Chemotherapy For Colon Cancer Research Articles

Response Prediction after Neoadjuvant Chemotherapy for Colon Cancer Using CT Tumor Regression Grade: A Preliminary Study.

To investigate whether CT-based tumor regression grade (ctTRG) can be used to predict the response to neoadjuvant chemotherapy (NAC) in colon cancer. A total of 53 patients were enrolled. Two radiologists independently assessed the ctTRG using the length, thickness, layer pattern, and luminal and extraluminal appearance of the tumor. Changes in tumor volume were also analyzed using the 3D Slicer software. We evaluated the association between pathologic TRG (pTRG) and ctTRG. Patients with Rödel's TRG of 2, 3, or 4 were classified as responders. In terms of predicting responder and pathologic complete remission (pCR), receiver operating characteristic was compared between ctTRG and tumor volume change. There was a moderate correlation between ctTRG and pTRG (ρ = -0.540, p < 0.001), and the interobserver agreement was substantial (weighted κ = 0.672). In the prediction of responder, there was no significant difference between ctTRG and volumetry (Az = 0.749, criterion: ctTRG ≤ 3 for ctTRG, Az = 0.794, criterion: ≤ -27.1% for volume, p = 0.53). Moreover, there was no significant difference between the two methods in predicting pCR (p = 0.447). ctTRG might predict the response to NAC in colon cancer. The diagnostic performance of ctTRG was comparable to that of CT volumetry.

Effective combination of liposome-targeted chemotherapy and PD-L1 blockade of murine colon cancer.

Therapeutic cancer drug efficacy can be limited by insufficient tumor penetration, rapid clearance, systemic toxicity and (acquired) drug resistance. The poor therapeutic index due to inefficient drug penetration and rapid drug clearance and toxicity can be improved by using a liposomal platform. Drug resistance for instance against pemetrexed, can be reduced by combination with docetaxel. Here, we developed a specific liposomal formulation to simultaneously deliver docetaxel and pemetrexed to enhance efficacy and safety. Hydrophobic docetaxel and hydrophilic pemetrexed were co-encapsulated into pH-sensitive liposomes using a thin-film hydration method with high efficiency. The physicochemical properties, toxicity, and immunological effects of liposomes were examined in vitro. Biodistribution, anti-tumor efficacy, and systemic immune response were evaluated in vivo in combination with PD-L1 immune checkpoint therapy using two murine colon cancer models. In cellular experiments, the liposomes exhibited strong cytotoxicity and induced immunogenic cell death. In vivo, the treatment with the liposome-based drug combination inhibited tumor development and stimulated immune responses. Liposomal encapsulation significantly reduced systemic toxicity compared to the delivery of the free drug. Tumor control was strongly enhanced when combined with anti-PDL1 immunotherapy in immunocompetent mice carrying syngeneic MC38 or CT26 colon tumors. We showed that treatment with liposome-mediated chemotherapy of docetaxel and pemetrexed combined with anti-PD-L1 immunotherapy is a promising strategy for the treatment of colon cancers.

Benefits of Adjuvant Chemotherapy for Clinical T3-4N0 Rectal Cancer After Preoperative Chemoradiotherapy.

While the guidelines for adjuvant chemotherapy (AC) for colon cancer are relatively standardized, those for early rectal cancer are still lacking. We therefore evaluated the role of AC in clinical stage II rectal cancer treatment after preoperative chemoradiotherapy (CRT). Patients diagnosed with early rectal cancer (defined by clinical stage T3/4, N0) who completed CRT followed by surgery were enrolled in this retrospective study. To evaluate the role of AC, we analyzed the risk of recurrence and survival based on clinicopathologic parameters and adjuvant chemotherapy. Of the 112 patients, 11 patients (9.8%) experienced recurrence and five patients (4.8%) died. In a multivariate analysis, circumferential resection margin involvement (CRM+) on magnetic resonance imaging at diagnosis, CRM involvement following neoadjuvant therapy (ypCRM+), tumor regression grade (≤G1) and no-AC were considered poor prognostic factors for recurrence free survival (RFS). In addition, ypCRM+ and no-AC were associated with poor overall survival (OS) in the multivariate analysis. AC including 5-FU monotherapy demonstrated the benefits of reduced recurrence and prolonged survival in clinical stage II rectal cancer, even in pathologic stage following neoadjuvant therapy (ypStage) 0-I. Further prospective studies are needed to verify the benefit of each regimen of AC and the development of a method that can accurately predict CRM status before surgery, and a vigorous treatment that can induce CRM non-involvement (CRM-) should be considered even in early stages of rectal cancer.

Clinical Evidence for the Benefits of Neoadjuvant Chemotherapy and Immunotherapy in Colon Cancer: A Concise Review.

Neoadjuvant chemotherapy (NAC) has long been considered technically difficult in locally advanced colon cancer (LACC). However, the introduction of oxaliplatin-based regimens led to a growing interest in NAC for patients with LACC. Several cohort studies showed that NAC was safe and reduced the rate of incomplete resection in patients with LACC. This was followed by the pivotal phase III FOxTROT trials, which showed significant benefits of NAC in this population. However, in patients with deficient mismatch repair (dMMR), the response to a neoadjuvant fluoropyrimidine regimen may be poor, limiting the benefit of NAC in this subset of patients. Neoadjuvant immunotherapy is a potential alternative for NAC in LACC patients with dMMR. In this concise review, we present the published clinical evidence evaluating the efficacy and safety of NAC and/or neoadjuvant immunotherapy in patients with LACC. Overall, the evidence suggests that NAC can be associated with significant downstaging and tumor regression, which facilitate surgical resection. However, the impact of NAC on long-term survival is still under investigation. Despite the promising results of NAC in LACC, several concerns still exist that necessitate further evidence. On the other hand, LACC patients with dMMR can benefit from neoadjuvant immunotherapy; however, further trials are still needed to confirm its effectiveness, as well as biomarkers that can predict response.

Differences in Toxicity Between Ashkenazi and Sephardic Jews With Colon Cancer Treated With Adjuvant Chemotherapy: A Prospective Study.

Ethnicity of cancer patients is increasingly being recognized as an important factor that may influence intergroup variation in toxicity and efficacy of chemotherapy. Data from our institution suggested that differences in chemotherapy-associated toxicity are not limited to distanced ethnic subgroups, such as Caucasians, Afro-Americans, or Asians, but may exist even between two closely related Caucasian ethnic subgroups, such as Ashkenazi and Sephardic Jews. This study aimed to explore differences in severity and frequency of various side effects, including neurotoxicity between patients from the two Jewish subgroups receiving oxaliplatin-containing adjuvant chemotherapy for colon cancer (CC). We recruited 75 patients, with performance status 0-1 and no background of neuropathy between 2012 and 2016. All patients completed a neurotoxicity questionnaire (NQ) and a QoL questionnaire (QoLQ) at baseline and the NQ also at each treatment cycle; during follow up, patients filled out the NQ and the QoLQ every four months for a total of one year. Of the 75 participants, 66 were evaluable for the study including 34 (52%) Sephardic and 32 (48%) Ashkenazi Jews. Grade ≥2 vomiting and diarrhea occurred more often in Sephardic than in Ashkenazi patients (p=0.008 and 0.012, respectively). Of the 66 evaluable patients, 11 (17%) developed grade 3 neurotoxicity; of these, 9 were Sephardic and 2 were Ashkenazi (p=0.028). There were no significant differences in the dynamics of QoL between both subgroups. Sephardic patients receiving oxaliplatin-containing regimens are at an increased risk for neurotoxicity and other side effects as compared to their Ashkenazi counterparts.

Benefit of Uracil-Tegafur Used as a Postoperative Adjuvant Chemotherapy for Stage IIA Colon Cancer.

Background and Objectives: Postoperative adjuvant therapy with uracil and tegafur (UFT) is often used for stage II colon cancer in Japan, but a limited number of studies have investigated the effects of UFT in these patients. Materials and Methods: We conducted a population-based cohort study in patients with resected stage II colon cancer comparing the outcomes after postoperative adjuvant chemotherapy with UFT with an observation-only group. The data were collected from the Taiwan National Health Insurance Research Database from 2000 to 2015. The outcomes of the study were disease-free survival (DFS) and overall survival (OS). The hazard ratios (HRs) were calculated using multivariate Cox proportional hazard regression models. Results: No differences in the DFS and OS were detected between the UFT (1137 patients) and observation (2779 patients) cohorts (DFS: adjusted HR 0.702; 95% confidence interval (CI) 0.489-1.024; p = 0.074) (OS: adjusted HR 0.894; 95% CI 0.542-1.186; p = 0.477). In the subgroup analyses of the different substages, UFT prolonged DFS in patients with stage IIA colon cancer (adjusted HR 0.652; 95% CI 0.352-0.951; p = 0.001) compared with DFS in the observation cohort, but no differences in the OS were detected (adjusted HR 0.734; 95% CI 0.475-1.093; p = 0.503). Conclusions: Our results show that DFS improved significantly in patients with stage IIA colon cancer receiving UFT as a postoperative adjuvant chemotherapy compared with DFS in the observation group.

Assessment of Attitudes Toward Initiation of Immediate Adjuvant Chemotherapy for Colon Cancer

IntroductionEarly initiation of chemotherapy after surgery for colon cancer has survival benefits. Immediate adjuvant chemotherapy (IAC) involves giving chemotherapy during surgical resection and immediately postoperatively. This novel approach has been shown to be safe, eliminating delays in adjuvant treatment that could increase the risk of micro-metastatic spread. The aim of this study was to assess the willingness of the general public to accept IAC. Materials and methodsBetween March and April 2021, 800 telephone interviews were conducted with a sample of adult New York State residents. The Survey Research Institute of Cornell University conducted all surveys. Kruskal–Wallis, chi-squared, and Fisher’s tests were conducted using R 4.0.2. ResultsThree scenarios were presented: (1) receiving IAC resulting in improved survival and quality of life, (2) finishing chemotherapy earlier without survival impact, and (3) finishing chemotherapy earlier but with possible side effects. Respondents with higher education were more likely to accept (1) & (2), males were more likely to accept (2) & (3), higher income respondents were more likely to accept (1) & (3), and those with more work hours were more likely to accept (2). Lastly, 16% responded they would be very or extremely likely, and 52% respondents would be somewhat likely or likely to accept intraoperative chemotherapy, even if it may not be necessary. ConclusionsRespondents were likely to accept IAC if offered. Given the known risk of delayed adjuvant chemotherapy (AC) in colon cancer, further research is warranted to determine the survival and quality of life (QOL) benefits of IAC.

Targeted maximum likelihood estimation for causal inference in survival and competing risks analysis.

Targeted maximum likelihood estimation (TMLE) provides a general methodology for estimation of causal parameters in presence of high-dimensional nuisance parameters. Generally, TMLE consists of a two-step procedure that combines data-adaptive nuisance parameter estimation with semiparametric efficiency and rigorous statistical inference obtained via a targeted update step. In this paper, we demonstrate the practical applicability of TMLE based causal inference in survival and competing risks settings where event times are not confined to take place on a discrete and finite grid. We focus on estimation of causal effects of time-fixed treatment decisions on survival and absolute risk probabilities, considering different univariate and multidimensional parameters. Besides providing a general guidance to using TMLE for survival and competing risks analysis, we further describe how the previous work can be extended with the use of loss-based cross-validated estimation, also known as super learning, of the conditional hazards. We illustrate the usage of the considered methods using publicly available data from a trial on adjuvant chemotherapy for colon cancer. R software code to implement all considered algorithms and to reproduce all analyses is available in an accompanying online appendix on Github.

The influence of adjuvant chemotherapy dose intensity on overall survival in resected colon cancer: a multicentered retrospective analysis

BackgroundColorectal cancer remains the second leading cause of cancer death in North America. Fluorouracil and oxaliplatin based adjuvant chemotherapy for resected colon cancer (CC) reduces cancer recurrence, but also causes significant toxicity requiring dose reductions. The effect of dose intensity on survival outcomes is not fully understood and strengthening the evidence supports informed decision making between patients and oncologists.MethodsPatients treated with adjuvant chemotherapy, between 2006 and 2011, for resected colon cancer at four Canadian academic cancer centers were retrospectively analyzed. All patients must have received oxaliplatin with either capecitabine (CAPOX) or 5-FU (FOLFOX). Dose intensity (DI) was calculated as total delivered dose of an individual chemotherapy agent divided by the cumulative intended dose of that agent. The influence of DI on overall survival was examined.ResultsFive hundred thirty-one patients with high-risk stage II or stage III resected CC were eligible and included in the analysis. FOLFOX was the most common regimen (69.6%) with 29.7% of patients receiving CAPOX and 0.7% receiving both therapies. Median follow-up was 36.7 months. The median DI for 5-FU and capecitabine was 100% and 100% with 13.6% and 9.8% of patients receiving ≤ 80% DI, respectively. The median DI of oxaliplatin was 70% with 56.8% of patients receiving ≤ 80% DI. A DI of > 80% for each chemotherapy component was associated with a significant improvement in overall survival compared to those with a DI of ≤ 80% (5-FU HR = 0.23, 95% CI = 0.08–0.65, p = 0.006; capecitabine HR = 0.56, 95% CI = 0.33–0.94, p = 0.026; oxaliplatin HR = 0.52, 95% CI = 0.33–0.82, p = 0.005). Patients with T2 and/or N2 disease with an oxaliplatin DI > 80% had a trend towards improved survival (HR = 0.62, 95% CI = 0.38–1.02, p = 0.06).ConclusionsIn resected CC an adjuvant chemotherapy DI of > 80%, of each chemotherapy agent, is associated with improved overall survival.

Novel Strategies for Cancer Combat: Drug Combination Using Repurposed Drugs Induces Synergistic Growth Inhibition of MCF-7 Breast and HT-29 Colon Cancer Cells.

Our group developed a new model of drug combination consisting of the use of antineoplastic drugs and different repurposed drugs, having demonstrated that antimalarial and central nervous system (CNS) drugs have a promising anticancer profile as standalone agents, as well as in combined regimens. Here, we evaluated the anticancer profiles of two different CNS drugs (edaravone and quetiapine), both alone and in combination with antineoplastic agents for breast and colon cancer, to explore whether these repurposed drugs could synergistically enhance the anticancer potential of chemotherapeutic drugs. We also developed a new model of combination using two repurposed drugs, to explore whether this model of combination could also be suitable for application in breast and colon cancer therapy. MCF-7 and HT-29 cancer cells were incubated for 48 h with each individual drug (0.01–100 µM) to determine their IC50. Cells were then treated with the IC50 value for doxorubicin or paclitaxel (MCF-7) or 5-fluorouracil (HT-29) and combined with increasing concentrations of edaravone or quetiapine for 48 h. Both cell lines were also treated with a combination of two antimalarial drugs (mefloquine and pyronaridine) or two CNS drugs (fluphenazine and sertraline) for 48 h. We found that the use of quetiapine in combined therapies seems to synergistically enhance the anticancer activity of doxorubicin for the management of breast cancer. Both CNS drugs significantly improved the cytotoxic potential of 5-fluorouracil in HT-29 cells, with quetiapine synergistically interacting with the antineoplastic drug in this drug combination. Regarding the combination of repurposed drugs, only found one synergic combination regimen (sertraline IC50 plus variable concentrations of fluphenazine) with anticancer potential against HT-29 colon cancer cells was found. Taken together, these results suggest that quetiapine and edaravone can be used as adjuvant agents in chemotherapy for colon cancer. It was also found that the combination of repurposed drugs, specifically the CNS drugs sertraline and fluphenazine, may have an interesting profile for application in colon cancer novel therapies.

The Impact of Colon Cancer Sites on Survival Rates after Curative Resection and Adjuvant Chemotherapy: A SingleCenter Study

Background: Most recent studies indicate that right-sided colon cancer is associated with a significantly higher mortality rate. Multivariate analyses showed that the patient’s age, sex, mode of presentation, co-morbidity, and the stage had significantly influenced their survival. Although the primary tumor location has an impact on the overall survival in metastatic settings, the laterality of early-stage colon cancer might also affect the disease-free survival and determine the duration of adjuvant chemotherapy for each side. This study aimed to compare overall survival and disease-free survival between left-sided and right-sided high-risk stage II and stage III colon cancer in patients from a single institute. Methods: This retrospective cohort study was conducted between January 2004 and December 2017. Data on 153 patients who underwent curative resection and adjuvant chemotherapy for colon cancer were retrieved from an existing database. Results: We found that the five-year disease-free survival rates were 63.20% for left-sided colon cancer and 51.11% for right-sided colon cancer (P-value &lt; 0.05). The five-year overall survival rates were 66.98% for left-sided colon cancer and 57.77% for right-sided colon cancer (P-value 0.063). The right-sided primary tumor location was associated with a significantly higher mortality rate (HR: 2.28; 95%CI 1.38–5.8; P-value: 0.004). Conclusion: The results of this study confirmed that patients with high-risk stage II and stage III colon cancer who had right-sided tumors were significantly more likely to have decreased disease-free survival and overall survival. Further prospective studies should focus on tumor genetics and proper durations of adjuvant chemotherapy to maximize the benefit of treatment with acceptable toxicity.

Identifying the long-term survival beneficiary of chemotherapy for stage N1c sigmoid colon cancer

Sigmoid colon cancer often has an unsatisfactory prognosis. This study explored the effect of tumor deposits (TDs) on survival, and whether their presence/absence influence individualized treatment. Data of postoperative patients with sigmoid colon cancer were extracted from the Surveillance, Epidemiology, and End Results database. Overall survival (OS) was calculated using the Kaplan–Meier method and prognostic factors were identified using Cox regression analysis and random forest (RF). The nomogram's discrimination performance was evaluated using a concordance index (C-index), integrated discrimination improvement (IDI), calibration curves, and decision-curve analysis. The N1c group showed a worse prognosis than the N0 group. For N1c patients, a combination of surgery and chemotherapy prolonged survival, compared to surgery alone; however, the chemotherapy-surgery combination did not affect the OS of patients younger than 70 years, in stage T1–2, and/or of black race. Multivariable analysis and RF presented Age, T stage, and N stage were the most important predictors for OS. The novel nomogram had superiority to the TNM staging system with improved C-index and IDI, as well as good consistency and higher clinical benefit. TDs are associated with poor survival from sigmoid colon cancer, and considering TDs can inform the formulation of individual treatment regimens. The nomogram shows satisfactory prediction ability for OS.

Neoadjuvant Versus Adjuvant Chemotherapy for Resectable Metastatic Colon Cancer in Non-academic and Academic Programs.

Overall survival advantage of chemotherapy before versus after metastasectomy of liver or lung lesion is not clear for colon cancer with synchronous liver or lung metastasis. Adults 20 years or older with primary colon cancer and single organ metastatic disease either in the liver or lung at diagnosis were identified between 2010 and 2015 through the National Cancer Database (NCDB). Patients were categorized into 2 cohorts: pre-operative/peri-operative chemotherapy (neoadjuvant -[NAC]) or post-operative chemotherapy (adjuvant [AC]). Survivals and factors associated with were compared between the 2 groups. A total of 3038 patients with colon cancer with liver or lung metastases were identified. The percentage of patients receiving NAC had steadily increased from 12.29% to 28.31%, mostly in academic programs. On multivariate analysis, patients who received NAC had an overall survival advantage in the non-academic setting whereas no advantage is seen in the patients treated in the academic settings. The median overall survival for patients receiving NAC and AC was 47.24 months and 38.08 months, respectively. Factors associated with overall survival advantage in NAC patients treated in non-academic programs included age 20-49 years, CEA value of >30, right-sided colon primary, liver metastasis, and clear resection margins. Metastatic colon cancer with single organ liver or lung lesions benefits from neoadjuvant chemotherapy, especially in -non-academic settings. The overall survival advantage in this setting has not been shown before.

Estimation of colon cancer grade and metastatic lymph node involvement using DWI/ADC sequences.

The potential benefit of neoadjuvant chemotherapy (NAC) in colon cancer is under evaluation. There is a need to improve preoperative non-invasive diagnostics using techniques that provide more accurate staging information in assessing patient eligibility for NAC. To investigate the link between the tumor grade (pathohistological confirmed) and the N status (corresponding to lymph node involvement) with apparent diffusion coefficient (ADC) values. A total of 17 patients planned for surgical resection had a biopsy confirming colon carcinoma and participated in the study. Abdominal magnetic resonance imaging with diffusion-weighted imaging/ADC sequence was recorded before surgery. The tumor and all visible lymph nodes were manually delineated directly on a grayscale ADC map for every single slice and detected to access the total tumor and summarized lymph node volume. The mean ADC value was further calculated for the mean tumor and mean lymph node values. Low-grade tumors had a mean ADC equivalent to 1225 ± 170×10-6 mm2/s, and the coefficient of high-grade tumors was 1444 ± 69×10-6 mm2/s. The group of patients with positive lymph nodes in operative tissue samples (N+) exhibited lower mean ADC values (1023 ± 142×10-6 mm2/s) as opposed to the group without metastatic lymph nodes (N-) with ADC values of 1260 ± 231×10-6 mm2/s. The mean whole-tumor ADC is associated with the histological tumor grade, and the mean ADC value of whole-volume abdominal lymph nodes could assume real nodal infiltration.

High Expression of CUL9 Is Prognostic and Predictive for Adjuvant Chemotherapy in High-Risk Stage II and Stage III Colon Cancer.

Simple SummaryThis retrospective study evaluated the clinical implications of CUL9 expression on the prognosis and the predictive value for postoperative adjuvant chemotherapy in consecutive patients with colon cancer. Among all 1078 patients, high expression of CUL9 was an independent prognostic factor on disease-free survival and overall survival. Prognostic biomarkers are keys to the risk stratification of patients and the decision to recommend adjuvant chemotherapy. Among 564 patients with high-risk stage II and stage III disease who were recommended to receive the standard 6 months of chemotherapy, those with high CUL9 expression from the full dose group had better disease-free survival than those from the reduced dose group. A test for the interaction between CUL9 expression and the treatment reached significance and was not confounded by T stage, N stage and histopathological grade. This indicated that CUL9 expression may further filter those patients to identify truly high-risk cases that benefit from the full dose of the standard 6 months of chemotherapy.We evaluated the clinical implications of CUL9 expression on the prognosis and the predictive value for adjuvant chemotherapy in colon cancer. A total of 1078 consecutive patients treated with radical resection from 2008 to 2012 were included. Formalin-fixed, paraffin-embedded specimens were used as immunohistochemistry (IHC) for CUL9. For all patients, high expression of CUL9 was identified as an independent prognostic factor for overall survival (HR = 1.613, 95% CI 1.305–1.993, p < 0.001) and disease-free survival (HR = 1.570, 95% CI 1.159–2.128, p = 0.004). The prognostic value of high CUL9 expression was confirmed in an independent validation cohort from the GEO database. The efficacy of adjuvant chemotherapy was analyzed among patients with high-risk stage II and stage III disease. Those with high CUL9 expression from the full dose group had better disease-free survival (HR = 0.477, 95% CI 0.276–0.825, p = 0.006) than those from the reduced dose group. The interaction test between CUL9 expression and the treatment reached significance and was not confounded by T stage, N stage and histopathological grade. In general, high expression of CUL9 was an independent prognostic factor in patients with colon cancer. In those with high-risk stage II and stage III disease, high expression of CUL9 was associated with the benefit from standard 6-months adjuvant chemotherapy regimens.

The efficiency of neoadjuvant chemotherapy in colon cancer with mismatch repair deficiency.

Colon cancers with mismatch repair deficiency (dMMR) have specific clinicopathologic characteristics compared with mismatch repair proficiency (pMMR); however, the effect of MMR status on the efficiency of neoadjuvant chemotherapy (NCT) remains unclear. In our study, 439 dMMR and 26 pMMR colon cancer patients with or without NCT from 2010 to 2017 were retrospectively collected. Clinicopathological features, treatment response, and survival were compared between different groups. In the dMMR group, patients with NCT were likely to have higher CEA (abnormal CEA: 51.6% vs. 17.4%, p< 0.001), more multiorgan resection (38.7% vs. 16.8%, p= 0.006), and larger postoperative tumor diameter (7.26 vs. 6.21, p= 0.033) than those without NCT, but nearly half of cT4b patients who had NCT (42.9%, 9/21) avoid multiorgan resection. pT4 stage (HR, 14.97; 95% CI, 1.88-118.92; p= 0.010), number of positive lymph nodes (HR, 1.17; 95% CI, 1.09-1.26; p< 0.001), and tumor deposit (HR, 6.73; 95% CI, 2.08-21.74; p= 0.001) were independent prognosis factors of disease-free survival (DFS). For the advanced tumor subset, there is no significant difference between patients with or without NCT for OS (p= 0.13) and DFS (p= 0.11), although the survival rate of NCT was higher than non-NCT patients. Moreover, tumor regression grade was similar between dMMR and pMMR patients who had NCT. This study showed that NCT was more likely to be employed in dMMR patients with advanced tumors and may reduce the rate of multiorgan resection for cT4b dMMR patients. More large-scaled researches are needed to further explore if MMR status could predict the efficacy of neoadjuvant chemotherapy in patients with colon cancer.

Assessment of adjuvant chemotherapy benefits after complete mesocolic excision in patients with colon cancer: Reanalysis of data from the ESCME trial.

The benefits of adjuvant chemotherapy (AC) in colon cancer after complete mesocolic excision (CME) have not been evaluated sufficiently. We reanalysed the ESCME trial data to investigate the survival benefits and establish AC stratified indications. The data of Stage II and III colon cancer patients who received CME in the ESCME trial were reanalysed. Patients were divided into AC and non-AC (NAC) groups. The primary outcomes measured were differences in 5-year cancer-specific survival and disease-free survival (DFS) between the groups. Of the 206 patients enrolled in the study, 125 patients (AC, 49; NAC, 76) had Stage II cancer and 111 (AC, 86; NAC, 25) had Stage III cancer. There were no significant differences in the adjusted 5-year cancer-specific survival and DFS between the AC and NAC groups. Poor differentiation (hazard ratio [HR] 2.947; 95% CI 1.218-7.131) and RAS mutation (HR 3.140; 95% CI 1.363-7.234) affected the 5-year DFS significantly in multivariate Cox regression analysis for Stage II and III cancer, respectively. In subgroup analysis, AC significantly improved 5-year DFS (HR 0.369; 95% CI 0.140-0.978) for Stage III cancer with lymphovascular/perineural invasion compared to NAC. The current indication and benefits of AC for colon cancer patients after CME should be re-evaluated. AC is more appropriate for Stage III cancer with lymphovascular/perineural invasion.

Second Cancer After Additive Chemotherapy in Patients With Colon Cancer

BackgroundAdditive chemotherapeutic treatment of UICC-stage -III / IV colon cancer with fluorouracil, leucovorin and oxaliplatin is widely accepted as current standard of treatment after R0-resection. However, as patients.. survival is increasing, long-term side effects of chemotherapeutic agents such as second cancer development are becoming increasingly important. PatientsWe therefore investigated a total of 2 856 Patients with UICC-stage III / IV colon cancer, 223 of whom (7.8%) had developed a subsequent second cancer. ResultsMedian follow-up was 73.2 months (range 209.9 months, 95%-CI 69.8-76.9). Most frequent second cancers were prostate cancer (18.4%), colon cancer (16.1%), breast cancers (8.1%), lung cancer (8.1%), rectal cancer (4.9%) and uterine cancer (4.9%). However, in comparison to non-treated patients this did not represent a significantly increased risk for subsequent second cancer in patients after treatment with additive chemotherapy. Of interest, our data suggest a significantly decreased second cancer rate in patients treated with FOLFOX compared to FUFOL for additive treatment. ConclusionsSecond cancer development was not increased after additive chemotherapy for colon cancer, which is a novel aspect in the ongoing discussions on reduction of adjuvant treatment to 3 months or treatment of lymph node negative patients.Novelty and Impact StatementTo our knowledge, this is the first population-based study analyzing second cancer development after additive chemotherapy in patients with UICC III-IV colon cancer. The results have an important impact on the surveillance and long-term follow-up of cancer patients.

The Prognostic Value of Adjuvant Chemotherapy in Colon Cancer With Solitary Tumor Deposit.

PurposeThe aim of this study is to investigate the survival benefit of adjuvant chemotherapy in patients with colon cancer with the solitary tumor deposit (TD).MethodsThe primary study outcomes used in this study were colon cancer–specific survival (CSS) and overall survival (OS). The differences of the distribution of categorical variables in patients with colon cancer with the solitary TD according to adjuvant chemotherapy administration were tested using the Pearson’s chi-square test. The Kaplan–Meier method was utilized to evaluate CSS and OS. Hazard ratio (HR) and 95% confidence interval (CI) were calculated on the basis of Cox regression models to assess the prognostic value of different demographic and clinicopathological characteristics.ResultsA total of 877 patients with TanyN1cM0 colon cancer with solitary TD were identified in our analysis. It was found that OS (75.4% vs. 42.8% for 5-year OS rate, p < 0.001) and CSS (82.9% vs. 69.3% for 5-year CSS rate, p < 0.001) of patients with colon cancer with adjuvant chemotherapy administration were significantly better than those without adjuvant chemotherapy administration. Multivariate Cox survival analyses revealed that the overall and colon cancer–specific mortality risks of patients with adjuvant chemotherapy administration were decreased by 64.4% (HR = 0.356, 95% CI = 0.265–0.479, p < 0.001) and 57.4% (HR = 0.426, 95% CI = 0.286–0.634, p < 0.001) compared with those without adjuvant chemotherapy administration, respectively.ConclusionsAdjuvant chemotherapy administration could significantly improve OS and CSS in patients with colon cancer with the solitary TD. This is the first study to investigate and demonstrate the survival benefit of adjuvant chemotherapy in patients with colon cancer with the solitary TD.

Establishment of a Necroptosis Related Genes Signature to Predict Prognosis and Therapeutic Response in Colon Cancer.

Necroptosis, as a form of programmed cell death, is involved in many physiological and pathological processes. However, its role in cancer progression and therapeutic response remains controversial. Colon cancer is one of the leading causes of cancer death and patients’ response to immune checkpoint blockade vary to a large degree. In this study, we investigated necroptosis related genes (NRGs) alterations in colon cancer by bioinformatics analysis. Colon cancer patients were classified into two subtypes with distinct clinical and molecular features based on NRGs. After finding differentially expressed genes and lasso regression, a prognostic model based on four necroptosis signature genes was constructed. The necroptosis signature was also a good predictor in the field of chemotherapy and immunotherapy in colon cancer. Altogether, this study illustrates the relationship between necroptosis and colon cancer, and establishes a novel scoring method to predict prognosis and therapeutic response in colon cancer patients.