Adjuvant Therapy For Colorectal Cancer Research Articles

Integrating UHPLC-Q-TOF-MS/MS, Network Pharmacology, Bioinformatics and Experimental Validation to Uncover the Anti-cancer Mechanisms of TiaoPi AnChang Decoction in Colorectal Cancer

Ethnopharmacological relevanceThe TiaoPi AnChang Decoction (TPACD), a Traditional Chinese Medicine (TCM) prescription based on Xiangsha Liujunzi Decoction, has demonstrated clinical efficacy as an adjuvant therapy for colorectal cancer (CRC) patients. However, its specific ingredients and potential mechanisms of action remain unclear. Aim of the studyTo identify the primary active ingredients of TPACD, their molecular targets, and potential mechanisms underlying the efficacy of TPACD in CRC treatment. Materials and methodsThis study investigated the clinically validated TCM formula TPACD. In vitro and in vivo experiments were used to demonstrate TPACD’s regulatory effects on various malignant phenotypes of tumors, providing basic research support for its anti-cancer activity. To understand its pharmacodynamic basis, we utilized ultra-high performance liquid chromatography-quadrupole-time-of-flight-mass spectrometry/mass spectrometry (UHPLC-Q-TOF-MS/MS) to analyze TPACD constituents present in the bloodstream. Network pharmacology and bioinformatics analyses were used to identify potential active components and their molecular targets for TPACD’s therapeutic effects in CRC. Subsequent experiments further elucidated its pharmacological mechanism. ResultsTPACD inhibits various malignant cellular processes, such as cell proliferation, apoptosis, migration, and invasion, and has shown potential anti-CRC activities both in vitro and in vivo. Following the identification of 109 constituents absorbed into the blood from TPACD, network pharmacology analysis predicted 42 potential anti-CRC targets. Clinical analyses highlighted three genes as prognostic key genes of TPACD’s therapeutic action: C-X-C motif chemokine ligand 8 (CXCL8), fatty acid binding protein 4 (FABP4), and matrix metallopeptidase 3 (MMP3). Drug sensitivity analyses, molecular docking simulations and reverse transcription-quantitative polymerase chain reaction (RT-qPCR) identified MMP3 as the most promising target for TPACD’s anti-CRC action. Enzyme activity assays confirmed that TPACD inhibits MMP3 enzyme activity. Surface plasmon resonance (SPR) characterized the binding affinity between MMP3 and effective active components of TPACD, including luteolin, quercetin, kaempferol, and liensinine. ConclusionsTPACD exhibits anti-CRC activity in vitro and in vivo, with MMP3 identified as a critical target. The active compounds, including luteolin, quercetin, kaempferol, and liensinine, absorbed into the bloodstream, contribute to TPACD's efficacy by targeting MMP3.

Thymoquinone: A Promising Therapeutic Agent for the Treatment of Colorectal Cancer.

Colorectal cancer (CRC) is one of the most commonly diagnosed cancers and is responsible for approximately one million deaths each year. The current standard of care is surgical resection of the lesion and chemotherapy with 5-fluorouracil (5-FU). However, of concern is the increasing incidence in an increasingly younger patient population and the ability of CRC cells to develop resistance to 5-FU. In this review, we discuss the effects of thymoquinone (TQ), one of the main bioactive components of Nigella sativa seeds, on CRC, with a particular focus on the use of TQ in combination therapy with other chemotherapeutic agents. TQ exhibits anti-CRC activity by inducing a proapoptotic effect and inhibiting proliferation, primarily through its effect on the regulation of signaling pathways crucial for tumor progression and oxidative stress. TQ can be used synergistically with chemotherapeutic agents to enhance their anticancer effects and to influence the expression of signaling pathways and other genes important in cancer development. These data appear to be most relevant for co-treatment with 5-FU. We believe that TQ is a suitable candidate for consideration in the chemoprevention and adjuvant therapy for CRC, but further studies, including clinical trials, are needed to confirm its safety and efficacy in the treatment of cancer.

Role of Single-Nucleotide Polymorphisms in Genes Implicated in Capecitabine Pharmacodynamics on the Effectiveness of Adjuvant Therapy in Colorectal Cancer.

Colorectal cancer (CRC) is a highly prevalent form of neoplasm worldwide. Capecitabine, an oral antimetabolite, is widely used for CRC treatment; however, there exists substantial variation in individual therapy response. This may be due to genetic variations in genes involved in capecitabine pharmacodynamics (PD). In this study, we investigated the role of single-nucleotide polymorphisms (SNPs) related to capecitabine's PD on disease-free survival (DFS) in CRC patients under adjuvant treatment. Thirteen SNPs in the TYMS, ENOSF1, MTHFR, ERCC1/2, and XRCC1/3 genes were genotyped in 142 CRC patients using real-time PCR with predesigned TaqMan® probes. A significant association was found between favorable DFS and the ENOSF1 rs2612091-T allele (p = 0.010; HR = 0.34; 95% CI = 0.14-0.83), as well as with the TYMS/ENOSF1 region ACT haplotype (p = 0.012; HR = 0.37; 95% CI = 0.17-0.80). Other factors such as low histological grade (p = 0.009; HR = 0.34; 95% CI = 0.14-0.79) and a family history of cancer (p = 0.040; HR = 0.48; 95% CI = 0.23-0.99) were also linked to improved DFS. Therefore, the SNP ENOSF1 rs2612091 could be considered as a predictive genetic biomarker for survival in CRC patients receiving capecitabine-based adjuvant regimens.

Exploring the pharmacological and molecular mechanisms of Salvia chinensis Benth in colorectal cancer: A network pharmacology and molecular docking study.

While Salvia chinensis Benth (commonly known as "Shijianchuan" in Chinese, and abbreviated as SJC) is commonly used in adjuvant therapy for colorectal cancer (CRC) in traditional Chinese medicine, its mechanism of action remains unclear. In this study, Initially, we examined the impact of SJC on CRC cells in an in vitro setting. Next, we initially retrieved the primary active components and targets of SJC from databases such as TCMSP and existing literature. Subsequently, we integrated differential gene expression data from the GEO database and collected CRC-related targets from resources like DisGeNET. The matching of these datasets enabled the identification of SJC-CRC targets. We constructed a protein-protein interaction network and identified core targets through topological analysis. GO and KEGG enrichment analyses were performed using clusterProfiler. We established networks linking traditional Chinese medicine components to targets and core targets to signaling pathways. Additionally, we performed molecular docking to validate interactions between the main compounds and targets, and employed Western blot analysis to explore how the major components of SJC affect crucial signaling pathways. In this study, SJC inhibited the viability of HCT-116 and HT-29 cells. We identified a total of 11 active components in SJC along with 317 target genes. Among these, there were 8612 target genes associated with CRC, and we successfully matched 276 SJC-CRC target genes. Through topological analysis of the protein-protein interaction network, we pinpointed 20 core targets. It was revealed that SJC effects are linked to genes governing processes like cell apoptosis, proliferation, hypoxia, oxidative stress, and signaling pathways such as PI3K-Akt through GO and KEGG pathway enrichment analyses. Additionally, we applied molecular docking techniques and observed that the majority of active compounds displayed robust binding affinity with the selected targets. In vitro experiments suggested that SJC and its key component, Ursolic acid, may exert its anti-CRC effects by modulating the core PI3K/AKT signaling pathway through inhibiting the phosphorylation of the target Akt1. This discovery is consistent with the predictions derived from network pharmacology methods. This study marks the inaugural utilization of bioinformatics methods in conjunction with in vitro experiments to comprehensively investigate the pharmacological and molecular mechanisms responsible for SJC anti-CRC effects.

Overuse of antibiotics: current situation and countermeasures

The birth history, role, current situation, and future prediction of antibiotics are summarized. The causes of antibiotic abuse and the harm of antibiotics are outlined through the existing antibiotic problems in society. Through the current data to analyze the solution to the problem of antibiotic abuse, how to avoid and how to treat it after abuse. Using scientific thinking methods such as induction generalization and critical thinking, deepen and apply the concept, understand the essence of biological evolution, and promote the achievement of the literacy of the biology discipline. theoretical and preclinical findings and its rate-limiting enzyme-related adjuvant therapy for colorectal cancer.

Role and progress of arginine and its rate-limiting enzyme in the treatment of colorectal cancer

The treatment for colorectal cancer presents a major challenge worldwide, ranking second to lung cancer in terms of yearly fatalities. Early detection and surgery are the mainstays of current treatment; additionally, adjuvant anticancer agents are imperative. There is controversy surrounding the use of arginine in treating colorectal cancer, with two main approaches: arginine deprivation and arginine supplementation. Arginine is essential for the development and progression of colorectal cancer. As a result, arginine deprivation therapy suggests that pegylated arginine deaminase (ADI-PEG) and pegylated human recombinant Arg-1 (rhArg1-PEG) supplements should be taken in the absence of argininosuccinate synthetase-1 (ASS1) and argininosuccinate lyase (ASL). This would further reduce the supply of exogenous arginine, which can effectively inhibit tumor development. Nevertheless, studies have revealed that low L-arginine levels in tumors restrict T cell activation and proliferation, which, in turn, reduces the immune response and negatively impacts tumor therapy—furthermore, colonizing MC38 tumors with ECN that produce.High levels of L-Arg combined with anti-PD-L1 antibody significantly improved the effectiveness of PD-L1-mediated immunotherapy. This paper reviews arginine’s theoretical and preclinical findings and its rate-limiting enzyme-related adjuvant therapy for colorectal cancer.

The Plausible Use of Mango (Mangifera indica) Peel Isoquercitrin as Adjuvant Therapy for Colorectal Cancer: Translating Research from Bench to Bedside

A deadly and debilitating disease, colorectal cancer (CRC), is rapidly becoming a significant threat to public health. However, current therapeutic approaches are still hampered by various side effects. Due to its benefits and remarkable apoptotic impact on cancer cells, plant-derived flavonoids now garner interest as candidates for cancer therapy. Isoquercitrin, a flavonoid commonly found in fruit plants, especially mangoes, is notable due to its ability to inhibit cancer development through various mechanisms. This review aims to highlight the use of isoquercitrin extracted from mango peels in inhibiting CRC carcinogenesis. A literature search was done on Pubmed, Proquest, and Google Scholar using inclusion and exclusion criteria, and a narrative review was synthesised using the evidence gathered. Validity assessment was done through the the Office of Health Assessment and Translation (OHAT) and Oxford Center for Evidence-Based Medicine (CEBM) critical assessment tools. Evidence suggested that isoquercitrin is promising as adjuvant therapy in CRC. It may inhibit overaccumulation of cytoplasmic β-catenin and its translocation into the nucleus, thus downregulating the expression of target proto-oncogenes leading to carcinogenesis of colon crypts. Isoquercitrin concentration in mango peel is abundant, 557.7 mg/kg in dried mango peel and 31.0 mg/kg in pure extracts. A pharmacology study approved that a daily intake of 5.4 mg/kgBW of isoquercitrin has an effective anticancer effect. This substance has good oral bioavailability and is well-tolerated but inhibits the metabolising enzymes CYP1A1 and CYP1B1. In conclusion, isoquercitrin is a potential adjuvant in inhibiting CRC growth with minimum costs and side effects.

Anti-tumor effects of Auraptene through induction of apoptosis and oxidative stress in a mouse model of colorectal cancer

The main strategy of cancer cells for survival is uncontrolled cell division and escape from apoptosis. The use of anticancer agents inducing the production of reactive oxygen species (ROS) and controlling cell division might be a therapeutic approach to eradicate cancer cells. Herein, we examined the therapeutic effects of Auraptene on CT26 cells as well as on a mouse model of colorectal cancer (CRC). The spheroid assay was also conducted to analyze the anti-proliferative activity of Auraptene. We also assessed the in vitro analysis of ROS generation. The impact of Auraptene on oxidant/antioxidant markers, as well as the mRNA expression of Bax, Bcl-2, Nrf2, Cyclin D1, and Survivin genes, was evaluated by qPCR in tumor samples. As a result, Auraptene significantly reduced the size of CT26 spheroids at a dose of 200 µM. After 12 h, ROS levels were significantly elevated in CT26 cells. The administration of Auraptene induced apoptosis and the cell cycle arrest by modulating Bax, Bcl-2, Nrf2, Cyclin D1, and Survivin mRNA levels. Furthermore, our results demonstrated that Auraptene suppressed CAT, GSH (reduced Glutathione), and FRAP while increasing MDA in tissue homogenates which in turn could raise oxidative stress and stimulate apoptosis. Therefore, Auraptene may act as a powerful adjuvant therapy in CRC since it triggers apoptosis and cell cycle.

Brassica juncea polysaccharides induce apoptosis of colorectal cancer cells via mitochondrial- and caspasedependent apoptosis pathways

Purpose: To determine the effect of polysaccharides from Gleditsia on apoptosis of colorectal cancer cells, and the mechanism involved.Methods: Polysaccharides were extracted from Lycium barbarum, and their concentration was more than 85 %. Then, DLD-1 cells were cultured in medium with the polysaccharides at concentrations of 75 and 150 μg/mL. Cell proliferation was determined with MTT (3-(4,5)-dimethylthiahiazo (-z-y1)-3,5- diphenytetrazoliumromide) assay and colony formation assay, while apoptosis was determined with flow cytometry. Changes in MMP were measured flow cytometrically. The protein levels of PARP, Bcl-2, Bax, and caspases 3 and 9 were determined with Western blot assay.Results: Cell viability decreased time-dependently. Compared with control without polysaccharide exposure, cell viability, colony forming cells, % apoptosis, red: green fluorescence ratio, and bcl-2 expression were significantly and concentration-dependently decreased, while the expression levels of PARP, Bax, caspase-3 and caspase-8 were significantly increased (p < 0.05).Conclusion: These results indicate that the polysaccharides suppressed apoptosis of colorectal cancer cells by inhibiting the mitochondrial and caspase-dependent apoptosis pathways. Gleditsia polysaccharide may be used as an adjuvant therapy for colorectal cancer.

A case in which TAS-102 produced disease control without severe adverse events in a patient with recurrent colorectal cancer and dihydropyrimidine dehydrogenase deficiency

Fluoropyrimidine is commonly used to treat unresectable cases of metastatic colorectal cancer or as an adjuvant therapy for colorectal cancer. Dihydropyrimidine dehydrogenase (DPD) is an enzyme encoded by the DPYD gene, which is responsible for the rate-limiting step in pyrimidine catabolism and breaks down >80% of standard doses of 5-fluorouracil (5-FU). Reductions in DPD activity increase the half-life of 5-FU, resulting in excess 5-FU accumulation and toxicity, which can lead to life-threatening side effects. There have been several published case reports about DPD deficiency in colorectal cancer patients from Western countries. However, case reports of DPD deficiency in Japanese colorectal cancer patients are rare because the measurement of DPD activity is not covered by the public medical insurance system in Japan, and DPD activity is not currently measured in daily clinical practice. Furthermore, there have not been any reports about anticancer drug therapy for Japanese patients with DPD deficiency. In this report, we describe a case in which a Japanese patient with colorectal cancer was diagnosed with DPD deficiency. The DPD deficiency arose as a severe adverse effect of mFOLFOX6/CapOX treatment for recurrent colorectal cancer, and the patient was subsequently treated with TAS-102, without experiencing any severe adverse effects. We report this case along with a review of the literature.

The comparison of FOLFOX regimens with different doses of 5-FU for the adjuvant treatment of colorectal cancer: a multicenter study.

We aim to compare the efficiency and toxicity of three different 5-fluorouracil (5-FU) administration types in 5-FU, leucovorin, and oxaliplatin (FOLFOX) combination treatment for adjuvant therapy in colorectal cancer (CRC). Five hundred and seventy patients with stage III colorectal carcinoma who received different FOLFOX regimens after curative resection were included. Patients were divided into three groups as FOLFOX-4, modified FOLFOX-6 (mFOLFOX-6), and mFOLFOX-4 for comparison of toxicity and disease-free survival (DFS) and overall survival (OS) times. Three-year DFS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 65%, 72%, and 72%, respectively. Five-year OS rates for FOLFOX-4, mFOLFOX-6, and mFOLFOX-4 groups were 69%, 75%, and 67%, respectively. There was no statistically significant difference between the three treatment groups in terms of DFS and OS (p = 0.079, and p = 0.147, respectively). Among grade 1-2 adverse events (AE), thrombocytopenia, neuropathy, and stomatitis were more common in the mFOLFOX-6-treated group. The frequency of grade 1-2 nausea and vomiting were similar in mFOLFOX-6 (36.3% and 24%, respectively) and mFOLFOX-4 (32.4% and 24.7%, respectively) groups but were higher than that in the FOLFOX-4 (19.5% and 11.3%, respectively) group. Among the most common grade 3-4 AE, neutropenia (53.4%, 9%, and 13.5%, respectively) and diarrhea (10.5%, 2.2%, and 2.4, respectively) were more common in FOLFOX-4. The rate of anemia and febrile neutropenia was similar in treatment groups (p = 0.063, and p = 0.210, respectively). In the adjuvant treatment of stage III CRC patients, three different 5-FU administration types in FOLFOX combination treatment can be used with similar efficiency and manageable toxicity.

CtDNA and Adjuvant Therapy for Colorectal Cancer: Time to Re-Invent Our Treatment Paradigm.

Simple SummaryThere is currently a lack of useful tests to detect microscopic residual disease in patients who have undergone surgery to remove their bowel cancer. This inability to identify patients with microscopic cancer could lead to over- and under-treatment with chemotherapy. Circulating tumour DNA (ctDNA) has shown significant promise to fill this gap to potentially personalize treatment after curative intent surgery allowing de-intensifying and intensifying of adjuvant therapies to reduce unnecessary toxicity of systemic therapy and also to hopefully cure more patients with ‘high risk of relapse’. This review article focuses on the current clinical use and future direction of ctDNA for early-stage bowel cancer.Colorectal cancer (CRC) is one of the leading causes of cancer-related deaths worldwide. While there have been significant developments in the treatments for patients with metastatic CRC in recent years, improving outcomes in the adjuvant setting has been more challenging. Recent technological advances in circulating tumour DNA (ctDNA) assay with the ability to detect minimal residual disease (MRD) after curative intent surgery will fundamentally change how we assess recurrence risk and conduct adjuvant trials. Studies in non-metastatic CRC have now demonstrated the prognostic impact of ctDNA analysis after curative intent surgery over and above current standard of care clinicopathological criteria. This ability of ctDNA analysis to stratify patients into low- and very-high-risk groups provides a window of opportunity to personalise adjuvant treatment where escalation/de-escalation of adjuvant systemic therapy could potentially increase cure rates and also reduce treatment-related physical and financial toxicity. Emerging data suggest that conversion of ctDNA from detectable to undetectable after adjuvant chemotherapy may reflect treatment efficacy. This real-time assessment of treatment benefit could be used as a surrogate endpoint for adjuvant novel drug development. Several ctDNA-based randomized adjuvant trials are ongoing internationally to confirm the clinical utility of ctDNA in colorectal cancer.

Thermosensitive hydrogels for local delivery of 5-fluorouracil as neoadjuvant or adjuvant therapy in colorectal cancer

Spurred by high risk for local tumor recurrence and non-specific toxicity of systemic chemotherapy, clinicians have recently granted a growing interest to locoregional therapeutic strategies. In this perspective, we recently developed a multipurpose thermosensitive hydrogel based on reversible thermogelling properties of poloxamers P407 and P188, a bioadhesive excipient and antineoplastic effect of 5-fluorouracil (5-FU) for the local treatment of colorectal cancer (CRC) in ectopic CT26 murine models. Antitumor efficacy was assessed in mice following intratumoral (IT) injection mimicking neoadjuvant therapy and subcutaneous (SC) application after tumor excision simulating adjuvant therapy. Rheological characterization disclosed that P407/P188/alginate 20/2/1% w/v thermosensitive hydrogel is an injectable free-flowing solution at ambient temperature that undergoes a SOL-GEL transition at 26.0 °C ± 0.6 °C and thereby forms in situ a non-flowing gel at physiological temperature. The generated gel presented an elastic behavior and responded according to a shear-thinning fluid upon shear rate. Although delayed by the addition of alginate 1% w/v, 5-FU is released mainly by diffusion mechanism. The local delivery of 5-FU from P407/P188/alginate/5-FU 20/2/1/0.5% w/v hydrogel in the preclinical tumor models led to a significant tumor growth delay. These results demonstrated that poloxamer-based thermosensitive hydrogels provide a simple and efficient means for local chemotherapeutics delivery.

Using low concentration sodium hypochlorite to improve colorectal surgical specimen lymph node harvest.

Lymph node (LN) retrieval is a critical procedure to determine the pathological stage and adjuvant therapy for colorectal cancer. The present study aimed to recommend a novel method by using sodium hypochlorite to improve colorectal surgical specimen LN harvest. Dissolving time of mesenteric LNs and fat tissue was firstly investigated in different concentrations of sodium hypochlorite. In the sodium hypochlorite group, 65 patients with colorectal cancer who underwent curative surgery were included. After standard manual gross dissection, the mesenteric tissue was subsequently immersed in 1% sodium hypochlorite for ~30 min, and then manual dissection was again applied for additional LN harvest. In the manual method group, 68 patients with colorectal cancer were selected and only manual dissection method was applied for LN harvest. The number of LNs in both groups were recorded for each case. Sodium hypochlorite could dissolve fat tissue significantly faster than LNs and the low concentration sodium hypochlorite had the maximum dissolving time difference between fat tissue and LNs (P<0.001). After sodium hypochlorite treatment, more LNs were identified when compared with the manual dissection method (28.2±12.1 vs. 16.5±8.7; P=0.010), whereas the number of positive LNs had no significant statistical difference between the two groups (P=0.181). After sodium hypochlorite immersion, 818 additional LNs (12.5±4.8 per case) were identified and LNs ≤2 mm were 58.4% (478/818). Moreover, 16 additional metastatic LNs were found in 10 patients. A total of 7 of them were upstaged, including 2 initially N0 cases. Using sodium hypochlorite at low concentrations may be the most simple, rapid, cost-saving, nontoxic and effective technique to improve LN harvest in colorectal carcinoma specimens so far. This method should be used routinely regardless of whether the number of LNs is <12 or not.

Consumption of Lactose, Other FODMAPs and Diarrhoea during Adjuvant 5-Fluorouracil Chemotherapy for Colorectal Cancer

Chemotherapy-induced mucosal injury of the small intestine may interfere with the enzymes and transporters responsible for the hydrolysis and absorption of dietary carbohydrates causing diarrhoea, abdominal discomfort and pain. The aim of this study was to investigate the association between the consumption of foods rich in FODMAPs (fermentable oligo-, di- and monosaccharides and polyols) and gastrointestinal symptoms in patients receiving adjuvant therapy for colorectal cancer. The patients (n = 52) filled in a 4-day food diary at baseline and during therapy and kept a symptom diary. The intakes of FODMAP-rich foods were calculated as portions and the intakes were divided into two consumption categories. Patients with high consumption of FODMAP-rich foods had diarrhoea more frequently than those with low consumption (for lactose-rich foods the odds ratio (OR) was 2.63, P = 0.03; and for other FODMAP-rich foods 1.82, P = 0.20). Patients with high consumption of both lactose-rich and other FODMAP-rich foods had an over 4-fold risk of developing diarrhoea as compared to those with low consumption of both (OR, 4.18; P = 0.02). These results were confirmed in multivariate models. Conclusion: Consumption of lactose-rich foods results in an increased risk of diarrhoea during adjuvant therapy for colorectal cancer, especially when the consumption of other FODMAP-rich foods is also high.

Essential advances in surgical and adjuvant therapies for colorectal cancer 2018-2019.

Surgical resection and adjuvant chemotherapy are the only treatment modalities for localized colorectal cancer that can obtain a “cure.” The goal in surgically treating primary colorectal cancer is complete tumor removal along with dissection of systematic D3 lymph nodes. Adjuvant treatment controls recurrence and improves the prognosis of patients after they undergo R0 resection. Various clinical studies have promoted the gradual spread and clinical use of new surgical approaches such as laparoscopic surgery, robotic surgery, and transanal total mesorectal excision (TaTME). Additionally, the significance of adjuvant chemotherapy has been established and it is now recommended in the JSCCR (the Japanese Society for Cancer of the Colon and Rectum) guideline as a standard treatment. Herein, we review and summarize current surgical treatment and adjuvant chemotherapy for localized colorectal cancer and discuss recent advances in personalized medicine related to adjuvant chemotherapy.

Oral adjuvant therapy for colorectal cancer: recent developments and future targets.

Colorectal cancer is considered the third most frequent malignant neoplasm occurring in both men and women worldwide. Most approaches that have been used to fight and treat this type of malignancy are either invasive or nonselective. Noninvasive therapy using oral route can increase patient compliance and reduce treatment costs. Innovative measures such as use of nanotechnology and theranostic systems have been initiated in the oral therapy, which has been proven to be greatly advantageous in decreasing side effects, improving detection and diagnoses. This manuscript investigates recent innovative and novel therapeutic approaches through oral route and potential targets in the treatment of colorectal cancer.

A nomogram to predict vascular invasion before resection of colorectal cancer.

Vascular invasion (VI) is an important feature for systemic recurrence and an indicator for the application of adjuvant therapy in colorectal cancer (CRC). Preoperative knowledge of VI is important in determining whether adjuvant therapy is necessary, as well as the adequacy of surgical resection. In the present study, a predictive nomogram for VI in patients with CRC was constructed. The prediction model consisted of 664 eligible patients with CRC, who were divided into a training set (n=468) and a validation set (n=196). Data were collected between August 2013 and April 2018. The feature selection model was established using the least absolute shrinkage and selection operator regression model. Multivariable logistic regression analysis was used to construct the predictive nomogram. The performance of the nomogram was evaluated by calibration, discrimination and clinical usefulness. Differentiation, computed tomography (CT)-based on N stage (CT N stage), hemameba and tumor distance from the anus (cm) were integrated into the nomogram. The nomogram exhibited good discrimination, with an area under the curve (AUC) of 0.731 and good calibration. Application of the nomogram in the validation cohort showed acceptable discrimination, with an AUC of 0.710 and good calibration. Decision curve analysis revealed that the nomogram was clinically useful. These findings suggests, to the best of our knowledge, that this may be the first nomogram for individual preoperative prediction of VI in patients with CRC, which may promote preoperative optimization strategies for this selected group of patients.

O-016 - Serial assessment of cell-free circulating tumor DNA (ctDNA) to assess treatment effect and minimal residual disease during neoadjuvant and adjuvant therapy in colorectal cancer

O-016 - Serial assessment of cell-free circulating tumor DNA (ctDNA) to assess treatment effect and minimal residual disease during neoadjuvant and adjuvant therapy in colorectal cancer

Cost minimization comparison of oral UFT/leucovorin versus 5-fluorouracil/leucovorin as adjuvant therapy for colorectal cancer in Taiwan.

Oral uracil-tegafur/leucovorin (UFT/LV) and intravenous 5-fluorouracil (FU)/LV are common adjuvant therapies for Stages II and III colorectal cancer. This study aims to determine the most cost-effective treatment alternative between UFT/LV and 5-FU/LV in Stages II and III colorectal cancer from Taiwan's National Health Insurance perspective. The costs were referenced directly from the National Health Insurance reimbursement price. Chemotherapy regimen considered for the cost analysis calculation was adapted from NSABP-C-06 study, and, a time saving calculation was also included. In addition, we compare the treatment outcome. A total cost saving of US$3620.80-$3709.16 per patient per treatment was achieved with the UFT/LV treatment. UFT/LV provides the comparable outcome to 5-FU/LV. UFT/LV was the more cost-effective treatment as adjuvant chemotherapy.