivo, with concomitant fewer side effects. In this review, the general features and therapeutic management of CC will be addressed, with a special focus on preclinical or clinical studies using metal-based compounds. Furthermore, the use of different nanodelivery systems will also be described as tools to potentiate the therapeutic index of metallodrugs for the management of CC.

Staging Paradox and Discrepancy in Adjuvant Chemotherapy in Patients with T4N0, T1‐2N1, and T3N1 Colon Cancer

A survival paradox between T4N0 (stage IIB/C) and T3N1 (stage IIIB) colon cancer has been rarely reported. The indication and regimen of adjuvant chemotherapy are separately described in the guidelines. This study aimed to elucidate the prognostic factors and investigate proper adjuvant treatment in colon cancer patients at these stages. Patients who underwent R0 resection for pathological T4N0 (n = 49), T1-2N1 (n = 31), or T3N1 (n = 82) colon cancer between 2008 and 2016 at a single institute were retrospectively reviewed. The clinicopathological characteristics, status of adjuvant chemotherapy, and oncologic outcomes of patients with T4N0 tumors were compared with those of patients with T1-2N1 and T3N1 tumors. The biological characteristics of T4N0 tumors were more aggressive compared with the characteristics of T1-2N1 tumors and were similar to those of T3N1 tumors. The usage rate of oxaliplatin as an adjuvant chemotherapy was significantly lower in T4N0 patients than in T1-2N1 and T3N1 patients. The rate of local recurrence was the highest in patients with T4N0 tumors, and the survival outcomes for patients with T4N0 tumors were significantly worse compared with those of T1-2N1 patients and were similar to those of T3N1 patients. A multivariate analysis revealed that lack of adequate use of oxaliplatin for adjuvant chemotherapy was the only prognostic factor. T4N0 colon cancer had similar oncological characteristics and survival outcomes to T3N1 colon cancer. Systematic adjuvant chemotherapy, including oxaliplatin, should be incorporated into the therapy for T4N0 patients as well as T3N1 patients.

Transcription factor expression as a predictor of colon cancer prognosis: a machine learning practice

BackgroundColon cancer is one of the leading causes of cancer deaths in the USA and around the world. Molecular level characters, such as gene expression levels and mutations, may provide profound information for precision treatment apart from pathological indicators. Transcription factors function as critical regulators in all aspects of cell life, but transcription factors-based biomarkers for colon cancer prognosis were still rare and necessary.MethodsWe implemented an innovative process to select the transcription factors variables and evaluate the prognostic prediction power by combining the Cox PH model with the random forest algorithm. We picked five top-ranked transcription factors and built a prediction model by using Cox PH regression. Using Kaplan-Meier analysis, we validated our predictive model on four independent publicly available datasets (GSE39582, GSE17536, GSE37892, and GSE17537) from the GEO database, consisting of 925 colon cancer patients.ResultsA five-transcription-factors based predictive model for colon cancer prognosis has been developed by using TCGA colon cancer patient data. Five transcription factors identified for the predictive model is HOXC9, ZNF556, HEYL, HOXC4 and HOXC6. The prediction power of the model is validated with four GEO datasets consisting of 1584 patient samples. Kaplan-Meier curve and log-rank tests were conducted on both training and validation datasets, the difference of overall survival time between predicted low and high-risk groups can be clearly observed. Gene set enrichment analysis was performed to further investigate the difference between low and high-risk groups in the gene pathway level. The biological meaning was interpreted. Overall, our results prove our prediction model has a strong prediction power on colon cancer prognosis.ConclusionsTranscription factors can be used to construct colon cancer prognostic signatures with strong prediction power. The variable selection process used in this study has the potential to be implemented in the prognostic signature discovery of other cancer types. Our five TF-based predictive model would help with understanding the hidden relationship between colon cancer patient survival and transcription factor activities. It will also provide more insights into the precision treatment of colon cancer patients from a genomic information perspective.

Abstract 1475: Blockade of IL17-GCSF-Bv8 inflammation axis ameliorate resistant to anti-angiogenic therapy for colon cancer

Abstract Anti-angiogenic therapy in combination with chemotherapy is one of the standard strategies for metastatic/unresectable colon cancers. Therefore, resistance to anti-angiogenic therapy causes a critical problem for the treatment of colon cancer patients. While some resistant mechanisms of anti-angiogenic therapy were proposed, it is not yet completely unveiled. The aim of this study was to investigate the resistant mechanism against anti-angiogenic therapy using spontaneous colon cancer mouse models. We established a mouse model of anti-VEGF resistant colon cancer. Genetically-engineered Apc/Smad4 knockout mice developed several intestinal tumors that are sensitive to anti-VEGF neutralizing antibody. When Apc/Smad4 mice were treated with dextran sulfate sodium (DSS) (DSS-Apc/Smad4 mice), they developed colon tumors that were resistant to anti-VEGF antibody. Sera from DSS-Apc/Smad4 mice showed significant upregulation of granulocyte-colony stimulating factor (GCSF) compared to water-drinking Apc/Smad4 mice. Colon tumors from DSS-Apc/Smad4 mice also showed GCSF upregulation. It also showed upregulation of IL17, one of inflammatory cytokines upstream of GCSF, and Bv8, one of angiogenic factors downstream of GCSF, suggesting that IL17-GCSF-Bv8 inflammation axis contributes to obtaining anti-VEGF resistant. Immunostaining of the tumors from DSS-Apc/Smad4 mice revealed significant accumulation of neutrophils in the tumors. Neutrophils from tumor-bearing mice showed upregulation of Bv8 expression when stimulated with GCSF. Immunostaining confirmed that neutrophils in the tumors were positive for Bv8. When DSS-Apc/Smad4 mice were treated with either anti-IL17, anti-GCSF, or anti-BV8 neutralizing antibody in combination with anti-VEGF antibody, colonic tumor formation was significantly suppressed. We also performed ELISA analysis using human serum samples from subcohort of AVF2107 trial in which metastatic colon cancer patients were treated with chemotherapy (IFL with or without bevacizumab). Higher Bv8 serum levels by ELISA were significantly correlated with poor overall survival in human colon cancer patients. Collectively, inflammatory neutrophils in the tumor microenvironment of colon cancer provide anti-VEGF resistant through IL17-GCSF-Bv8 axis, and blockade of this pathway ameliorate resistance to anti-angiogenic therapy of colon cancer mouse models. Citation Format: Yoshiro Itatani, Takamasa Yamamoto, Napoleone Ferrara. Blockade of IL17-GCSF-Bv8 inflammation axis ameliorate resistant to anti-angiogenic therapy for colon cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1475.

Identification of an Immune-Related Nine-lncRNA Signature Predictive of Overall Survival in Colon Cancer.

Growing evidence suggests that immune-related genes (IRGs) and long non-coding RNAs (lncRNAs) can serve as prognostic markers of overall survival (OS) in patients with colon cancer. This study aimed to identify an immune-related lncRNA signature for the prospective assessment of prognosis in these patients. Gene expression and clinical data of colon cancer patients were downloaded from The Cancer Genome Atlas (TCGA). Immune-related lncRNAs were identified by a correlation analysis between IRGs and lncRNAs. In total, 447 samples were divided into a training cohort (224 samples) and a testing cohort (223 samples). Univariate, lasso and multivariate Cox regression analyses identified an immune-related nine-lncRNA signature closely related to OS in colon cancer patients in the training dataset. A risk score formula involving nine immune-related lncRNAs was developed to evaluate the prognostic value of the lncRNA signature in the training dataset. Colon cancer patients with a high risk score had poorer OS than those with a low risk score. A multivariate Cox regression analysis confirmed that the immune-related nine-lncRNA signature could be an independent prognostic factor in colon cancer patients. The results were further confirmed in the testing cohort and the entire TCGA cohort. Furthermore, a gene set enrichment analysis revealed several pathways with significant enrichment in the high- and low-risk groups that may be helpful in formulating clinical strategies and understanding the underlying mechanisms. Finally, a quantitative real-time polymerase chain reaction assay found that the nine lncRNAs were significantly differentially expressed in colon cancer cell lines. The results of this study indicate that this signature has important clinical implications for improving predictive outcomes and guiding individualized treatment in colon cancer patients. These lncRNAs could be potential biomarkers affecting the prognosis of colon cancer.

Translational Potential of MicroRNAs for Preoperative Staging and Prediction of Chemoradiotherapy Response in Rectal Cancer.

Colorectal cancer is the third most common cancer and the second cause of cancer-related deaths. Rectal cancer presents roughly one-third of all colorectal cancer cases and differs from it on both anatomical and molecular levels. While standard treatment of colon cancer patients is radical surgery, rectal cancer is usually treated with pre-operative chemoradiotherapy followed by total mesorectal excision, which requires precise estimation of TNM staging. Unfortunately, stage evaluation is based solely on imaging modalities, and they often do not correlate with postoperative pathological findings. Moreover, approximately half of rectal cancer patients do not respond to such pre-operative therapy, so they are exposed to its toxic effects without any clinical benefit. Thus, biomarkers that could precisely predict pre-operative TNM staging, and especially response to therapy, would significantly advance rectal cancer treatment—but till now, no such biomarker has been identified. In cancer research, microRNAs are emerging biomarkers due to their connection with carcinogenesis and exceptional stability. Circulating miRNAs are promising non-invasive biomarkers that could allow monitoring of a patient throughout the whole therapeutic process. This mini-review aims to summarize the current knowledge on miRNAs and circulating miRNAs involved in the prediction of response to treatment and pre-operative staging in rectal cancer patients.

Reversine inhibits Colon Carcinoma Cell Migration by Targeting JNK1

Colorectal cancer is one of the most commonly diagnosed cancers and the third most common cause of cancer-related death. Metastasis is the leading reason for the resultant mortality of these patients. Accordingly, development and characterization of novel anti-cancer drugs limiting colorectal tumor cell dissemination and metastasis are needed. In this study, we found that the small molecule Reversine reduces the migration potential of human colon carcinoma cells in vitro. A coupled kinase assay with bio-informatics approach identified the c-Jun N-terminal kinase (JNK) cascade as the main pathway inhibited by Reversine. Knockdown experiments and pharmacological inhibition identified JNK1 but not JNK2, as a downstream effector target in cancer cell migration. Xenograft experiments confirm the effect of JNK inhibition in the metastatic potential of colon cancer cells. These results highlight the impact of individual JNK isoforms in cancer cell metastasis and propose Reversine as a novel anti-cancer molecule for treatment of colon cancer patients.

Value of radiofrequency ablation combined with irinotecan and capecitabine chemotherapy in treatment of colon cancer patients with liver metastasis

Value of radiofrequency ablation combined with irinotecan and capecitabine chemotherapy in treatment of colon cancer patients with liver metastasis

The Influence of BRAF and KRAS Mutation Status on the Association between Aspirin Use and Survival after Colon Cancer Diagnosis.

BackgroundUse of aspirin after diagnosis of colon cancer has been associated with improved survival. Identification of cancer subtypes that respond to aspirin treatment may help develop personalized treatment regimens. The aim of this study was to investigate the influence of BRAF and KRAS mutation status on the association between aspirin use and overall survival after colon cancer diagnosis.MethodsA random selection of 599 patients with colon cancer were analyzed, selected from the Eindhoven Cancer Registry, and BRAF and KRAS mutation status was determined. Data on aspirin use (80 mg) were obtained from the PHARMO Database Network. Parametric survival models with exponential (Poisson) distribution were used.ResultsAspirin use after colon cancer diagnosis was associated with improved overall survival in wild-type BRAF tumors, adjusted rate ratio (RR) of 0.60 (95% CI 0.44–0.83). In contrast, aspirin use in BRAF mutated tumors was not associated with an improved survival (RR 1.11, 95% CI 0.57–2.16). P-value for interaction was non-significant. KRAS mutational status did not differentiate in the association between aspirin use and survival.ConclusionLow-dose aspirin use after colon cancer diagnosis was associated with improved survival in BRAF wild-type tumors only. However, the large confidence interval of the rate ratio for the use of aspirin in patients with BRAF mutation does not rule out a possible benefit. These results preclude BRAF and KRAS mutation status to be used as a marker for individualized treatment with aspirin, if aspirin becomes regular adjuvant treatment for colon cancer patients in the future.