Is prognosis uniformly excellent in patients with stage II MSI-high colon cancer?
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ABSTRACT:
SUBMITTER: Wang J
PROVIDER: S-EPMC9577717 | biostudies-literature | 2022 Sep
REPOSITORIES: biostudies-literature
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Is prognosis uniformly excellent in patients with stage II MSI-high colon cancer?
Wang Jane J Margonis Georgios Antonios GA
Annals of translational medicine 20220901 18
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Project description:Cancer metastases accounts for most cancer deaths. The secreting glycoprotein Wnt5a impairs tumor cell migration and reduces invasiveness and metastasis. High Wnt5a expression in tumor cells is correlated to better outcomes in patients with breast, prostate and epithelial ovarian cancer. We aimed to investigate the association between the Wnt5a expression and outcomes in patients with colon cancer (CC) stage II/III. We performed a retrospective single-center study evaluating 345 patients with radical resection for primary CC, stage II/III, who started 6 months of adjuvant chemotherapy with 5-FU or capecitabine ± oxaliplatin between 2001 and 2015. Archived formalin-fixed paraffin embedded tumor tissue from resection specimens were stained with Wnt5a antibody using immunohistochemistry. Cytoplasmatic Wnt5a staining was assessed according to intensity and percentage of stained cells. Patients were divided in groups depending on high (n = 230) or low (n = 115) Wnt5a expression. Disease free survival (DFS) and overall survival (OS) were analyzed for the two groups using Kaplan-Meier plots and Long rank test. Patients with Wnt5a-negative tumors had significantly poorer performance status (PS) than patients with high Wnt5a expression (p = 0.046). No significant difference was seen between patients with low and high Wnt5a expression in terms of 5-year DFS (p = 0.517) or 5-year OS (p = 0.415). Poor PS was associated with lower DFS (p = 0.002) and OS (p < 0.001). In conclusion, we found no significant difference in prognosis for patients with stage II/III CC depending on their Wnt5a expression. Patients with Wnt5a-negative tumors had significant poorer PS than patients with higher levels. Poor PS was associated with lower DFS and OS.
| S-EPMC7553443 | biostudies-literature
Project description:Stage II colon cancer (CC) is probably one of the best prognosis gastrointestinal tumors seen in our consultations, but often takes a lot of time for physicians to determine appropriate treatment because of the limited benefit of adjuvant chemotherapy (CT) in these patients, together with the limited evidence in this situation. How to choose the best treatment for each individual patient is thus dependent on molecular (microsatellite instability/microsatellite stability status) and clinico-pathological features relevant enough to classify these tumors into low-, intermediate- and high-risk stage II disease and to choose an appropriate attitude for each of these subgroups. In practice, the first step in treatment decision making must be to assess the patient's status and comorbidities to see if the patient is eligible for an adjuvant treatment. Then, as fluoropyrimidines (FPs) are the corner stone of CC adjuvant treatment, screening for dihydropyrimidine dehydrogenase deficiency is mandatory in western countries. Finally, depending on the patient's characteristics and tumor risk stage, the strategy may be surveillance, adjuvant FP alone or oxaliplatin-based adjuvant CT. In the near future, new tools such as Immunoscore® (HalioDx; Luminy Biotech Enterprises, Marseille Cedex, France) and circulating tumor DNA may help to identify more precisely patients with minimal residual disease for more personalized adjuvant treatment approaches.
| S-EPMC8264531 | biostudies-literature
Project description:Lipid metabolism plays an essential role in carcinogenesis due to the requirements of tumoral cells to sustain increased structural, energetic and biosynthetic precursor demands for cell proliferation. We investigated the association between expression of lipid metabolism-related genes and clinical outcome in intermediate-stage colon cancer patients with the aim of identifying a metabolic profile associated with greater malignancy and increased risk of relapse. Expression profile of 70 lipid metabolism-related genes was determined in 77 patients with stage II colon cancer. Cox regression analyses using c-index methodology was applied to identify a metabolic-related signature associated to prognosis. The metabolic signature was further confirmed in two independent validation sets of 120 patients and additionally, in a group of 264 patients from a public database. The combined analysis of these 4 genes, ABCA1, ACSL1, AGPAT1 and SCD, constitutes a metabolic-signature (ColoLipidGene) able to accurately stratify stage II colon cancer patients with 5-fold higher risk of relapse with strong statistical power in the four independent groups of patients. The identification of a group of 4 genes that predict survival in intermediate-stage colon cancer patients allows delineation of a high-risk group that may benefit from adjuvant therapy, and avoids the toxic and unnecessary chemotherapy in patients classified as low-risk group.
| S-EPMC4466690 | biostudies-literature
Project description:BackgroundStage II colon cancer has varying risks for metastasis, and treatment strategies depend on molecular and clinicopathological features. While tumor-sidedness is a well-accepted prognostic factor for stage III/IV colon cancer, its role in stage II is controversial. Understanding its effect in stage II is crucial for improving treatment strategies.MethodsWe analyzed clinical and follow-up data of colon cancer from the Surveillance, Epidemiology, and End Results database (2004-2017). Patients were divided into a primary study cohort (2010-2017) and a validation cohort (2004-2009). The baseline characteristics between right-sided colon cancer (RCC) and left-sided colon cancer (LCC) groups were compared. Moreover, the effect of tumor size on cancer-specific survival (CSS) was evaluated using Kaplan-Meier analysis.ResultsThe study involved 87,355 patients in the study cohort and 65,858 in the validation cohort. Of the study cohort, 52.3% were diagnosed with RCC. The median age was 64 years old, with 48.5% females and 76.8% of white people. In addition, stage II RCC showed better CSS compared with LCC (5-year CSS 88.0% vs 85.5%, P < 0.001), while stage III/IV RCC demonstrated poorer outcomes. Multivariate Cox regression analysis identified that the right-sidedness was a positive prognostic factor in stages I/II but negative in stages III (HR 1.10, P < 0.001) and IV (HR 1.26, P < 0.001). Chemotherapy rates decreased in RCC, particularly in stage II (RCC vs LCC: 16.2% vs 28.5%, P < 0.001). Subgroup analysis, stratified by T3/T4 stages and chemotherapy status, further highlighted better survival outcomes in RCC.ConclusionsRCC is associated with a significantly better prognosis in stage II. The importance of considering tumor-sidedness in clinical decision-making and the design of future clinical trials should be emphasized.
| S-EPMC11014780 | biostudies-literature
Project description:Background: The impact of tumor size on the survival and chemotherapy reponse of early-stage colon cancer remains unclear. Our study explored the effect of tumor size on overall survival (OS) and postoperative chemotherapy efficacy in patients with stage I/II colon cancer. Methods: Stage I/II colon cancer patients from the Surveillance, Epidemiology and End Results (SEER) database and a China center were extracted as two cohorts respectively. X-tile program was adopted to acquire optimal cutoff points of tumor size (16mm and 49mm). Harrell's concordance index (c-index) and time-dependent receiver operating characteristic curve (ROC) were used to indicate discrimination ability of prognostic factors. Results: Overall, 104,908 and 168 stage I/II postoperative colon cancer patients from SEER database and a China center were eligible, respectively. Kaplan-Meier analysis showed that large tumor size was associated with poor OS in two cohorts. The effect of tumor size on OS gradually decreased as the T stage increased both before PSM (c-index 0.535 for T1N0M0 and 0.506 for T4N0M0, p<0.05) and after PSM (c-index 0.543 for T1N0M0, p<0.05; c-index 0.543 for T4N0M0, p>0.05). Stratified analyses showed that chemotherapy improved the OS rate by 9.5% (chemotherapy vs. non-chemotherapy: 83.5% vs. 73.0%) or 12.8% (chemotherapy vs. non-chemotherapy: 85.7% vs. 72.9%) before and after PSM in T2N0M0 patients with tumor size >49 mm, but not in T1N0M0. The survival benefit provided by chemotherapy for T2N0M0 patients with large tumor was also validated in the Chinese cohort. Conclusions: Large tumor size was a risk factor for stage I/II colon cancer, especially for T1N0M0. Tumor size could serve as a complementary factor guiding postoperative chemotherapy for T2N0M0 patients.
| S-EPMC11310877 | biostudies-literature
Project description:The presence of lymph node metastases remains the most reliable prognostic predictor and the gold indicator for adjuvant treatment in colon cancer (CC). In spite of a potentially curative resection, 20 to 30% of CC patients testing negative for lymph node metastases (i.e. pN0) will subsequently develop locoregional and/or systemic metastases within 5 years. The presence of occult nodal isolated tumor cells (ITCs) and/or micrometastases (MMs) at the time of resection predisposes CC patients to high risk for disease recurrence. These pN0(micro+) patients harbouring occult micrometastases may benefit from adjuvant treatment. The purpose of the present study is to delineate the subset of pN0 patients with micrometastases (pN0(micro+)) and evaluate the benefits from adjuvant chemotherapy in pN0(micro+) CC patients.EnRoute+ is an open label, multicenter, randomized controlled clinical trial. All CC patients (age above 18 years) without synchronous locoregional lymph node and/or systemic metastases (clinical stage I-II disease) and operated upon with curative intent are eligible for inclusion. All resected specimens of patients are subject to an ex vivo sentinel lymph node mapping procedure (SLNM) following curative resection. The investigation for micrometastases in pN0 patients is done by extended serial sectioning and immunohistochemistry for pan-cytokeratin in sentinel lymph nodes which are tumour negative upon standard pathological examination. Patients with ITC/MM-positive sentinel lymph nodes (pN0(micro+)) are randomized for adjuvant chemotherapy following the CAPOX treatment scheme or observation. The primary endpoint is 3-year disease free survival (DFS).The EnRoute+ study is designed to improve prognosis in high-risk stage I/II pN0(micro+) CC patients by reducing disease recurrence by adjuvant chemotherapy.ClinicalTrials.gov: NCT01097265.
| S-EPMC3123166 | biostudies-literature
Project description:BackgroundPatients with UICC/AJCC stage II colon cancer have a high 5-year overall survival rate after surgery. Nevertheless, a significant subgroup of patients develops tumour recurrence. Currently, there are no clinically established biomarkers available to identify this patient group. We applied reverse-phase protein arrays (RPPA) for phosphatidylinositide-3-kinase pathway activation mapping to stratify patients according to their risk of tumour recurrence after surgery.MethodsFull-length proteins were extracted from formalin-fixed, paraffin-embedded tissue samples of 118 patients who underwent curative resection. RPPA technology was used to analyse expression and/or phosphorylation levels of six major factors of the phosphatidylinositide-3-kinase pathway. Oncogenic mutations of KRAS and BRAF, and DNA microsatellite status, currently discussed as prognostic markers, were analysed in parallel.ResultsExpression of phospho-AKT (HR=3.52; P=0.032), S6RP (HR=6.3; P=0.044), and phospho-4E-BP1 (HR=4.12; P=0.011) were prognostic factors for disease-free survival. None of the molecular genetic alterations were significantly associated with prognosis.ConclusionsOur data indicate that activation of the PI3K/AKT pathway evidenced on the protein level might be a valuable prognostic marker to stratify patients for their risk of tumour recurrence. Beside adjuvant chemotherapy targeting of upregulated PI3K/AKT signalling may be an attractive strategy for treatment of high-risk patients.
| S-EPMC3992486 | biostudies-literature
Project description:BackgroundWe evaluated the prognostic role of deficient mismatch repair (dMMR) systems in stage II and stage III colon cancer patients during different postoperative periods. We also assessed whether patients aged ≥75 could benefit from chemotherapy.MethodsThis retrospective study was conducted across three medical centers in China. Kaplan-Meier survival methods and Cox proportional hazards models were used to evaluate the differences in overall survival (OS) and disease-free survival (DFS) rates. Propensity score matching was performed to reduce imbalances in the baseline characteristics of the patients. Landmark analysis was performed to evaluate the role of dMMR during different postoperative periods.ResultsThe median follow-up time for all patients was 45.0 months (25-75 IQR: 38.0-82.5). There was no significant OS (p = 0.350) or DFS (p = 0.752) benefit associated with dMMR for stage II and III patients during the first postoperative year. However, significant OS (p < 0.001) and DFS (p < 0.001) benefits were observed from the second postoperative year until the end of follow-up. These differences remained after propensity score matching. Moreover, chemotherapy produced no OS (HR = 0.761, 95% CI: 0.43-1.34, p = 0.341) or DFS (HR = 0.98, 95% CI: 0.51-1.88, p = 0.961) benefit for patients aged ≥75 years.ConclusionThe benefits of dMMR in stage III patients were observed from the second postoperative year until the end of follow-up. However, the prognosis of patients with dMMR is not different from that of patients with proficient mismatch repair (pMMR) during the first postoperative year. In addition, elderly patients aged ≥75 years obtained no significant survival benefits from postoperative chemotherapy.
| S-EPMC9648020 | biostudies-literature
Project description:Decisions regarding adjuvant therapy in patients with stage II colon cancer remains controversial and challenging. We aimed to determine novel biomarkers that help to predict relapse free survival (RFS) and identify a subset of patients with stage II colon cancer who could gain survival benefits from adjuvant chemotherapy. Public microarray datasets of stage II colon cancer samples were extracted from Gene Expression Omnibus database. Global gene expression changes were then analyzed between the paired early relapse and long-term survival group to identify the differentially expressed mRNAs and lncRNAs. Based on Lasso Cox regression modeling analysis, a total of 30 mRNAs and 2 lncRNAs were finally identified. With specific formula, stage II patients in training and validation sets were divided into low and risk groups with significantly different RFS. PAX8-AS1 is the novel lncRNA which showed the highest upregulation in early relapse group. Patients with high PAX8-AS1 expression level showed notably poorer RFS in both meta GEO cohort (P = 0.04, Figure 4B) and FUSCC cohort (P < 0.001, Figure 4C). Among the stage II patients with high PAX8-AS1 level, administration of fluorouracil-based adjuvant chemotherapy provided a substantial improvement in RFS (P = 0.002, Figure 3C). Further mechanistic study unveiled that PAX8-AS1 increases the response of CRC cells to chemotherapy in vitro and in vivo by maintaining the mRNA stability of PAX8. In conclusion, PAX8-AS1 as a novel and reliable biomarker for predicting prognosis and identification of patients with stage II disease who could gain survival benefit from fluorouracil-based adjuvant chemotherapy.
| S-EPMC11437868 | biostudies-literature
Project description:Postoperative carcinoembryonic antigen (post-CEA) has recently been reported to be a reliable prognostic factor for colon cancer. However, most clinicians decide whether or not to conduct adjuvant chemotherapy (AC) for stage II colon cancer according to major guidelines, which do not include post-CEA in their high-risk criteria. The present study aimed to assess post-CEA in stage II colon cancer for which the significance of AC is unknown. The present study analyzed 199 consecutive patients with stage II colon cancer who underwent curative surgery between January 2007 and December 2016. The CEA value was considered high when it was ≥5.0 ng/ml. The prognostic value of high post-CEA values was assessed. Overall, 19 patients exhibited high post-CEA levels. Kaplan-Meier survival curve analysis demonstrated that patients with high post-CEA levels had significantly worse relapse-free survival (RFS) and overall survival (OS) than those with normal post-CEA [RFS, 63.5 (high post-CEA) vs. 88.0% (normal post-CEA), P=0.003; OS, 76.5 (high post-CEA) vs. 96.8% (normal post-CEA), P<0.001]. Multivariate analysis demonstrated that high post-CEA remained a significant independent risk factor for worse RFS [hazard ratio (HR), 3.98; P=0.006]. The same was also demonstrated for patients without AC (HR, 5.43; P=0.008). To the best of our knowledge, the present study was the first to demonstrate that high post-CEA levels may be an indicator of high-risk stage II colon cancer, even for patients without AC. These results highlight the need for a multicenter prospective study.
| S-EPMC8988258 | biostudies-literature