Tumor budding is a strong predictor of disease-free survival in stage II colorectal cancer: Validation study based on the International Tumor Budding Consensus Conference (ITBCC) recommendations.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 594-594 ◽  
Author(s):  
Heather Dawson ◽  
Naziheh Assarzadegan ◽  
Robert Riddell ◽  
Richard Kirsch ◽  
Annika Blank ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Tumor Cells ◽  
Disease Free Survival ◽  
The United States ◽  
Consensus Conference ◽  
Stage Ii ◽  
Tumor Budding ◽  
Free Survival ◽  
Staging Systems ◽  
Disease Free

594 Background: Tumor budding, defined as single tumor cells or small clusters of four or less tumor cells at the invasive front, has been shown to be a strong and independent prognostic factor in colorectal cancer (CRC). However, widespread reporting of tumor budding has been held back largely due to a lack of consensus on scoring methods. 23 experts from the United States, Canada, Japan and Europe participated at the International Tumor Budding Consensus Conference (ITBCC), held in April 2016 in Bern, Switzerland, and agreed on a set of recommendations for assessing and reporting tumor budding in CRC. The aim of this study was to validate the method proposed by ITBCC in the clinically relevant scenario of Stage II CRC. Methods: In 151 Stage II CRC patients, tumor budding was assessed on scanned H&E-stained slides in a single hot spot measuring 0.785mm2. Cutoffs as defined by ITBCC were used: Low (Bd1): 0-4 buds, intermediate (Bd2): 5-9 buds, high (Bd3): ≥ 10 buds. Statistical analysis for associations with clinicopathological features, disease free survival (DFS) and overall survival (OS) was performed. Results: The average number of buds/hotspot was 6.8 (median 5.0). 43.1% of cases were Bd1, 27.2% Bd2 and 29.8% Bd3. Tumor budding as a continuous variable was associated with extramural venous invasion (EMVI) (p = 0.05). Tumor budding was associated with poorer OS in univariate analysis (p = 0.0386, HR 1.048, 95%CI 1.002-1.095). For 3- and 5- year DFS, Bd3 was associated with significantly worse survival in comparison with Bd1/2 (p = 0.0031 and p = 0.0025, respectively). In multivariate analysis adjusting for pT, tumor grade and EMVI, tumor budding retained its adverse prognostic effect for DFS (p = 0.006, HR 3.293, 95%CI 1.66-6.53). Conclusions: This study provides promising data on tumor budding assessed by the ITBCC method in the Stage II scenario. Especially Bd3 shows a detrimental adverse impact on DFS in comparison to Bd1/Bd2. Based on the ITBCC, tumor budding has the potential to strongly affect the management of Stage II CRC patients and should be therefore included in reporting guidelines and staging systems in CRC.

Circulating tumor DNA as a promising biomarker of relapse risk for stage II-III colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4079-4079
Author(s):  
Gong Chen ◽  
Feng Wang ◽  
Jun-Jie Peng ◽  
San-Jun Cai ◽  
Ke-Feng Ding ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Curative Resection ◽  
Disease Free Survival ◽  
Early Recurrence ◽  
Circulating Tumor Dna ◽  
Stage Ii ◽  
Free Survival ◽  
Colorectal Cancer Patients ◽  
Disease Free ◽  
Tumor Dna

4079 Background: About 30-50% colorectal cancer patients undergoing a curative resection will experience disease recurrence ultimately. Early detection of recurrence is of great significance for improving the prognosis of colorectal cancer patients. Circulating tumor DNA (ctDNA) has been suggested to be a promising biomarker for postoperative surveillance and prognosis prediction in various cancers including colorectal cancer. However, its performance in predicting early recurrence of colorectal cancer as well as appropriate testing procedures still needs large-scale prospective studies to evaluate. Methods: A total of 246 patients with stage II-III colorectal cancer and underwent curative resection from three clinical centers of China were enrolled in this multicenter prospective cohort study. Tissue samples as well as serial plasma samples before surgery, 7 days and 6 months after surgery and 3 months interval afterwards until recurrence were collected, and subjected to deep targeted-panel sequencing containing 425 cancer-related genes. ctDNA baseline genomic alterations and dynamic changes were analyzed. Its performance in predicting early recurrence was evaluated and compared with other clinical routine investigations, including serum biomarkers CEA and CA199, and CT examination. Results: The ctDNA positive rates at baseline (before surgery) and 7 days after surgery were 72.9% and 18.1% respectively. Among 199 patients with complete survival data, 18 patients were recurrent during follow up period with a median disease-free survival of 280.5 days (114-461 days). At baseline, high clinical stage (p = 0.035), and PTEN mutation (p = 0.009) were significantly associated with increased recurrent risk; while APC mutation (p = 0.04) predicted a decreased recurrent risk. Detection of ctDNA 7 days after surgery [HR: 5.9 (1.94-17.97); p = 0.0004] or any time point before clinical recurrence [HR: 6.14 (2.3-16.38); p < 0.0001] was associated with a significantly higher recurrent risk, and the HR increased accordingly with ctDNA mutation level. In multivariate analyses, ctDNA status was independently associated with relapse after adjusting for known clinicopathological risk factors. CEA status was not significantly (p > 0.4) associated with disease-free survival. A risk scoring model comprising of clinical variables and ctDNA detection after surgery was constructed and can predict 18-month recurrence with an AUC of 0.77. Conclusions: ctDNA is a promising marker of risk stratification, and early relapse detection in resected stage II/III CRC patients. Clinical trial information: NCT03312374 .

The Treatment of Hepatic Metastases in Colorectal Carcinoma

2006 ◽  
Vol 72 (6) ◽  
pp. 466-473
Author(s):  
Angela M. Lewis ◽  
Robert C.G. Martin
Keyword(s):  
Colorectal Cancer ◽  
Colorectal Carcinoma ◽  
Metastatic Colorectal Cancer ◽  
Treatment Options ◽  
Hepatic Metastases ◽  
Disease Free Survival ◽  
The United States ◽  
Paradigm Shifts ◽  
Free Survival ◽  
Disease Free

Colorectal carcinoma is the third most common cause of cancer death in the United States, with 135,000 new cases and 55,000 deaths annually. Ultimately, two-thirds (99,000) of all patients with colorectal cancer will develop metastasis to the liver and other organs in their life span, making metastatic colorectal cancer the second leading cause of cancer-related death in North America. The optimal management of these patients has become increasingly complex with the myriad of treatment options that are available. Because the timing of any therapy (surgery, chemotherapy, or others) has become integral to the success of the treatment, a collaborative approach involving multiple specialties is needed for the best patient outcome. Defined clinical and pathologic determinants of outcome have been demonstrated to effect the overall and disease-free survival of patients with metastatic colorectal cancer. Understanding of these determinants remains essential to any treating physician and has lead to significant paradigm shifts in the management of patients with metastatic colorectal cancer.

scholarly journals A SMAD4 ‐modulated gene profile predicts disease‐free survival in stage II and III colorectal cancer

2021 ◽  
Author(s):  
Bryan C. Szeglin ◽  
Chao Wu ◽  
Michael R. Marco ◽  
Hyun Sung Park ◽  
Zeda Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Gene Profile ◽  
Free Survival ◽  
Disease Free

scholarly journals A SMAD4-modulated gene profile predicts disease-free survival in stage II and III colorectal cancer

2020 ◽  
Author(s):  
Bryan C. Szeglin ◽  
Chao Wu ◽  
Michael R. Marco ◽  
Hyun Sung Park ◽  
Zeda Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Training Dataset ◽  
Validation Dataset ◽  
Gene Profile ◽  
Free Survival ◽  
Colorectal Cancer Patients ◽  
Disease Free

AbstractObjectiveLoss of SMAD4 is associated with worse outcomes for colorectal cancer patients. We used gene ontology and bioinformatics to identify an RNA-based SMAD4-modulated profile and test its association with patient outcome.DesignUsing a discovery dataset of 250 colorectal cancer patients, we analyzed expression of BMP/Wnt target genes for association with SMAD4 expression. Promoters of the BMP/Wnt genes were interrogated for SMAD-binding elements. 15 genes were implicated and three tested for modulation by SMAD4 in patient-derived colorectal cancer tumoroids. Expression of the 15 genes was used for unsupervised hierarchical clustering of a training dataset and two resulting clusters modeled in a centroid model. This model was applied to an independent validation dataset of stage II and III patients. Disease-free survival was analyzed by the Kaplan-Meier method.ResultsIn vitro analysis of three genes identified in the SMAD4-modulated profile (JAG1, TCF7, MYC) revealed modulation by SMAD4 consistent with the trend observed in the profile. In the training dataset (n = 553), the profile was not associated with outcome. However, among stage II and III patients (n = 461), distinct clusters were identified by unsupervised hierarchical clustering that were associated with disease-free survival (p = 0.02). The main model was applied to a validation dataset (n = 257) which confirmed the association of clustering with disease-free survival (p = 0.02).ConclusionsA SMAD4-modulated RNA-based gene profile identified high-risk stage II and III colorectal cancer patients, can predict disease-free survival, and has prognostic potential for stage II and III colorectal cancer patients.

Preoperative hepatic and regional arterial chemotherapy in the prevention of liver metastasis after colorectal cancer surgery

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4090-4090
Author(s):  
J. Xu ◽  
Y. Zhong ◽  
W. Niu ◽  
X. Qin ◽  
Y. Wei ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Overall Survival ◽  
Liver Metastasis ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Stage Iii ◽  
Control Group ◽  
Free Survival ◽  
Significant Difference ◽  
Disease Free

4090 Background: To investigate whether preoperative hepatic and regional arterial chemotherapy are able to prevent liver metastasis and improve overall survival in patients receiving curative colorectal cancer resection. Methods: Patients with Stage II or Stage III colorectal cancer (CRC) were randomly assigned to receive preoperative hepatic and regional arterial chemotherapy (PHRAC group, n=256) or surgery alone (control group, n=253). The primary endpoint was disease-free survival, whereas the secondary endpoints included liver metastasis-free survival and overall survival. Results: There were no significant differences in overall morbidity between PHRAC and Control groups. During the follow-up period (median, 42 months), the median liver metastasis time for patients with stage III CRC was significantly longer in the PHRAC group (16±3 months v.s. 8±1 months, P=0.01). In stage III patients, there was also significant difference between the two groups with regard to the incidence of liver metastasis (18.9% vs 27.3%, P=0.01), 5-year disease-free survival (70.2% vs 52.0%, P=0.0076), 5-year overall survival (80.3% vs 69.5%, P=0.020) and the median survival time (40.1± 4.6 months vs 36.3 ± 3.2 months, P=0.03). In the PHRAC arm, the risk ratio of recurrence was 0.63 (95% CI, 0.51–0.79, P=0.0001), of death was 0.50(95% CI, 0.32–0.67; P=0.005), and of liver metastasis was 0.70 (95% CI, 0.52–0.86; p=0.01). In contrast, PHRAC seemed to be no benefit for stage II patients. Toxicities, such as hepatic toxicity and leucocyte decreasing, were mild and could be cured with medicine. Conclusions: Preoperative hepatic and regional arterial chemotherapy, in combination with surgical resection, could be able to reduce and delay the occurrence of liver metastasis and therefore improve survival rate in patients with stage III colorectal cancer. No significant financial relationships to disclose.

Radiomic Signature-Based Nomogram to Predict Disease-Free Survival in Stage II and III Colon Cancer

2019 ◽  
Author(s):  
Xun Yao ◽  
Caixia Sun ◽  
Fei Xiong ◽  
Xinyu Zhang ◽  
Chao Wang ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Free Survival ◽  
Disease Free

The AST/ALT Ratio Is an Independent Prognostic Marker for Disease-free Survival in Stage II and III Colorectal Carcinoma

2021 ◽  
Vol 41 (1) ◽  
pp. 429-436
Author(s):  
LUKAS SCHEIPNER ◽  
MARIA ANNA SMOLLE ◽  
DOMINIK BARTH ◽  
FLORIAN POSCH ◽  
MICHAEL STOTZ ◽  
...  
Keyword(s):  
Colorectal Carcinoma ◽  
Prognostic Marker ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Free Survival ◽  
Independent Prognostic Marker ◽  
Disease Free

scholarly journals TRIM25 regulates oxaliplatin resistance in colorectal cancer by promoting EZH2 stability

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Sha Zhou ◽  
Jianhong Peng ◽  
Liuniu Xiao ◽  
Caixia Zhou ◽  
Yujing Fang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Disease Free Survival ◽  
Free Survival ◽  
Epigenetic Regulator ◽  
Crc Management ◽  
Disease Free ◽  
Resistance To Chemotherapy

AbstractResistance to chemotherapy remains the major cause of treatment failure in patients with colorectal cancer (CRC). Here, we identified TRIM25 as an epigenetic regulator of oxaliplatin (OXA) resistance in CRC. The level of TRIM25 in OXA-resistant patients who experienced recurrence during the follow-up period was significantly higher than in those who had no recurrence. Patients with high expression of TRIM25 had a significantly higher recurrence rate and worse disease-free survival than those with low TRIM25 expression. Downregulation of TRIM25 dramatically inhibited, while overexpression of TRIM25 increased, CRC cell survival after OXA treatment. In addition, TRIM25 promoted the stem cell properties of CRC cells both in vitro and in vivo. Importantly, we demonstrated that TRIM25 inhibited the binding of E3 ubiquitin ligase TRAF6 to EZH2, thus stabilizing and upregulating EZH2, and promoting OXA resistance. Our study contributes to a better understanding of OXA resistance and indicates that inhibitors against TRIM25 might be an excellent strategy for CRC management in clinical practice.

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