Adjuvant therapy for T3N0 rectal cancer in the total mesorectal excision era- identification of the high risk patients

<p>Abstract</p> <p>Background</p> <p>Adjuvant therapy for T3N0 rectal cancer was controversial with respect to both radiation and the use of a combined regimen of chemotherapy. We evaluated both clinical features and biomarkers and sought to determine risk factors for those patients retrospectively.</p> <p>Methods</p> <p>A total of 122 patients with T3N0 rectal cancer were analyzed in this study from January 2000 to December 2005. Clinicopathologic and biomarkers were used to predict local recurrence (LR), disease-free survival (DFS), and overall survival (OS).</p> <p>Results</p> <p>The median follow-up interval was 45.4 months. Five-year LR, DFS, and OS rates were 10.4%, 68.3%, and 88.7%. Having a lower tumor location and showing low P21 and high CD44v6 expression were identified as risk factors for LR: patients with two or three of these risk factors had a higher 5-year LR rate (19.3%) than did patients with none or one of these risk factors (6.8%) (p = 0.05). A poorer DFS was related to low P21 nor high CD44v6 expression but not to tumor location: the 5-year DFS rates were 79.3% for those with neither, 65.9% for those with either one or the other, and 16.9% for those with both (p = 0.00).</p> <p>Conclusions</p> <p>The prognostic model including tumor location, P21 and CD44v6 expressions could help to distinguish these patients with high risk T3N0 patients and determine whether adjuvant therapy was beneficial.</p

Bis(2-meth­oxy-6-{[2-(methyl­ammonio)eth­yl]imino­meth­yl}phenolato)thio­cyanato­zinc(II) thio­cyanate hemihydrate

The title mononuclear zinc(II) complex, [Zn(C11H16N2O2)2(NCS)]NCS·0.5H2O, consists of a complex cation, a thio­cyanate anion, and half of a water mol­ecule. The ZnII atom in the cation is five-coordinated by two imine N and two phenolate O atoms from two bidentate Schiff base ligands, and by one N atom of a thio­cyanate ligand, forming a distorted trigonal-bipyramidal geometry. The ammonio H atoms are involved in hydrogen bonding with the ligand O atoms and the solvent water molecules (site occupation factor 0.5), which partially determines the conformation of the ligands

Early results of quality of life for curatively treated rectal cancers in Chinese patients with EORTC QLQ-CR29

<p>Abstract</p> <p>Purpose</p> <p>To assess the quality of life in curatively treated patients with rectal cancer in a prospectively collected cohort.</p> <p>Methods</p> <p>Patients with stage I-III rectal cancer who were treated curatively in a single institution were accrued prospectively. Quality of life was assessed by use of the European Organization for Research and Treatment of Cancer questionnaire module for all cancer patients (QLQ-C30) and for colorectal cancer patients (QLQ-CR29). Quality of life among different treatment modalities and between stoma and nonstoma patients was evaluated in all patients.</p> <p>Results</p> <p>A total of 154 patients were assessed. The median time of completion for the questionnaires was 10 months after all the treatments. For patients with different treatment modalities, faecal incontinence and diarrhea were significantly higher in radiation group (p = 0.002 and p = 0.001, respectively), and no difference in male or female sexual function was found between radiation group and non-radiation group. For stoma and nonstoma patients, the QLQ-CR29 module found the symptoms of Defaecation and Embarrassment with Bowel Movement were more prominent in stoma patients, while no difference was detected in scales QLQ-C30 module.</p> <p>Conclusions</p> <p>Our study provided additional information in evaluating QoL of Chinese rectal cancer patients with currently widely used QoL questionnaires. As a supplement to the QLQ-C30, EORTC QLQ-CR29 is a useful questionnaire in evaluating curatively treated patients with rectal cancer. Bowel dysfunction (diarrhea and faecal incontinence) was still the major problem compromising QoL in patients with either pre- or postoperative chemoradiotherapy.</p

Higher FOXP3-TSDR demethylation rates in adjacent normal tissues in patients with colon cancer were associated with worse survival

BACKGROUND: The influence of natural regulatory T cells (nTregs) on the patients with colon cancer is unclear. Demethylated status of the Treg-specific demethylated region (TSDR) of the FOXP3 gene was reported to be a potential biomarker for the identification of nTregs. METHODS: The demethylation rate of the TSDR (TSDR-DMR) was calculated by using methylation-specific quantitative polymerase chain reaction (MS-qPCR) assay. The expression of TSDR-DMR and FOXP3 mRNA was investigated in various colorectal cancer cell lines. A total of 130 colon carcinoma samples were utilized to study the DMR at tumor sites (DMR(T)) and adjacent normal tissue (DMR(N)). The correlations between DMRs and clinicopathological variables of patients with colon cancer were studied. RESULTS: The TSDR-DMRs varied dramatically among nTregs (97.920 ± 0.466%) and iTregs (3.917 ± 0.750%). Significantly, DMR(T) (3.296 ± 0.213%) was higher than DMR(N) (1.605 ± 0.146%) (n = 130, p = 0.000). Higher DMR(N) levels were found in female patients (p = 0.001) and those with distant metastases (p = 0.017), and were also associated with worse recurrence-free survival in non-stage IV patients (low vs. high, p = 0.022). However, further Cox multivariate analysis revealed that the FOXP3-TSDR status does not have prognostic value. CONCLUSION: MS-qPCR assays of FOXP3-TSDR can efficiently distinguish nTregs from non-nTregs. Abnormal recruitment of nTregs occurs in the local tumor microenvironment. Infiltration of tissue-resident nTregs may have a negative role in anti-tumor effects in patients with colon cancer; however, this role is limited and complicated

Prognostic and Predictive Value of CpG Island Methylator Phenotype in Patients with Locally Advanced Nonmetastatic Sporadic Colorectal Cancer

Purpose. In the present study, the prognostic significance of CpG island methylator phenotype (CIMP) in stage II/III sporadic colorectal cancer was evaluated using a five-gene panel. Methods. Fifty stage II/III colorectal cancer patients who received radical resection were included in this study. Promoter methylation of p14ARF, hMLH1, p16INK4a, MGMT, and MINT1 was determined by methylation specific polymerase chain reaction (MSP). CIMP positive was defined as hypermethylation of three or more of the five genes. Impact factors on disease-free survival (DFS) and overall survival (OS) were analyzed using Kaplan-Meier method (log-rank test) and adjusted Cox proportional hazards model. Results. Twenty-four percent (12/50) of patients were characterized as CIMP positive. Univariate analysis showed stage III (P=0.049) and CIMP positive (P=0.014) patients who had significantly inferior DFS. In Cox regression analysis, CIMP positive epigenotype was independently related with poor DFS with HR = 2.935 and 95% CI: 1.193–7.220 (P=0.019). In patients with CIMP positive tumor, those receiving adjuvant chemotherapy had a poor DFS than those without adjuvant chemotherapy (P=0.023). Conclusions. CIMP positive was significantly correlated with decreased DFS in stage II/III colorectal cancer. Patients with CIMP positive locally advanced sporadic colorectal cancers may not benefit from 5-fluorouracil based adjuvant chemotherapy

Evaluating the Guiding Role of Elevated Pretreatment Serum Carcinoembryonic Antigen Levels for Adjuvant Chemotherapy in Stage IIA Colon Cancer: A Large Population-Based and Propensity Score-Matched Study

Objective: This study was to investigate guiding role of elevated pretreatment serum carcinoembryonic antigen (CEA) levels for ACT receipt in stage IIA colon cancer.Methods: Eligible patients diagnosed with stage IIA colon cancer (N = 21848) were identified from the Surveillance, Epidemiology, and End Results (SEER) database between January 2004 and December 2010. Pearson's chi-squared tests, Cox proportional hazards regression models, and Kaplan-Meier methods were performed. Propensity score matching (PSM) was used to decrease the risk of biased estimates of treatment effect.Results: Multivariate Cox analysis indicated that, in CEA-elevated group, receiving or not receiving ACT did not presented statistically CSS difference [hazard ratio (HR) = 0.940, 95% confidence interval (CI) = 0.804–1.097, P = 0.431]; in CEA-normal group, receiving or not receiving ACT also did not presented statistically CSS difference (HR = 0.911, 95% CI = 0.779–1.064, P = 0.239). After PSM, Kaplan-Meier analyses showed that there was no statistical CSS difference between receiving or not receiving ACT (P = 0.64).Conclusion: ACT did not show substantial survival benefit in stage IIA colon cancer with elevated pretreatment serum CEA levels. Stage IIA disease with elevated pretreatment serum CEA should not be treated with ACT

Patient-derived organoids as a platform for drug screening in metastatic colorectal cancer

Introduction: Most advanced colorectal cancers are aggressive, and there is a lack of effective methods for selecting appropriate anticancer regimens. Patient-derived organoids (PDOs) have emerged as preclinical platforms for modeling clinical responses to cancer therapy.Methods: In this study, we successfully constructed a living biobank with 42 organoids derived from primary and metastatic lesions of metastatic colorectal cancer patients. Tumor tissue was obtained from patients undergoing surgical resection of the primary or metastatic lesion and then used to establish PDOs. Immunohistochemistry (IHC) and drug sensitivity assays were performed to analyze the properties of these organoids.Results: The mCRC organoids were successfully established with an 80% success rate. The PDOs maintained the genetic and phenotypic heterogeneity of their parental tumors. The IC50 values of5-fluorouracil (5-FU), oxaliplatin, and irinotecan (CPT11) were determined for mCRC organoids using drug sensitivity assays. The in vitro chemosensitivity data revealed the potential value of PDOs for clinical applications in predicting chemotherapy response and clinical outcomes in mCRC patients.Discussion: In summary, the PDO model is an effective platform for in vitro assessment of patient-specific drug sensitivity, which can guide personalized treatment decisions for patients with end-stage CRC

Neoadjuvant chemoradiotherapy combined with immunotherapy for locally advanced rectal cancer: A new era for anal preservation

For locally advanced (T3-4/N+M0) rectal cancer (LARC), neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard treatment. It was demonstrated to decrease the local recurrence rate and increase the tumor response grade. However, the distant metastasis remains an unresolved issue. And the demand for anus preservation and better quality of life increases in recent years. Radiotherapy and immunotherapy can be supplement to each other and the combination of the two treatments has a good theoretical basis. Recently, multiple clinical trials are ongoing in terms of the combination of nCRT and immunotherapy in LARC. It was reported that these trials achieved promising short-term efficacy in both MSI-H and MSS rectal cancers, which could further improve the rate of clinical complete response (cCR) and pathological complete response (pCR), so that increase the possibility of ‘Watch and Wait (W&amp;W)’ approach. However, the cCR and pCR is not always consistent, which occurs more frequent when nCRT is combined with immunotherapy. Thus, the efficacy evaluation after neoadjuvant therapy is an important issue for patient selection of W&amp;W approach. Evaluating the cCR accurately needs the combination of multiple traditional examinations, new detective methods, such as PET-CT, ctDNA-MRD and various omics studies. And finding accurate biomarkers can help guide the risk stratification and treatment decisions. And large-scale clinical trials need to be performed in the future to demonstrate the surprising efficacy and to explore the long-term prognosis