Non-metastatic Colon Cancer Patients Research Articles

FP4.1 - Impact of adjuvant chemotherapy on the 5 Year Overall Survival for non-metastatic colon cancer patients in Bulgaria - a population wide based observational study

Abstract Aim Colon cancer patients who receive adjuvant chemotherapy later in life have lower survival rates. NCCN guidelines recommend the use of adjuvant chemotherapy for patients with non-metastatic colon cancer. Our study's objective was to examine how adjuvant chemotherapy affected the 5-year overall survival (OS) of patients diagnosed with non-metastatic colon cancer in Bulgaria. Methodology This is a retrospective population-wide observational analysis of 8968 cases that was reported as colorectal cancer (CRC) in the Bulgarian National Cancer Registry (BNCR) from 2015 to 2016. The mean and median ages of patients with right colon (RCC) and left colon (LCC) were examined. An analysis was conducted to determine the effect of adjuvant chemotherapy on the 5-year overall survival for non-metastatic colon cancer. To estimate the statistical significance, chi-squared tests, ANOVA, and the Kaplan-Meier curve with log rank were employed. Results In comparison to LCC, RCC had a higher mean age at diagnosis of 68.9 versus 67.41 (p-Value=<0.001). For RCC and LCC, the corresponding median ages at diagnosis were 69 and 68. The 5-year OS for patients with non-metastatic colon cancer who received adjuvant chemotherapy was higher than for patients who did not (67.8% vs. 59%, respectively, p-Value=0.007), according to our study. Adjuvant chemotherapy was given to slightly more than 30% of patients. Conclusion The 5-Year OS for patients with non-metastatic colon cancer is improved by adjuvant chemotherapy, and Bulgaria should follow NCCN guidelines. The implementation of a systematic screening program can be advantageous for Bulgaria as well.

Lymph Node Metastases and Associated Recurrence-Free Survival in Microsatellite Stable and Unstable Colon Cancer.

In contrast to microsatellite stable (MSS) colon cancer, predictors of lymph node metastases and their association with recurrence are not well-defined in microsatellite instability (MSI) colon cancer. A cohort of nonmetastatic colon cancer patients undergoing surgery between 2015 and 2021 were evaluated for predictors of lymph node metastases (LNMs) and their association with recurrence-free survival (RFS). Of 1466 patients included in the analyses, 361 (25 %) had MSI. Compared with MSS, MSI was associated with earlier stage, fewer LNMs in the patients with N1 or N2 disease, and fewer high-risk features. Compared with the T3-T4 MSS patients, the odds ratios for LNM were 0.52 (95% confidence interval [CI], 0.38-0.71) for the T3-T4 MSI patients, 0.27 (95% CI, 0.38-0.71) for the T1-T2 MSS patients, and 0.15 (95 % CI, 0.08-0.26) for the T1-T2 MSI patients. In both groups, LNMs were associated with T category, patient age, and venous, lymphatic, or perineural invasion. In the MSS patients, LNMs were additionally associated with patient sex and histologic grade. Compared with the MSS patients, the MSI patients with N0 and N1 disease had a better 3-year RFS. However, the MSI patients with N2 disease had a lower rate of 3-year RFS than the MSS patients (hazard ratio, 19.75 vs 4.49). In MSI colon cancer, LNMs are 50 % less prevalent, but the factors associated withLNM are like those in MSS colon cancer. The improved prognosis traditionally associated with early-stage MSI colon cancers dissipates with four or more LNMs. These findings should be taken into consideration by clinicians selecting the most appropriate course of treatment for MSI colon cancer.

Achieving a Textbook Outcome in Colon Cancer Surgery Is Associated with Improved Long-Term Survival

Colon cancer surgery is a complex clinical pathway and traditional quality metrics may exhibit significant variability between hospitals and healthcare providers. The Textbook Outcome (TO) is a composite quality marker capturing the fraction of patients, in whom all desired short-term outcomes of care are realised. The aim of the present study was to assess the TO in a series of non-metastatic colon cancer patients treated with curative intent, with emphasis on long-term survival. Stage I-III colon cancer patients, who underwent curative colectomy following the Complete Mesocolic Excision principles, were retrospectively identified from the institutional database. TO was defined as (i) hospital survival, (ii) radical resection, (iii) no major complications, (iv) no reintervention, (v) no unplanned stoma and (vi) no prolonged hospital stay or readmission. In total, 128 patients (male 61%, female 39%, mean age 70.7 ± 11.4 years) were included in the final analysis. Overall, 60.2% achieved a TO. The highest rates were observed for "hospital survival" and "no unplanned stoma" (96.9% and 97.7%), while the lowest rates were for "no major complications" and "no prolonged hospital stay" (69.5% and 75%). Older age, left-sided resections and pT4 tumours were factors limiting the chances of a TO. The 5-year overall and 5-year cancer-specific survival were significantly better in the TO versus non-TO subgroup (81% vs. 59%, p = 0.009, and 86% vs. 65%, p = 0.02, respectively). Outcomes in colon cancer surgery may be affected by patient-, doctor- and hospital-related factors. TO represents those patients who achieve the optimal perioperative results, and is furthermore associated with improved long-term cancer survival.

Impact of diabetes and metformin use on recurrence and outcome in stage II–III colon cancer patients—A pooled analysis of three adjuvant trials

BackgroundDiabetes mellitus (DM) has been associated with increased colorectal cancer (CRC) risk and worse prognosis in metastatic CRC patients. In this large, pooled analysis of non-metastatic colon cancer (CC) patients, we investigated the impact of DM and metformin treatment on recurrence and survival. Patients and methodsA patient-level pooled analysis from three randomised adjuvant trials was performed. All patients had resection with curative intent of stage II or III CC and were treated with standard adjuvant fluoropyrimidine and oxaliplatin (±cetuximab). We investigated the impact of DM and metformin treatment on time to recurrence (TTR) and overall survival (OS). ResultsOf 5922 CC patients who had a median follow-up of 6.8 years, 621 patients (10.5%) had DM at CC diagnosis. Of those with DM, 327 patients (52.7%) were defined as metformin users and 294 patients (47.3%) as non-metformin users. CC patients with DM had a significantly shorter TTR (adjHR: 1.21; 95% CI, 1.03–1.42; p = 0.017) and OS (adjHR: 1.29; 95% CI, 1.09–1.52; p = 0.003) compared to non-diabetic CC patients. Diabetic CC patients not receiving metformin had a significantly worse TTR (adjHR: 1.28; 95% CI, 1.02–1.60; p = 0.032) and OS (adjHR: 1.41; 95% CI, 1.13–1.77; p = 0.003) as compared to non-diabetic patients. These worse outcomes were not significant in metformin users (TTR: adjHR: 1.16; 95% CI, 0.94–1.43; p = 0.168; OS: adjHR: 1.19; 95% CI, 0.95–1.48, p = 0.127). ConclusionsCC patients with DM had not only a significantly worse survival but also TTR. Furthermore, our data suggest that metformin may attenuate the detrimental effect of DM on CC patient outcomes.

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.

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.

VEGFR2 expressions in Th1 and CD8+ cytotoxic T lymphocytes (CTL) in colon cancer patients.

e15535 Background: VEGF receptors have an important role for inhibiting adaptive immun response in colon cancer. Therefore, we analyzed VEGF receptors in circulating T cell subsets according to stage in colon cancer patients. Methods: The prospective study group consisted of 50 patients with histologically confirmed colon cancer and 30 person without any cancer history as a control group. Peripheral blood specimens were collected from the patients after the diagnosis before inducing chemotherapy and radiotherapy. Patients with active infections or autoimmune disorders, who were treated with steroids and antibiotics in the last four weeks before the study enrollment were excluded from the study group. VEGFR2 expressions in circulating T cell subsets (Th1, Th2, Th17, CTL) were analyzed by flow cyctometry. Results: Age and gender were not different between the all study groups. Mean circulating CD4+ folicullar cells were less in colon cancer patients (9.54%±3.99) than the control group (12.03%±4.34), (p &lt; 0.01). Mean circulating CD8+ follicular cells were higher in metastatic colon cancer (n = 26) 2.48% ± 1.68, than the non-metastatic colon cancer patients (n = 24) 1.63% ± 1.37, (p = 0.02). Mean VEGFR2 expressions in Th1 cells were higher in colon cancer patients 248.8 (Mean Flourescein intensity-MFI) than the control group 224.6, (P = 0.006). Mean VEGFR2 expressions in CTL were higher in colon cancer patients (381.8) than the control group (284.7), (p &lt; 0.001). PD-1 expressions were not different between the colon cancer patients and the control group in all circulating T cell subsets. Mean VEGFR2 expressions in Th17 cells were higher non-metastatic colon cancer patients than the metastatic colon cancer patients (326.5 and 268.4 MFI, respectively, p = 0.02). Conclusions: VEGFR2 expressions are increased in circulating Th1 and CTL subsets in colon cancer patients. Whereas PD-1 expressions were not different in circulating T cell subsets than the control. VEGFRs may play an important role for the inhibition of circulating T cell subsets in colon cancer.

Recruitment strategies and design considerations in a trial of resistance training to prevent dose-limiting toxicities in colon cancer patients undergoing chemotherapy

Low muscle is associated with an increased risk of chemotherapy-related dose limiting toxicities (DLT) in cancer patients. Resistance training (RT) improves muscle mass; however, the effects of RT on preventing DLTs and dose reductions in colon cancer patients has not been investigated.FOcus on Reducing dose-limiting toxicities in Colon cancer with resistance Exercise (FORCE) is a multicenter, randomized clinical trial examining the effects of RT on relative dose intensity (RDI; primary outcome) and moderate and severe chemotoxicities (primary outcome) in non-metastatic colon cancer patients receiving adjuvant chemotherapy. Patients (N = 180) will be recruited from Kaiser Permanente Northern California, Dana-Farber Cancer Institute, and Penn State Cancer Institute. This paper describes recruitment strategies and design considerations.Patients will be randomized in equal numbers to RT intervention or control. Patients have baseline and post completion of chemotherapy visits where information on anthropometry, physical function, body composition, quality of life, physical activity and dietary behaviors, and inflammatory blood markers will be collected. Patient-reported outcomes of chemotherapy side effects will be collected around the time of chemotherapy throughout the duration of the trial. Intervention participants will be prescribed a progressive RT program consisting of 4–6 visits with a certified exercise trainer, delivered either in-person or remotely by video conference, and will be asked to engage twice weekly in-home training sessions. Control patients at the end of the study receive a consult with a FORCE exercise trainer, an online exercise RT training program and a set of resistance bands.Results of this trial will provide information on the benefit of resistance exercise as a treatment to increase RDI.

Early-onset colorectal cancer in younger patients: A population-based study.

124 Background: In the US, the incidence of colorectal cancer (CRC) is increasing in patients younger than 50 years who may present with advanced stage, high grade, left-sided colon or rectal cancers with signet ring cell histopathology, aggressive clinical course, and reduced overall survival. Understanding the characteristics of this population could inform screening, early detection, and optimal treatment. In this study, we describe the attributes of adults who are 50 years and younger with a first diagnosis of CRC and ascertain molecular testing rates and time to surgery by using data from a commercially insured cohort in the U.S. Methods: This retrospective study of patients ages 50 and younger with a first diagnosis of CRC utilizes the IBM MarketScan database, and focuses on claims from January 2013 to December 2018. Included patients had continuous insurance enrollment of 12 months before and 6 months after diagnosis. We determined rates of tumor testing for microsatellite instability (MSI) or immunohistochemistry (IHC) for mismatch repair (MMR) proteins and referral to genetic services in all patients, as well as mutational analysis of KRAS, NRAS, and BRAF in metastatic CRC patients. Time to surgical resection of primary tumor (TTS) in non-metastatic colon cancer patients was measured. Results: During the 5-year period, 10,577 patients ages 18 to 50 years had a first diagnosis of CRC, which was 15.6% of the 67,921 adults of all ages with CRC. Claims for MSI or IHC for MMR proteins within 120 days of initial diagnosis were done in 4,429 (41.9%) patients and referral to genetics services/counseling within 1 year of initial diagnosis were done in 443 (4.1%) patients. Among metastatic CRC patients, KRAS, NRAS, or BRAF tumor mutational analyses within 120 days of initial diagnosis were documented in 323 (31.5%). The median TTS ranged from 7 to 15 days with no statistically significant differences based on geographic region or health insurance plan type. Conclusions: Younger patients with early onset CRC had low rates of referral to genetics services, tumor MSI or IHC for MMR proteins testing, and KRAS, NRAS, and BRAF mutational analysis. There were no geographic or insurance type trends in TTS in non-metastatic colon cancer patients. Although underreporting is possible in our study, the findings of low utilization of genetic services and tumor genomic testing in these younger patients with early onset CRC should alert the oncology community to critical management gaps in the care of this population.

Novel Nomograms Individually Predicting Overall Survival of Non-metastatic Colon Cancer Patients.

Background: This study aimed to develop an effective prognostic nomogram for predicting non-metastatic colon cancer.Methods: The Surveillance, Epidemiology, and End Results program was utilized to analyze patients who underwent surgical therapy (25,350 for training, 10,860 for validation). Nomograms were created depending upon multivariate analysis in the training cohort and were compared to current American Joint Committee on Cancer (AJCC) classifications. Areas under the receiver-operating characteristic curves (AUCs), Akaike's information criterions (AICs), and calibration curves were used. The clinical benefit was measured using decision curve analyses (DCAs). The validation cohort was used to validate the results.Results: Nomogram 1 included age, gender, histological grade, T stage, number of retrieved lymph nodes, tumor size, and N stage. Nomogram 2 included age, gender, histological grade, T stage, number of retrieved lymph nodes, tumor size, and number of positive lymph nodes. The prognostic discrimination of nomogram 1 (AUC, 0.729, 95% CI, 0.723–0.736) was better than that of nomogram 2 (AUC, 0.704, 95% CI, 0.698–0.710, p < 0.001) in five-year overall survival in the training cohort. Nomogram 1 (AIC, 137,319) also showed superior model-fitting compared to nomogram 2 (AIC, 137,453). Similarity, nomogram 1 was better than the AJCC 6th and 8th TNM classifications. DCA revealed that nomogram 1 had a superior net benefit than other models. These findings were validated using the validation cohort.Conclusions: The proposed nomogram 1 was a better prognostic prediction model with better discrimination and superior model-fitting for patients with non-metastatic colon cancer, which might prove to be clinically helpful.

Nomogram for predicting survival of non-metastatic colon cancer patients

Nomogram for predicting survival of non-metastatic colon cancer patients

Outcomes of non-metastatic colon cancer patients in relationship to socioeconomic status: an analysis of SEER census tract-level socioeconomic database.

To evaluate the outcomes of non-metastatic colon cancer patients in relation to the socioeconomic status (SES) at diagnosis based on the Surveillance, Epidemiology, and End Results (SEER) census tract level-SES database. SEER SES census tract level database represents a specially designed database to integrate different aspects of SES among cancer patients. It reports a composite SES index for each patient. Patients were then stratified into three SES groups. Patients with a non-metastatic colon cancer diagnosis, diagnosed (2004-2015), and who were included in this specialized database were included in the current study. Multivariate Cox regression analysis was used to assess the impact of SES index on colon cancer-specific survival. A total of 80,121 patients with non-metastatic colon cancer were included in the current study. Comparing patients in the lower SES group with patients in the higher SES group, patients with lower SES were more likely to have a younger age at presentation (P < 0.001), black race (P < 0.001) and more advanced stage at presentation (P < 0.001). The impact of the SES on colon cancer-specific survival was evaluated through multivariate Cox regression analysis adjusted for age, sex, race, stage, and colon cancer side. Lower SES was associated with worse colon cancer-specific survival (hazard ratio for group 1 versus group 3: 1.257; 1.190-1.328; P < 0.001). Interaction testing between race (black race versus white race) and SES was non-significant (P = 0.932). Lower SES is associated with worse colon cancer-specific survival among non-metastatic colon cancer patients.

LONG TERM opioid use in RURAL NON-metastatic colon cancer patients.

e15174 Background: Cancer related pain and subsequent long-term opioid (LTO) use worsens the opioid epidemic and facilitates abuse. Non-metastatic colon cancer (CC) is a potentially curable malignancy and prescription opioid (PO) may increase risks of adverse events when CC has been eradicated. Methods: A retrospective study evaluated stage I-III CC patients between January 2013 and January 2018 across rural cancer clinics in New Mexico who received PO during their cancer diagnosis and treatment. It excluded patients with stage IV CC, concurrent malignancies and non-cancer pain. Descriptive statistics, Chi-square and logistic regression were performed to identify correlation and predictors of LTO use. Results: Among 197 patients identified, opioids were prescribed in 24% (48/197); 22 patients met inclusion criteria. Mean age was 65.1±9.8 years; 68% male; Stage I (4.5%), II (36.3%), III (59.1%). Adjuvant chemotherapy was given in 91% (20/22). Oxaliplatin regimen was used in 63.6% (14/22). One year after therapy, 27.3% (6/22) still had neuropathy. The rate of opioid use was 72.7% (16/22) at 3 months, 54.5% (12/22) at 6 months and 41% (9/22) at 12 months; 56.2% (9/16) of opioid users at 3 months were also using opioids at 12 months from initial prescription (X2 5.71 p = 0.046). Also, 75% (9/12) of opioid users at 6 months, continued using opioids at 12 months (X2 12.7 p = 0.0001). Patients with smoking history, unemployed and PO from a surgeon, were more likely to be LTO users at 12 months; however, it was not statistically significant. Conclusions: Non-metastatic CC patients who continue to use opioids at 3 months are at a significantly higher risk of LTO use at one year. Biological and social factors in rural communities can be important determinants of this use pattern. The challenges surrounding opioid use and the need for safe and effective alternative analgesics require urgent attention and regulatory discourse.

RandomiSed clinical trial assessing Use of an anti-inflammatoRy aGent in attenUating peri-operatiVe inflAmmatioN in non-meTastatic colon cancer \u2013 the S.U.R.G.U.V.A.N.T. trial

BackgroundPeri-operative inflammation has been extensively highlighted in cancer patients as detrimental. Treatment strategies to improve survival for cancer patients through targeting peri-operative inflammation have yet to be devised.MethodsWe conducted a multi-centre, randomised controlled clinical trial using Taurolidine in non-metastatic colon cancer patients. Patients were randomly assigned to receive Taurolidine or a placebo. The primary endpoint for the study was the mean difference in day 1 IL-6 levels. Secondary clinical endpoints included rates of post-operative infections and tumor recurrence.ResultsA total of 293 patients were screened for trial inclusion. Sixty patients were randomised. Twenty-eight patients were randomised to placebo and 32 patients to Taurolidine. IL-6 levels were equivalent on day 1 post-operatively in both groups. However, IL-6 levels were significantly attenuated over the 7 day study period in the Taurolidine group compared to placebo (p = 0.04). In addition, IL-6 levels were significantly lower at day 7 in the Taurolidine group (p = 0.04). There were 2 recurrences in the placebo group at 2 years and 1 in the Taurolidine group. The median time to recurrence was 19 months in the Placebo group and 38 months in the Taurolidine group (p = 0.27). Surgical site infection was reduced in the Taurolidine treated group (p = 0.09).ConclusionPeri-operative use of Taurolidine significantly attenuated circulating IL-6 levels in the initial 7 day post-operative period in a safe manner. Future studies are required to establish the impact of IL-6 attenuation on survival outcomes in colon cancer.Trial registrationThe trial was registered with EudraCT (year = 2008, registration number = 005570–12) and ISRCTN (year = 2008, registration number = 77,829,558).

Impact of primary tumor side on the outcomes of patients with non-metastatic colon cancer; a patient-level pooled analysis of two clinical trials

ABSTRACTObjective: To assess the impact of primary tumor side on the outcomes of non-metastatic colon cancer patients included in two clinical trials.Methods: Overall and disease-free survivals were assessed according to the side of the tumor, through Kaplan–Meier analysis. Univariate and Multivariate analysis of predictors of disease-free survival was performed through Cox regression analysis.Results: Kaplan–Meier analysis of disease-free survival according to the side of the primary tumor was conducted. In the overall cohort, the right-sided disease has longer disease-free survival compared to left-sided disease (p = 0.005). When the analysis was repeated among different treatment strata (observation, adjuvant 5FU/LCV, adjuvant edrecolomab), right-sided colon cancer has longer disease-free survival among observation-treated patients only (p = 0.020). Multivariate analysis was conducted among the three subsets of adjuvant treatment. The left side of the primary tumor was predictive of worse disease-free survival in patients treated with observation only (p = 0.005) but not in patients treated with adjuvant 5FU/LCV (p = 0.345) or patients treated with adjuvant edrecolomab (p = 0.661).Conclusion: Stage II right-sided colon cancer patients have better disease-free survival compared to stage II left-sided colon cancer patients when treated with surgery only. This survival difference disappears if patients were treated with adjuvant fluoropyrimidines.

Adherence to colonoscopy at 1 year following resection of localized colon cancer: a retrospective cohort study.

Background:For patients with stages I-III colon cancer who have undergone surgical resection, guidelines recommend surveillance colonoscopy at 1 year. However, limited data exist on adherence and associated factors. We aimed to determine the rate of adherence to surveillance colonoscopy at 1 year among nonmetastatic colon cancer patients who underwent resection and factors associated with adherence.Methods:In this population-based retrospective cohort study, the Surveillance, Epidemiology, and End Results (SEER)–Medicare database was used. We identified patients with stages I-III colon cancer who underwent surgical resection and survived >3 years without recurrence (no chemotherapy after 8 months) from 2002–2011. Our primary outcome was a colonoscopy claim 10–15 months after resection. We used multivariable regression analysis to assess associations between sociodemographic and clinical factors and receipt of timely colonoscopy.Results:Among 28,732 patients who survived >3 years without recurrence, 7967 (28%) did not undergo colonoscopy; 12,033 (42%) had it at one year, with 3159 (11%) before 10 months and 5573 (19%) after 15 months. Decreased adherence was associated with older age; being male versus female; being black or Hispanic versus white; higher tumor stage; left-sided tumors versus right sided; and increased comorbidities. Chemotherapy receipt was associated with increased adherence (odds ratio 2.06; 95% confidence interval 1.88–2.24).Conclusions:In a large population-based sample of individuals aged ⩾ 65 years, only 42% of colon cancer survivors underwent 1-year surveillance colonoscopy. Demographic and clinical factors were associated with adherence.

Expression of voltage-gated sodium channel Nav1.5 in non-metastatic colon cancer and its associations with estrogen receptor (ER)-\u03b2 expression and clinical outcomes

BackgroundVoltage-gated sodium channel 1.5 (Nav1.5) potentially promotes the migratory and invasive behaviors of colon cancer cells. Hitherto, the prognostic significance of Nav1.5 expression remains undetermined. The present study aimed to explore the associations of Nav1.5 expression with clinical outcomes and estrogen receptor-β (ER-β) expression in non-metastatic colon cancer patients receiving radical resection.MethodsA total of 269 consecutive patients with pathologically confirmed stages I–III colon cancer who underwent radical resection were selected. Nav1.5 and ER-β expression was detected by using immunohistochemistry (IHC) on tissue microarray constructed from paraffin-embedded specimens. IHC score was determined according to the percentage and intensity of positively stained cells. Statistical analysis was performed with the X-tile method, k coefficient, Chi square test or Fisher’s exact test, logistic regression, log-rank test, and Cox proportional hazards models.ResultsWe found that Nav1.5 was commonly expressed in tumor tissues with higher mean IHC score as compared with matched tumor-adjacent normal tissues (5.1 ± 3.5 vs. 3.5 ± 2.7, P < 0.001). The high expression of Nav1.5 in colon cancer tissues was associated with high preoperative carcinoembryonic antigen level [odds ratio (OR) = 2.980; 95% confidential interval (CI) 1.163–7.632; P = 0.023] and high ER-β expression (OR = 2.808; 95% CI 1.243–6.343; P = 0.013). Log-rank test results showed that high Nav1.5 expression contributed to a low 5-year disease-free survival (DFS) rate in colon cancer patients (77.2% vs. 92.1%, P = 0.048), especially in patients with high ER-β expression tumor (76.2% vs. 91.3%, P = 0.032). Analysis with Cox proportional hazards model demonstrated that high Nav1.5 expression [hazard ratio (HR) = 2.738; 95% CI 1.100–6.819; P = 0.030] and lymph node metastasis (HR = 2.633; 95% CI 1.632–4.248; P < 0.001) were prognostic factors for unfavorable DFS in colon cancer patients.ConclusionsHigh expression of Nav1.5 was associated with high expression of ER-β and indicated unfavorable oncologic prognosis in patients with non-metastatic colon cancer.

Plasma miR-122 and miR-200 family are prognostic markers in colorectal cancer.

Circulating microRNAs (miRNAs) have been proposed as minimally invasive prognostic markers for various types of cancers, including colorectal cancer (CRC), the third most diagnosed cancer worldwide. We aimed to evaluate the levels of circulating miRNAs that might serve as markers for CRC prognosis and survival. We included plasma samples of 543 CRC patients with stage I-IV disease from a population-based study carried out in Germany. After comprehensive evaluation of current literature, 95 miRNAs were selected and measured with Custom TaqMan® Array MicroRNA Cards. Plasma samples of non-metastatic and metastatic colon cancer patients, each group consisting of ten patients with 'good' and ten patients with 'bad' prognosis were screened. Identified candidate miRNAs were further validated by RT-qPCR in the whole study cohort. The association of the miRNA levels with patients' survival and the prognostic subtypes was analyzed with uni- and multivariate logistic regression and Cox proportional hazards regression models. Increased miR-122 levels were associated with a 'bad' prognostic subtype in metastatic CRC (Odds ratio: 1.563, 95% confidence interval (CI): 1.038-2.347) and a shorter relapse-free survival and overall survival for non-metastatic (Hazard ratio (HR): 1.370, 95% CI: 1.028-1.825; HR: 1.353, 95% CI: 1.002-1.828) and metastatic (HR: 1.264, 95% CI: 1.050-1.520; HR: 1.292, 95% CI: 1.078-1.548) CRC patients. Additionally, several members of the miR-200 family showed associations with patients' prognosis and correlations to clinicopathological characteristics. The here identified miRNA markers, miR-122 and the miR-200 family members, could be of use in the development of a multi-marker blood test for CRC prognosis.

Enhancement of the Immunostimulatory Functions of Ex Vivo–Generated Dendritic Cells from Early-Stage Colon Cancer Patients by Consecutive Exposure to Low Doses of Sequential-Kinetic-Activated IL-4 and IL-12. A Preliminary Study

Dendritic cells (DCs), specialized antigen-presenting cells bridging innate and adaptive immunity, play a crucial role in determining specific immune response to tumors. Because of their potent immunoregulatory capacities, DCs have been exploited in anticancer vaccination, with limited success thus far. This pilot study compared low-dose interleukin (IL)-4 and IL-12 prepared by sequential kinetic activation (SKA) with standard doses of the same recombinant human cytokines on functional activity of ex vivo–generated monocyte-derived (Mo) DCs from colon carcinoma patients and normal subjects. MoDCs were exposed to medium alone, SKA-IL-4 (0.5 fg/ml), or SKA-IL-12 (2 fg/ml), alone or consecutively combined, in parallel with rhIL-4 (50 ng/ml) and rhIL-12 (1 ng/ml). Primary allogeneic one-way mixed lymphocyte reaction (MLR) was the end point to assess in vitro T-lymphocyte proliferation in response to MoDCs, and secreted IL-12p70 and interferon-γ in MLR supernatants measured by ELISA to assay for T-helper 1–promoting MoDC phenotype. No single agent enhanced the compromised allostimulatory activity of MoDCs from colon cancer patients, unlike healthy donors. However, MoDCs from nonmetastatic colon cancer patients, after sequential exposure to SKA-IL-4 (48 hours) and SKA-IL-12 (24 hours), displayed increased T-cell stimulatory capacity by MLR and acquired driving T-helper 1 polarization activity, although less markedly than the effects induced by recombinant human cytokines or found in normal subjects. These results point to an immunomodulatory capacity of low-dose SKA-IL-4 and SKA-IL-12 and encourage further investigation to provide clues for the rational development of new and more effective immunotherapeutic strategies against cancer.