Non-metastatic Colon Cancer Research Articles

Disparities in utilization of robotic surgery for colon cancer: an evaluation of the U.S. National Cancer Database.

Despite the benefits of minimally invasive surgery for colorectal procedures, significant disparities in access to these techniques remain. While these gaps have been well-documented for laparoscopy, few studies have evaluated inequalities in access to robotic surgery. We analyze whether disparities exist in the use of robotic surgery in the management of colon cancer. The U.S. National Cancer Database was queried for patients with non-metastatic colon adenocarcinoma who underwent resection with the robotic platform (2010-2016). Demographic, clinicopathologic, and treatment facility-related variables were analyzed with respect to preferential utilization of robotic surgery with multivariable logistic regression. Patients with metastatic disease, missing or incomplete surgical information, and those who underwent local tumor excision were excluded. 74,984 patients were identified, 3001 (4%) of whom underwent robotic surgery. In multivariable analysis, patients who were older, Black, or were living in an urban area had decreased odds of receiving robotic surgery compared with open or laparoscopic surgery. Patients who were privately insured or living in areas with higher education had increased odds of receiving robotic surgery. Robotic surgery was also preferentially associated with lower clinical stage, more recent year of diagnosis, and hospitals with higher procedural volume. As advantages of the robotic platform are becoming better understood, use of this approach is increasing in popularity for treatment of non-metastatic colon cancer. Despite this, significant disparities exist with respect to patient demographics and socioeconomic factors, and access may only be limited to certain types of hospitals. Further studies are needed to define why these inequalities exist.

Primary tumour immune response and lymph node yields in colon cancer

BackgroundThe mechanism underlying improved survival in non-metastatic colon cancer with higher lymph node (LN) yield is unknown. This study aimed to identify whether molecular features in the primary tumour were predictive of LN yield.MethodsClinical, genomic, transcriptomic, proteomic and methylation data of non-metastatic, colon cancers studied in The Cancer Genome Atlas were interrogated for associations with LN yield. Based on maximal survival effects, patients were segregated into high (>15) and low (≤15) LN yield. Gene set enrichment analysis was performed on transcriptomic changes to identify biological processes associated with LN yield. Correlations were validated in an independent set of Stage II colon cancers.ResultsHigh LN yield was found predictive of overall and disease-free survival. There was no association of higher LN yield and increasing nodal positivity. High LN yield was strongly linked with gene expression changes associated with the adaptive and dendritic cell immune response. This association was most prominent in node-negative cancers. Analogous findings were reproduced in the validation dataset.ConclusionThe study shows a strong association of an activated immune response in tumours with a high LN yield. Immunogenic tumours have a better prognosis, likely explaining the survival benefit with higher LN yields.

He effects of NETosis on fibrinolysis in colon cancer patients

Aim. To investigate formation of neutrophil extracellular traps (NETs) and their impact on fibrinolysis in patients with colon cancer.Materials and methods. The study was performed in two groups. The experimental group consisted of patients with stage 2–3 non-metastatic colon cancer (n = 17, average age – 67 years). The control group included healthy volunteers matched by sex and age (n = 30, average age – 68 years). An experimental model was created from the whole blood. It included platelet-poor plasma and an isolated culture of neutrophils, previously induced to NETosis by adding 100 nmol PMA. The samples were incubated for 4 hours, then the test tubes were centrifuged to pellet cells and their remnants, and the plasma was transferred for subsequent examination. The plasma incubated with intact neutrophils was used as a control. The levels of interleukin-8 (IL-8) and P-selectin glycoprotein ligand-1 (PSGL-1) were used to determine the degree of cell activation. NETosis was confirmed by enzyme-linked immunosorbent assay (ELISA) and fluorescent microscopy. Fibrinolysis was assessed using the thrombodynamics test. The results were compared with the levels of fibrinolytic system components measured by flow cytometry.Results. In the control group, NETosis induction contributed to pronounced neutrophil activation that was accompanied by an increase in the IL-8, PSGL-1, and plasminogen levels, a decrease in PAI-1, and enhancement of fibrinolysis, compared with the intact samples. Higher levels of IL-8, PSGL-1, plasminogen, and PAI-1 and intensified fibrinolysis were detected in the intact samples. However, PMA-induced NETosis did not result in an increase in the degree of activation and significant changes in the given parameters.Conclusion. NETosis promotes both formation and lysis of fibrin clots. However, in cancer patients, suicidal NETosis does not contribute to fibrinolysis due to intracellular protease depletion, which may be one of the mechanisms causing hypercoagulation and insufficient fibrinolysis in cancer.

Machine Learning-Based Prognostic Prediction Models of Non-Metastatic Colon Cancer: Analyses Based on Surveillance, Epidemiology and End Results Database and a Chinese Cohort.

PurposeThe present study aimed to develop prognostic prediction models based on machine learning (ML) for non-metastatic colon cancer (CRC), which can provide a precise quantitative risk assessment and serve as an assistive method for treatment strategy development. The possibility of improving prediction accuracy using nonlinear methods compared to linear methods was investigated.Patients and MethodsA cancer-specific survival (CSS) model constructed using logistic regression, extreme gradient boosting (XGBoost), and random forest algorithms was trained on the Surveillance, Epidemiology, and End Results datasets for 15,254 patients with non-metastatic CRC (split into training [70%] and internal validation [30%] datasets) and externally validated with an outpatient cohort of 311 cases from Xiyuan Hospital in China. A Chinese cohort was also used to develop recurrence and metastasis (R&M) models for CRC patients. The experiments for each model were performed 100 times to obtain average scores and 95% confidence intervals. The model performance was evaluated using the area under the receiver operating characteristic curve (AUC) values.ResultsThe XGBoost approach showed the highest AUC values of 0.86 (0.84–0.88), 0.82 (0.81–0.83), and 0.81 (0.79–0.82) for one-, three-, and five-year CSS cohorts, respectively, along with a relatively high generalization ability. The XGBoost approach also performed best for the R&M model, with the AUC values of 0.71 (0.64–0.79), 0.79 (0.74–0.86), and 0.89 (0.82–0.95) for one-, three-, and five-year R&M cohorts, respectively. The rankings of predictor importance for the CSS and R&M models were different, and the higher model accuracy was associated with more prognostic predictors.ConclusionThree different ML algorithms for developing prognostic prediction models for non-metastatic CRC were compared. The predictive performance results showed that the nonlinear XGBoost approach performed best, suggesting that it can be used for quantifying the prognostic risk. It was also demonstrated that the model performance can be improved when more prognostic predictors are considered.

Abstract PO-228: Racial disparities and the impact on recurrence and survival in non-metastatic colon cancer patients undergoing colectomy at a comprehensive cancer center

Abstract Introduction/Purpose: Colorectal cancer has worse outcomes among Black patients; however, few studies have evaluated differences in recurrence rates after surgery. Our goal was to compare recurrence between Black and white patients with colon cancer treated at a comprehensive cancer center with a standardized quality of care. Methods: A retrospective review of Black and white patients with Stage 0-III colon cancer undergoing surgical resection from 2006-2018 was conducted. Patients with neoadjuvant therapy, adjuvant radiation, and missing median family income or body mass index data were excluded. Demographic and clinical data were collected and compared between the groups. Median family income was estimated using patients' zip codes and Census data. Freedom from Recurrence (FFR) was the primary endpoint with an event defined as colon cancer recurrence. A Kaplan-Meier curve evaluated differences between the racial groups with a log-rank test to assess significance. A multivariable analysis using Cox proportional hazards was conducted, and a p value of <0.05 was considered significant. Results: Two thousand and sixty-one patients were included with 1912 white (93%) and 149 (7%) Black patients. Black patients had a median age of 61 compared with 65 in the white cohort (p=0.003) and had a higher median BMI prior to colectomy (p=0.01). Most had right-sided tumors in both groups (58% for Black and 50% for white patients; p=0.13). About 8% of Black patients had Medicaid insurance compared with 2% of white patients (p=<0.005), and Black patients had a lower estimated median family income (p=<0.005). On surgical pathology, more Black patients had node-positive disease (44% for Black and 33% for white patients; p=0.009) and received adjuvant chemotherapy (48% for Black and 37% for white patients; p=0.006). More Black patients underwent open colectomies (39% and 28% respectively, p=0.02). To assess resection quality, 5 white and 0 Black patients had positive margins, and the median total lymph node count was 25 for Black versus 23 for white patients (p=0.04). Few patients in each group had a colectomy with less than 12 lymph nodes resected (1% for Black and 4% for white patients; p=0.17). The survival analysis showed that white patients had a higher FFR compared to Black patients (p=0.005). However, only T4 classification (hazard ratio 2.03, confidence interval 1.52-2.71; p=<0.001) and node-positive disease (hazard ratio 2.88, confidence interval 2.20-3.79; p=<0.001) correlated with lower FFR on multivariable analysis. Race was not significantly correlated (hazard ratio of 1.47, confidence interval 0.97-2.23; p=0.07). Conclusion: We found significant differences in clinical and tumor characteristics between Black and white colon cancer patients who underwent resection consistent with more advanced presentation in Black patients. While Black patients were found to have a lower FFR, after controlling for other factors, Black and white patients had similar stage specific survival when treated at this comprehensive cancer center. Citation Format: Hannah M. Thompson, Jonathan B. Yuval, Anisha Luthra, Fan Wu, Tolulope Iwayemi, Iris H. Wei, Emmanouil P. Pappou, J. Joshua Smith, Garrett M. Nash, Julio Garcia-Aguilar, Francisco Sanchez-Vega. Racial disparities and the impact on recurrence and survival in non-metastatic colon cancer patients undergoing colectomy at a comprehensive cancer center [abstract]. In: Proceedings of the AACR Virtual Conference: 14th AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2021 Oct 6-8. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2022;31(1 Suppl):Abstract nr PO-228.

Nonmetastatic Colon Cancer Model C26 Upregulates Glycolysis in Osteocytes in Vitro and Bone in Vivo

Background: Developing effective treatments for musculoskeletal complications in cancer patients requires understanding metabolic effects of cancer on bone, and particularly osteocytes, the most abundant bone cell and key regulator of bone remodeling. However, little is known regarding how cancer impacts normal osteocyte energy metabolic pathways, such as glycolysis. Given that changes in metabolism are important regulators of cellular function, it is essential to determine how osteocyte metabolism is disrupted by cancer and how this may impact skeletal and whole-body health.
 Methods: Mice inoculated with saline (N=5) or C26 cells (N=6) were sacrificed after 2 weeks. Bones were harvested for metabolic profiling by GC-MS, gene expression by RT-PCR and bone morphology by µCT. Differentiated IDG-SW3 osteocyte-like cells were cocultured with C26 cells for 12-24hrs and metabolites and gene expression analyzed by GC-MS and RT-PCR.
 Results: Trabecular bone mass was significantly decreased in the C26 mice. GC-MS analysis revealed decreased glucose in C26 mice tibiae, but no change in lactate. The bone resorption promoting gene Rankl was upregulated, whereas the inhibitor Opg was unchanged. Bone mineralization regulators Mepe and Phex were decreased. In vitro metabolic studies revealed increased glucose and lactate in IDG-SW3 cell lysate; culture media glucose levels were decreased whereas lactate was increased in the co-cultures with C26 cells. RT-PCR demonstrated increases in the glycolysis promoter Hif1α in addition to glycolysis pathway genes including Glut1, Hk2, Slc16a3 and Pdk1. Rankl was also increased in the IDG-SW3 cells co-cultured with the C26 cells whereas Opg, Phex, and Mepe were downregulated.
 Conclusion: Glycolysis is upregulated in mouse bone and in vitro IDG-SW3 cells exposed to cancer. Our study provides novel understanding for how cancer affects bone metabolism. Integrating these results with whole body metabolism will aid in the development of novel therapeutic strategies to target musculoskeletal and systemic complications of cancer.

The impact of KRAS mutation, microsatellite instability, and tumor laterality on the prognosis of nonmetastatic colon cancer

BackgroundKRAS mutations, microsatellite instability, and tumor location have been found to be significant prognostic factors in colorectal cancer. The interaction between these variables and its effect on overall survival in nonmetastatic colon cancer has not been well elucidated. MethodsThe National Cancer Database (2010–2016) was queried for patients with stage I–III colon cancer and known microsatellite instability and KRAS status undergoing curative resection. ResultsA total of 5,292 patients were identified: 60.4% had right-sided cancers, 36.4% had KRAS mutations, and 15.6% had microsatellite instability. Right-sided tumors were more likely to have microsatellite instability and KRAS mutations compared to left-sided tumors. On univariable analysis, KRAS mutations and microsatellite instability status were not associated with differences in survival, whereas right-sided cancers had worse overall survival compared to left-sided cancers (hazard ratio 1.32, 95% confidence interval: 1.18–1.47). On multivariable analysis, right-sided location, KRAS mutations, and microsatellite instability were not independent prognostic factors. However, a significant interaction between laterality and KRAS status was observed. In patients with mutated KRAS cancers, left-sided tumors were at increased risk of death compared to right-sided tumors (hazard ratio: 1.30, 95% confidence interval: 1.03–1.63), whereas in patients with wild-type KRAS cancers, left-sided tumors were at decreased risk of death (hazard ratio: 0.81, 95% confidence interval: 0.67–0.97). ConclusionIn patients with stage I–III colon cancer, laterality, KRAS mutation, and microsatellite instability status were not independently prognostic after curative resection. However, the effect of laterality was opposite based on KRAS status, with left-sided (compared to right-sided) tumors associated with worse overall survival in mutated KRAS patients and better overall survival in wild-type KRAS individuals. Laterality itself may not be an independent prognostic factor but a reflection of differing genetic profiles within the colon.

Immediate Adjuvant Chemotherapy in Non-Metastatic Colon Cancer: Phase I Trial Evaluating a Novel Treatment Protocol

BackgroundThe optimal timing of adjuvant chemotherapy (AC) in non-metastatic colon cancer is poorly defined. Delays in AC result in decreased survival. Effective cytotoxic treatments should be considered during the perioperative phase of care. The immediate adjuvant chemotherapy (IAC) concept intends to capitalize on the therapeutic benefits that can be achieved in the perioperative period. We aim to demonstrate that IAC is safe and tolerable. Patient and MethodsMicrosatellite stable invasive adenocarcinomas were treated with intravenous Leucovorin 20 mg/m2 and single dose of 5-Flurouracil 400mg/m2 at the time of surgery. High-risk stage II and stage III received the first dose of standard AC at 14 days after surgery. Serial measurements of blood-based biomarkers were measured. Quality of life (QOL) was measured using EORTC QLQ-C30. ResultsOf the 20 patients recruited, 40% had final pathology of stage III, 40% stage II and 20% stage I. All patients received intra-operative chemotherapy with no associated morbidity. Median length of stay was 2 days (range of 2-4). There was no intraoperative morbidity with 5% (N = 1) grade 3 complication. AC was administered to 65% of patients. The median time to AC was 14 days (range 14-36). Overall quality of life and health scores were similar before surgery and at 30-day postoperatively (P < .05). ConclusionsA protocol based on IAC starting at the time of surgical resection was found to be safe and feasible with no adverse effects on surgical morbidity or quality of life. Further prospective studies are needed to explore the oncologic benefit of this novel systemic treatment approach.

Significance of preoperative blood tests in the prognosis of colorectal cancer: A prospective, multicenter study from Hungary.

BackgroundThe focus of this study was to analyze the prognostic value of different combinations of inflammatory and coagulation factors using preoperative blood and to appraise the clinical importance of these biomarkers in colorectal cancer patients.MethodsA prospective, multicenter study included patients undergoing radical colorectal surgery in three county hospitals. Inflammatory and coagulation markers were analyzed preoperatively.ResultsTwo hundred and one patients were included. We examined patients based on their tumor localization. Colon cancer group involved patients with the tumor localized in the colon (n = 105, 52.24%) and rectal cancer group the patients with the tumor in the rectum (n = 96, 47.76%). Examining coagulation factors, univariate Cox analysis of colon cancer patients showed that activated partial thromboplastin time (p = 0.020) was significantly associated with overall survival, but we could not prove it in multivariate analysis. In colon cancer patients, neutrophil‐to‐lymphocyte ratio (NLR, p < 0.001) was positively correlated with tumor size and had significant association (χ 2 = 5.48, p = 0.019, df = 1) with perineural invasion. Univariate and multivariate Cox analysis of colon cancer patients showed that NLR (p = 0.011 and p = 0.048) was significantly associated with disease‐free survival (DFS).ConclusionNLR was proved to be an independent prognostic factor for DFS in patients with non‐metastatic colon cancer. NLR might help to recognize the high‐risk patients between patients with the same tumor‐node‐metastasis stage and could help with the decision on adjuvant chemotherapy. Since the biomarkers in preoperative blood tests are habitually evaluated, NLR could be an inexpensive prognostic marker that can be easily assessed in clinical practice.

Myosteatosis Differentially Affects the Prognosis of Non-Metastatic Colon and Rectal Cancer Patients: An Exploratory Study

Body composition performed by computed tomography (CT) impacts on cancer patients’ prognoses and responses to treatment. Myosteatosis has been related to overall survival (OS) and disease-specific survival in colorectal cancer (CRC); however, the independent impact of the association of myosteatosis with prognosis in colon cancer (CC) and rectal cancer (RC) is still unclear. CT was performed at the L3 level to assess body composition features in 227 patients with CRC. Clinical parameters were collected. Overall survival (OS) was the primary outcome, and the secondary outcome was disease-free survival (DFS). Skeletal muscle attenuation and intramuscular adipose tissue area were associated with DFS (p = 0.003 and p = 0.011, respectively) and OS (p < 0.001 and p < 0.001, respectively) in CC patients but not in RC patients. Only the skeletal muscle area was associated with better prognosis related to OS in RC patients (p = 0.009). When CC and RC were analyzed separately, myosteatosis influenced survival negatively in CC patients, worsening DFS survival (hazard ratio [HR], 2.70; 95% confidence interval [CI], 1.07–6.82; p = 0.035) and OS (HR, 5.76; 95% CI, 1.31–25.40; p = 0.021). By contrast, the presence of myosteatosis did not influence DFS (HR, 1.02; 95% CI, 0.52–2.03; p = 0.944) or OS (HR, 0.76; 95% CI, 0.33–1.77; p = 0.529) in RC patients. Our study revealed the interference of myosteatosis in the therapy and survival of patients with CC but not in those with RC, strengthening the value of grouping the two types of cancer in body composition analyses.

Comparison of Vascular Invasion With Lymph Node Metastasis as a Prognostic Factor in Stage I-III Colon Cancer: An Observational Cohort Study.

Purpose: This study aimed to evaluate the prognostic impact of vascular invasion (VI) in comparison with that of lymph node metastasis (LNM) in non-metastatic colon cancer.Methods: Patients who underwent curative surgery for stage I-III colon cancer were divided into four groups depending on the status of VI and LNM (Group I: VI-/LNM-; Group II: VI+/LNM-; Group III: VI-/LNM+; Group IV: VI+/LNM+). Group III was subdivided according to the nodal (N) stage (Group IIIA: VI-/N1; Group IIIB: VI-/N2). Oncological outcomes were compared between Groups II and III.Results: In total, 793 non-metastatic colon cancer patients were included. Group II [hazard ratio (HR) 2.34, 1.01–5.41] and Group III (HR 1.91, 1.26–2.89) were independently associated with poor disease-free survival (DFS). The 5-year DFS rates were comparable in Groups II (71.6%) and III (72.5%) (P = 0.637). When Group III was subdivided into Groups IIIA and IIIB, DFS deteriorated in the following order: Groups IIIA, II, and IIIB. The 5-year DFS rates were 79.7, 71.6, and 61.4% in Groups IIIA, II, and IIIB, respectively. Group II had a tendency toward early recurrence. The 1- and 2-year DFS rates were 76.3 and 71.6% in Group II and 88.3 and 79.8% in Group III, respectively (P = 0.067 and 0.247). All recurrences in Group II were distant metastases.Conclusion: VI is a prognostic factor as significant as LNM and may be a stronger prognostic factor than N1 stage in non-metastatic colon cancer. Furthermore, a potential association was observed between VI and recurrence patterns, such as early recurrence and distant metastasis.

Neoadjuvant and adjuvant therapy of resectable colon cancer - Current standards and developments

The present review focusses on perioperative diagnosis and treatment of resectable colon cancer. In UICC stages associated with a higher risk of recurrence, adjuvant chemotherapy after resection of the primary tumor is an established standard. While initial data also indicate the benefit of Neoadjuvant, pre-operative chemotherapy, a final evaluation is still pending. The main focus of molecular testing in the perioperative setting is the analysis of microsatellite instability, which should routinely be performed in defined subgroups. In UICC stage II without risk factors, adjuvant therapy has a limited benefit and therefore is not a preferred option. In UICC stage II with risk factors, adjuvant therapy can be performed. The approach here is based on the recommendations applicable to stage III. In UICC stage III with low risk, adjuvant chemotherapy with CAPOX for 3months is preferentially recommended. In UICC stage III with high risk, adjuvant chemotherapy over 6 months is recommended, preferentially with FOLFOX. Microsatellite instability (MSI) is clearly associated with favorable prognosis in non-metastatic colon cancer. However, it cannot be considered a predictive factor for the efficacy of adjuvant chemotherapy. Specifically, recent data of the IDEA study have opened the arena for shared decision making between physicians and patients allowing to define individual treatment approaches based on common assessment of risks and benefits. After completion of perioperative treatment, structured follow-up is of great importance and should be carried out according to the recommendations of the S3 guideline.

Sarcopenia and Operative Outcomes for Non-metastatic Colon Cancer

Sarcopenia and Operative Outcomes for Non-metastatic Colon Cancer

Association of rurality and race with surgical treatment and outcomes for nonmetastatic colon cancer.

78 Background: Rural cancer patients face limited access to care due to greater travel distance and lack of specialty cancer care. Little is known about the intersection of rurality with well-documented racial disparities in colon cancer treatment and outcomes. Methods: We used fee-for-service Medicare claims to study patients age 65+ diagnosed with incident colon cancer without evidence of metastases who underwent cancer-directed surgery between 04/01/2016 and 09/30/2018. The primary exposure wasrurality of patient’s residence categorized as metropolitan (metro), micropolitan, and small town/rural. Outcomes were non-elective surgery (emergency department visit or transfer within 2 days prior to surgery), receipt of minimally invasive surgery (laparoscopic or robotic), 90-day surgical complications, and 90-day mortality. Logistic regression adjusted for patient demographics, cancer side (right vs left), comorbidities, and Area Deprivation Index. We assessed effect modification by race/ethnicity. Results: Of 57,710 patients with incident non-metastatic colon cancer, 37,691 (65%) underwent surgery. In this surgical cohort, small town/rural and micropolitan residents were more likely to be older, white, and Medicare-Medicaid dual-eligible than metro residents. After risk adjustment, patients in small town/rural areas had higher odds of non-elective surgery (OR =1.24, 95% CI:1.13-1.36) and lower odds of minimally invasive surgery (OR = 0.75, 95% CI:0.71-0.80) than patients living in metro areas. Similar results were seen for micropolitan areas. White rural patients had lower mortality than white urban patients, whereas black rural patients had higher mortality than black metro patients (see Table). Increasing area deprivation was associated with higher odds of non-elective surgery, surgical complications and mortality, and lower odds of minimally invasive surgery, even after adjusting for race and rurality. Conclusions: Small town/rural-residing Medicare beneficiaries undergoing surgery for non-metastatic colon cancer were less likely to receive optimal surgical management and had worse outcomes, especially among non-white patients. The compounded effect of rurality, race/ethnicity, and social deprivation should be incorporated in developing policies and interventions to improve care for rural cancer patients.[Table: see text]

Virtual Screening for Biomimetic Anti-Cancer Peptides from Cordyceps militaris Putative Pepsinized Peptidome and Validation on Colon Cancer Cell Line.

Colorectal cancer is one of the leading causes of cancer-related death in Thailand and many other countries. The standard practice for curing this cancer is surgery with an adjuvant chemotherapy treatment. However, the unfavorable side effects of chemotherapeutic drugs are undeniable. Recently, protein hydrolysates and anticancer peptides have become popular alternative options for colon cancer treatment. Therefore, we aimed to screen and select the anticancer peptide candidates from the in silico pepsin hydrolysate of a Cordyceps militaris (CM) proteome using machine-learning-based prediction servers for anticancer prediction, i.e., AntiCP, iACP, and MLACP. The selected CM-anticancer peptide candidates could be an alternative treatment or co-treatment agent for colorectal cancer, reducing the use of chemotherapeutic drugs. To ensure the anticancer properties, an in vitro assay was performed with “CM-biomimetic peptides” on the non-metastatic colon cancer cell line (HT-29). According to the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay results from peptide candidate treatments at 0–400 µM, the IC50 doses of the CM-biomimetic peptide with no toxic and cancer-cell-penetrating ability, original C. militaris biomimetic peptide (C-ori), against the HT-29 cell line were 114.9 µM at 72 hours. The effects of C-ori compared to the doxorubicin, a conventional chemotherapeutic drug for colon cancer treatment, and the combination effects of both the CM-anticancer peptide and doxorubicin were observed. The results showed that C-ori increased the overall efficiency in the combination treatment with doxorubicin. According to the acridine orange/propidium iodine (AO/PI) staining assay, C-ori can induce apoptosis in HT-29 cells significantly, confirmed by chromatin condensation, membrane blebbing, apoptotic bodies, and late apoptosis which were observed under a fluorescence microscope.

Outcomes of Non-metastatic Colon Cancer: A Single-Center Experience.

BackgroundColorectal cancer (CRC) is the most common gastrointestinal cancer. In the Saudi Cancer Registry, CRC ranked as the most common cancer in men and the third most common cancer in women. Data regarding the stage of CRC at presentation and patient demographics and outcomes in Saudi Arabia are lacking. This study aimed to investigate the prevalence, survival, and mortality rates of patients with non-metastatic CRC in a tertiary care hospital in Saudi Arabia. MethodsWe conducted a retrospective chart review of patients diagnosed with adenocarcinoma of the colon or rectum at King Abdulaziz University Hospital between 2013 and 2017. Patients aged ≥18 years who presented with non-metastatic CRC and underwent curative resection were included. Patients with rectal cancer or metastatic colon cancer were excluded. Data on demographic characteristics, histopathological findings, tumor-node-metastasis stage, biomarkers, and surgical interventions were collected. Recurrence-free survival was defined as the time from surgery to the date of recurrence or death. All statistical analyses were performed using Stata/IC 15.1 (StataCorp, College Station, TX, USA).ResultsAmong 260 patients diagnosed with CRC, 82 were included based on the inclusion/exclusion criteria. Among those patients, 65.9% were men and 47.5% were Saudi citizens. The mean age at the time of diagnosis was 60.8 years. Fifty-three patients (64.6%) had left-sided colon cancer. The mean tumor diameter was 52.6 mm. Most colon tumors were T3 lesions (71.3%), and 41% of patients did not have lymph node involvement (N0). Most patients (85.1%) underwent open surgery. In the multivariate analysis, only resection margin status and N stage (hazard ratio: 17.7 and 3.7, respectively) were identified as statistically significant factors affecting the recurrence-free survival. The one-, two-, and five-year recurrence-free rates were 80.5%, 66.5%, and 57.1%, respectively, and the one-, two-, and five-year and overall survival rates were 90.3%, 82.5%, and 82.5%, respectively.ConclusionsWe showed significant reductions in recurrence-free and overall survival within the first two years after surgical resection. Further prospective studies are needed to explore predictors.

Body Composition, Inflammation, and 5-Year Outcomes in Colon Cancer

Obesity, particularly visceral obesity and sarcopenia, are poor prognostic indicators in colon cancer. To explore the association between body composition profiles and 5-year colon cancer outcomes and delineate the associated underlying inflammatory processes. This multicenter translational cohort study included patients with nonmetastatic colon cancer who did not have underlying chronic inflammatory disorders and were not receiving anti-inflammatory drugs referred to tertiary cancer centers from 2009 to 2015. Preoperative acute phase proteins (white cell count, C-reactive protein, and albumin), cytokines (interleukin [IL]-1b, IL-2, IL-6, IL-10, interferon γ, and tumor necrosis factor α), vascular endothelial growth factor (VEGF), and cell surface receptor expression levels (CD11b and CD14) were measured. All patients underwent follow-up for at least 5 years. Data were analyzed in December 2020. Nonmetastatic colon cancer. The associations of body composition profiles with 5-year cancer recurrence and disease-specific mortality were analyzed using Mantel Cox log-rank test and Kaplan-Meier curves. A total of 28 patients were included (median [interquartile range] age, 67 [58-72] years; 22 [78.6%] men). Low skeletal muscle area (SMA) and high visceral to total fat ratio were associated with poor clinical and oncological outcomes, including increased 5-year recurrence (low SMA: hazard ratio [HR], 2.30 [95% CI, 1.41-2.89]; P = .04; high visceral to total fat ratio: HR, 5.78 [95% CI, 3.66-7.95]; P = .02). High visceral to total fat ratio was associated with increased 5-year disease-specific mortality (HR, 5.92 [95% CI, 4.04-8.00]; P = .02). Patients with low SMA who developed a cancer recurrence, compared with those who did not, had higher C-reactive protein (mean [SD], 31.24 [6.95] mg/dL vs 8.11 [0.58] mg/dL; P = .003), IL-6 (mean [SD], 1.93 [1.16] ng/mL vs 0.88 [0.14] ng/mL; P = .004), VEGF (mean [SD], 310.03 [122.66] ng/mL vs 176.12 [22.94] ng/mL; P = .007), and CD14 (mean [SD], 521.23 [302.02] ng/mL vs 322.07 [98.35] ng/mL; P = .03) expression and lower albumin (mean [SD], 3.8 [0.6] g/dL vs 43.50 [3.69] g/dL; P = .01), IL-2 (mean [SD], 0.45 [0.25] ng/mL vs 0.94 [0.43] ng/mL; P < .001), IL-10 (mean [SD], 8.15 [1.09] ng/mL vs 16.32 [4.43] ng/mL; P = .004), and interferon γ (mean [SD], 2.61 [1.36] ng/mL vs 14.87 [3.43] ng/mL; P = .02) levels. Patients with high visceral to total fat ratio who developed recurrence had higher levels of IL-6 (mean [SD], 5.26 [7.05] ng/mL vs 2.76 [3.11] ng/mL; P = .03) and tumor necrosis factor α (mean [SD], 5.74 [4.53] ng/mL vs 4.50 [1.99] ng/mL; P = .03). These findings suggest that low SMA and high visceral to total fat ratio were associated with worse colon cancer outcomes and with increased expression of proinflammatory cytokines and VEGF and inhibition of anti-inflammatory cytokines.

Stage dependent recurrence patterns and post-recurrence outcomes in non-metastatic colon cancer

Background Multiple meta-analyses have demonstrated that routine surveillance following colorectal cancer surgery improves survival outcomes. There is limited data on how recurrence patterns and post-recurrence outcomes vary by individual tumor stage. Methods Using a multi-site community cohort study, we examined the potential impact of primary tumor stage on the sites of recurrence, management of recurrent disease with curative intent, and post-resection survival. We also explored changes over time. Results Of 4257 new colon cancers diagnosed 2001 through 2016, 789 (21.1%) had stage I, 1584 (42.4%) had stage II, and 1360 (36.4%) had stage III colon cancer. For consecutive 5-year periods (2001–2005, 2006–2010, 2011–2016), recurrence rates have declined (23.4 vs. 17.1 vs. 13.6%, p < 0.001), however, the resection rates of metastatic disease (29.3 vs. 38.6 vs. 35.0%, p = 0.21) and post-resection 5-year survival (52.0 vs. 51.8 vs. 64.2%, p = 0.12) have remained steady. Primary tumor stage impacted recurrence rate (3.8 vs. 12 vs. 28%, p < 0.0001 for stage 1, 2, and 3), patterns of recurrence, resection of metastatic disease, (50 vs. 42 vs. 30%, p < 0.0001) and post-resection 5-year survival (92 vs. 64 vs. 44%, p < 0.001). Conclusion In this community cohort we defined significant differences in recurrence patterns and post-resection survival by tumor stage, with a diminishing rate of recurrence over time. While recurrence rates were lower with stage I and II disease, the high rate of metastatic disease resection and excellent post-resection outcomes help to justify routine surveillance in these patients.

ID: 3521919 IMPACT OF GROSS TUMOR MORPHOLOGY ON THE CLINICAL OUTCOMES OF NON-METASTATIC COLON CANCER : MULTICENTER RETROSPECTIVE COHORT STUDY

Background/Aims: There has been no data regarding the association between gross morphology and clinical outcomes of colon cancers. We aimed to investigate the relationship between endoscopic features and outcomes of non-metastatic colon cancer.

Hospitalizations among early-stage colon cancer patients receiving adjuvant chemotherapy: a real-world study.

ObjectiveTo assess the patterns of hospitalizations among early-stage colon cancer patients receiving adjuvant chemotherapy and to identify high-risk groups that may benefit from more careful monitoring in a real-world, population-based context.MethodsThis is a population-based study using linked administrative databases from the province of Alberta, Canada. Any events of hospitalization among patients with non-metastatic colon cancer undergoing upfront surgery followed by adjuvant chemotherapy were reviewed. Multivariable logistic regression analysis was used to examine factors associated with risk of hospitalization, and the impact of hospitalization on overall survival was assessed through Kaplan–Meier estimates and Multivariable Cox regression analysis.ResultsA total of 2257 patients were considered eligible and were included in the current analysis, including 483 patients (21.4%) who were hospitalized within 6 months of the start of adjuvant chemotherapy, and 1774 patients (78.6%) who were not. The following factors were associated with a higher hospitalization risk: older age (OR: 1.02; 95% CI 1.01–1.03), higher comorbidity (OR: 1.48; 95% CI 1.31–1.67), women (OR for men versus women: 0.79; 95% CI 0.64–0.98), living in the North zone (OR for Edmonton zone versus North zone: 0.60; 95% CI 0.42–0.87), and CAPOX chemotherapy (OR for CAPOX versus FOLFOX: 1.50; 95% CI 1.12–2.00). Patients with a history of hospitalization during adjuvant chemotherapy had a worse overall survival compared to patients who were not hospitalized (P < 0.001).ConclusionIn this study, one out of five colon cancer patients were hospitalized during adjuvant chemotherapy. Older individuals, women, those with higher comorbidity, and those receiving adjuvant CAPOX were more likely to be hospitalized.Supplementary informationThe online version contains supplementary material available at 10.1007/s00384-021-03952-4.