scholarly journals Tumour purity as a prognostic factor in colon cancer

2018 ◽  
Author(s):  
Yihao Mao ◽  
Qingyang Feng ◽  
Peng Zheng ◽  
Liangliang Yang ◽  
Tianyu Liu ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Prognostic Factor ◽  
Relative Proportion ◽  
Genetic Profile ◽  
M2 Macrophages ◽  
Negatively Associated ◽  
Transcriptomic Data ◽  
Mutation Burden ◽  
The Impact

AbstractTumour purity is defined as the proportion of cancer cells in the tumour tissue. The impact of tumour purity on colon cancer (CC) prognosis, genetic profile and microenvironment has not been thoroughly accessed. Therefore, clinical and transcriptomic data from three public datasets, GSE17536/17537, GSE39582, and TCGA were retrospectively collected (n = 1248). Tumour purity of each sample was inferred by a computational method based on transcriptomic data. Stage III and MMR-deficient (dMMR) CC patients showed a significantly lower tumour purity. Low purity CC conferred worse survival and tumour purity was identified as an independent prognostic factor. Moreover, high tumour purity CC patients benefited more from adjuvant chemotherapy. Subsequent genomic analysis found that the mutation burden was negatively associated with tumour purity with only APC and KRAS significantly more mutated in high purity CC. However, no somatic copy number alteration event was correlated with tumour purity. Furthermore, immune-related pathways and immunotherapy-associated markers (PD-1, PD-L1, CTLA-4, LAG-3, and TIM-3) were highly enriched in low purity samples. Notably, the relative proportion of M2 macrophages and neutrophils, which indicated worse survival in CC, was negatively associated with tumour purity. Therefore, tumour purity exhibited potential value for CC prognostic stratification as well as adjuvant chemotherapy benefit prediction. The relative worse survival in low purity CC may attribute to higher mutation frequency in key pathways and purity related microenvironmental changing.SummaryLow purity colon cancer patients conferred worse survival and benefited less from adjuvant chemotherapy. The mutation burden was negatively associated with tumour purity. Low purity samples exhibited intense immune phenotype with more M2 macrophages and neutrophils infiltration.

A National Cancer Database (NCDB) analysis of the impact of nonmetastatic colon cancer sidedness on survival.

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 139-139
Author(s):  
Deven Patel ◽  
Timothy DiPeri ◽  
Brian Cox ◽  
Andrew Eugene Hendifar ◽  
Arsen Osipov ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Logistic Regression ◽  
Adjuvant Chemotherapy ◽  
Large Population ◽  
Stage I ◽  
Prognostic Impact ◽  
Metastatic Colon Cancer ◽  
Prognostic Features ◽  
Binomial Logistic Regression ◽  
The Impact

139 Background: Differences in embryological origin and tumor biology distinguish right-sided colon cancer (RCC) from left-sided colon cancer (LCC). Previous studies characterizing the prognostic impact of colon cancer laterality on clinical outcomes in non-metastatic colon cancer have been conflicting, thus closer examination is needed. Methods: Using the NCDB, patients with stage I-III colon cancer between 2004-2014 were stratified according to tumor location; RCC vs. LCC. Patient (pt) and tumor characteristics were compared in univariate analysis, survival (OS) was estimated by Kaplan-Meier (KM) curves and Cox proportional hazards modeling. Binomial logistic regression analysis was utilized to identify variables associated with colon cancer laterality. Results: Of the 342,735 pts who met inclusion criteria, 210,343 (61.4%) were diagnosed with RCC, and 132,392 (38.6%) with LCC. Pts with RCC were older (mean 71.6 vs. 66.4 years, p< 0.001) and predominantly female (65% vs. 35%, p< 0.001) compared to those with LCC. A trend towards poorer OS was seen in pts with RCC (mean 91.0 mos [95% CI: 90.2-91.8]) compared to LCC (112.2 mos [95% CI: 110.9-113.6]) in unadjusted analysis. On Cox multivariable adjusted analyses there was a significant but minimal impact on OS and laterality (hazard ratio or HR [LCC as ref] 0.978, 95% CI 0.967-0.989 p< 0.0001). Multiple unadjusted KM survival analyses showed RCC with T4 disease, high-grade, LVI/PNI, positive margins, N0-N2 disease, tumor deposits, and receipt of adjuvant chemotherapy had poorer OS than those features in LCC (all p < 0.0001). Binomial logistic regression showed RCCs were significantly more likely to be higher grade (odds ratio or OR 2.024) and MSI-H (OR 2.010) with trends (nonsignificant) towards more likely having N1-2 positive disease, LVI, less receipt of adjuvant chemotherapy, and fewer tumor deposits. Conclusions: The impact of sidedness on prognosis in stage I-III colon cancer is complex. In this large, population-based study, RCC tends to be associated with more adverse prognostic features than LCC. More investigation into the biologic differences between RCC and LCC is warranted and how they impact phenotype and survival.

scholarly journals P-151 The impact of adjuvant chemotherapy regimens in stage II colon cancer (CC) patients

2020 ◽  
Vol 31 ◽  
pp. S139
Author(s):  
S. Lobo-Martins ◽  
M. Martins ◽  
P. Semedo ◽  
C. Alvim ◽  
H. Luna Pais ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Stage Ii ◽  
Stage Ii Colon Cancer ◽  
The Impact

Uptake of adjuvant chemotherapy for colon cancer in older and younger patients in the Irish population.

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 478-478
Author(s):  
Seamus Coyle ◽  
Zia Rehman ◽  
Chalen Lee ◽  
Sandra Deady ◽  
Harry Comber ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Clinical Practice ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Older Patients ◽  
The Elderly ◽  
Stage Ii ◽  
Stage Iii ◽  
Younger Patients ◽  
The Impact

478 Background: Colon cancer is predominantly a disease of the elderly, with recent evidence supporting the use of adjuvant chemotherapy in the older population. However, it remains unclear to what degree such patients are receiving adjuvant therapy in clinical practice. We examined uptake of adjuvantchemotherapy and it’s impact on survival in older patients with stage II and stage III colon cancer in a national cohort. Methods: Using the National cancer Registry of Ireland, we identified 3,486 patients with stage II and III colon cancer who were treated with curative resection from 2004-2009. Clinopathological features and chemotherapy use were compared between those ≥70 years and those < 70 years. Results: A total of 2,026 patients with stage II disease were identified, 56% male and 60% ≥ 70 years. T3 tumors accounted for 81%, T4 19% and 89% were grade 2/3. Adjuvant chemotherapy was utilized in 10% and 40% of ≥ 70 and <70 years, respectively (p<0.0001). A benefit for chemotherapy over observation alone was seen in both the older [HR 0.36; 95% CI 0.36 – 0.68; p <0.0001] and younger patient groups [HR 0.43; 95% CI 0.2701 - 0.6881; p<0.0004]. Of 1,460 patients with stage III disease, 51% were ≥ 70 years, 54% male. 34% of older and 83% of younger patients received adjuvant therapy (p<0.0001). A similar magnitude of benefit from chemotherapy compared to observation was seen in patients ≥ 70 years [HR 0.30; 95% CI 0.29 - 0.45 ; p <0.0001] and <70 years [HR 0.22 95%CI 0.1 – 0.2; p<0.0001] with stage III disease. Conclusions: Adoption of adjuvant chemotherapy appears to be associated with significant survival benefit in older patients (age ≥ 70 years), however, is still underutilized in clinical practice. The impact of sociodemographic and clinicopathological features as potential drivers of treatment decisions in a cohort of this population will be reported.

Gender differences in prognostic value of immune-related biomarkers in colon cancer patients randomized to surgery or surgery and adjuvant chemotherapy treatment.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 3603-3603
Author(s):  
Lisa Villabona ◽  
Giuseppe V. Masucci ◽  
Peter Ragnhammar
Keyword(s):  
Ovarian Cancer ◽  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Mhc Class I ◽  
Class I ◽  
Lymphocyte Infiltration ◽  
Hla Type ◽  
Male Patients

3603 Background: HLA-A*02, a common allele in the Scandinavian population, is a negative prognostic factor in epithelial ovarian cancer. It is a strong predictor of patient outcome, only inferior to clinical staging. This prognostic trait in epithelial ovarian cancer is stronger by the presence of the gene compared with the expression of its protein, MHC class I. Microsatellite instability (MSI) is used as a biomarker for prognosis and is suggested an increased tumor mutational burden which can make the tumor more susceptible for T cell mediated immunotherapy. Our aim was to analyze the prognostic markers HLA-A*02 genotype, MHC class I on tumor cells, the CD8+ lymphocyte infiltration and MSI status in colon cancer patients with randomized treatment. Methods: Clinical information and primary tumors were collected from 520 colon cancer patients and followed for overall survival for 120 months. Patients hade stage II and III colon cancer and were randomized to surgery alone or surgery and adjuvant chemotherapy. HLA-A*02 genotype was determined by conventional PCR. MHC class I, MSI status and CD8+ lymphocyte infiltration were determined by immunohistochemistry. Results: Female patients with a stage III tumor and HLA-A*02 genotype had a better outcome if they had received adjuvant chemotherapy instead of just surgery (p = 0.03), whereas this was not the case for patients with other HLA-A genotypes or in the male patients where HLA-type did not correlate to outcome. MHC class I expression did not act as a prognostic factor, however the presence of CD8+ lymphocytes in the invasive margin and inside the tumor was a positive prognostic factor for overall survival (p = 0.01), although only statistically significant in the male patients (p = 0.03). 21% patients had a tumor with MSI (23% of the female and 19% of the male patients respectively). MSI tumors had a slightly better outcome and this was irrespective of gender and HLA-type. Conclusions: The prognostic traits of HLA-A*02 appear in this colon cancer cohort to act differently in male and female patients. Also CD8+ infiltration is different between genders. These findings suggest that men and women may have two different immune responses to malignancy.

A novel interaction of genotype, gender, and adjuvant treatment in survival after resection of stage III colon cancer: Results of CALGB 89803.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 452-452
Author(s):  
Chloe Evelyn Atreya ◽  
Robert S. Warren ◽  
Donna Niedzwiecki ◽  
Robert J. Mayer ◽  
Richard M. Goldberg ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Phase Iii ◽  
Zinc Binding ◽  
Stage Iii ◽  
P53 Mutations ◽  
Stage Iii Colon Cancer ◽  
Mutational Status ◽  
The Impact

452 Background: The p53 tumor suppressor gene is frequently mutated in colorectal cancer, but reports on the effect of p53 mutations on response to adjuvant chemotherapy and survival are inconclusive. This study investigates whether p53 mutational status (wild-type, zinc or non-zinc binding mutations) impacts survival following adjuvant therapy containing fluorouracil/leucovorin with or without irinotecan (5FU/LV or IFL) in women and men with stage III colon cancer. Methods: As part of a retrospective analysis of prospectively accrued data, p53 mutational status was determined for 609 patients with stage III colon cancer who were randomized on CALGB 89803, a phase III adjuvant chemotherapy trial. p53 exons 5-8 were analyzed by direct sequencing or sequencing by hybridization. p53 mutations were identified in 276 tumors (45%), of which 134 were in the zinc binding and 142 were in the non-zinc binding regions of the core domain. Cox regression was used to study the impact of p53 mutational status, sex, and adjuvant chemotherapy on disease-free (DFS) and overall survival (OS). Results: p53 mutational status did not predict differential survival or response to adjuvant therapy among the 609 patients assessed. However, a significant sex by treatment interaction was observed for both DFS (Pinteraction=0.008) and OS (Pinteraction=0.002). Significant differences in DFS by p53 mutational status were observed among women (logrank P = 0.009). No such differences were observed among men (logrank P = 0.33). Similar results were observed for OS. There was marginal evidence of a treatment-related impact on the interaction between sex and p53 mutational status for both DFS and OS (DFS Pinteraction = 0.07; OS Pinteraction = 0.11). There was a trend toward improved OS when women with zinc binding mutations received IFL versus 5FU/LV (P = 0.08) and toward worse DFS when women with non-zinc binding mutations were treated with IFL versus 5FU/LV (P =0.08). Conclusions: This exploratory subset analysis suggests that p53 mutational status may be used to predict prognosis in a sex- and potentially chemotherapeutic regimen-specific manner.

A retrospective analysis on the impact of preoperative neutrophil to lymphocyte ratio in stage II colon cancer.

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 794-794
Author(s):  
Deepna Jaiswal ◽  
Suparna Mantha ◽  
Lucas Wong ◽  
Luis Seija ◽  
Yolanda Munoz
Keyword(s):  
Colon Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Critical Role ◽  
Univariate Analysis ◽  
Neutrophil To Lymphocyte Ratio ◽  
Stage Ii ◽  
Lymphocyte Ratio ◽  
Stage Ii Colon Cancer ◽  
The Impact

794 Background: Inflammation has a critical role in tumor genesis and progression of cancer. The neutrophil to lymphocyte ratio (NLR) is an indication of balance between the immune systems pro and defense mechanism against cancer. Elevated NLR is of interest in many cancers, including colon cancer. Although surgery is the mainstay of treatment for early stage colon cancer, adjuvant chemotherapy for stage II colon cancer has remained debatable. We proposed to study the impact of the NLR in patients with stage II colon cancer and to identify high risk patients who would benefit from adjuvant chemotherapy. Methods: Three hundred and eighty patients diagnosed with Stage II colon cancer at our institution were included in this retrospective study. Kaplan-Meir curves and multivariate Cox-regression analyses were calculated for overall survival. Results: Univariate analysis showed NLR was not statistically significant as predictor of mortality (p-value=0.0857). However, after adjusting for recurrence, chemotherapy, age, white blood cell count, the NLR was predictive for survival, with a hazard ratio of 1.05 and 95% confidence interval of (1.006 - 1.1). Recurrence and age were also significant predictors of survival (p-values of <0.0001 for both), and HR of 3.1 (2.0 – 4.6) and 1.4 (1.2 – 1.5), respectively. Conclusions: The neutrophil to lymphocyte ratio might be an independent prognostic marker for overall survival in stage II colon cancer patients. Given the retrospective nature of our study, further studies are indicated to confirm our findings.

scholarly journals The impact of chronic illnesses on the use and effectiveness of adjuvant chemotherapy for colon cancer

Cancer ◽  
2007 ◽  
Vol 109 (12) ◽  
pp. 2410-2419 ◽  
Author(s):  
Cary P. Gross ◽  
Gail J. McAvay ◽  
Zhenchao Guo ◽  
Mary E. Tinetti
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Chronic Illnesses ◽  
The Impact

scholarly journals The Impact of Metastatic Lymph Node Size on Long-Term Outcomes Following Curative Colectomy for Pathological Stage III Colon Cancer

2021 ◽  
Author(s):  
Chikara Maeda ◽  
Yusuke Yamaoka ◽  
Akio Shiomi ◽  
Hiroyasu Kagawa ◽  
Hitoshi Hino ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Multivariate Analysis ◽  
Lymph Node ◽  
Adjuvant Chemotherapy ◽  
Metastatic Lymph Node ◽  
Long Term Outcomes ◽  
Stage Iii Colon Cancer ◽  
The Impact ◽  
Group D

Abstract Background: In node-positive colon cancer, the impact of MLN size on prognosis is controversial. The aim of this study was to clarify the impact of metastatic lymph node (MLN) size on long-term outcomes in patients undergoing curative resection for pStage III colon cancer.Methods: This study enrolled patients who underwent curative colectomy for pStage III colon cancer between January 2013 and December 2015. All eligible patients were divided into four groups based on the short-axis diameter of the largest MLN: Group A, < 5 mm; Group B, ≥ 5 mm and < 10 mm; Group C, ≥ 10 mm and < 15 mm; and Group D, ≥ 15 mm. We performed univariate and multivariate analysis using Cox proportional hazard regression models to identify clinicopathological factors affecting recurrence-free survival (RFS).Results: A total of 209 patients were analyzed. We evaluated 7305 LNs, of which 644 were metastatic. The 5-year RFS rates of Groups A, B, C, and D were 82.3%, 74.6%, 74.5%, and 60.7%, respectively. In univariate analysis, age older than 70 years, Group D (largest MLN ≥ 15 mm), and the absence of adjuvant chemotherapy were significantly associated with RFS. In multivariate analysis, Group D (hazard ratio [HR], 3.95; 95% confidence interval [CI], 1.34–11.65; p=0.01) and the absence of adjuvant chemotherapy (HR, 2.44; 95% CI, 1.26-4.72; p<0.01) were independently associated with worse RFS.Conclusion: A maximum MLN ≥ 15 mm was significantly associated with worse RFS in stage III colon cancer. Bulky MLNs might be a poor prognostic factor in node-positive colon cancer.

scholarly journals UCHL1 Promotes Chemoresistance to 5-Fluoruracil Based Adjuvant Chemotherapy and is a Prognostic Marker for Stage II Colon Cancer Patients

2021 ◽  
Author(s):  
Liyuan Ma ◽  
Chaowen Wu ◽  
Lu Ding ◽  
Dong Yu ◽  
Xinrong Shi ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Independent Prognostic Factor ◽  
Stage Ii ◽  
Cytotoxicity Test ◽  
Down Regulation ◽  
Stage Ii Colon Cancer

Abstract Background: 5-Fluoruracil based adjuvant chemotherapy after radical resection is recommended for stage II colon cancer patients with high risk of recurrence. Up to now, novel biomarkers still needed for better stratification for improving prognosis. Methods: Here we report that UCHL1 is an independent prognostic factor for stage II colon cancer patients and promotes chemoresistance both in vitro and in vivo. Results: Our study indicated that UCHL1 is significant up regulated in 96 pairs of stage II colon cancer patients who received postoperative 5-FU based chemotherapy. Stage II colon cancer patients with high UCHL1 expression showed high recurrence rate after chemotherapy. Multivariate Cox regression analysis showed that UCHL1 is an independent prognostic factor for overall survival (P=0.008) and disease-free survival (P=0.001). 5-FU based chemoresistance is examined in colon cancer cell lines (RKO and LoVo) with down regulation of UCHL1 by cytotoxicity test. Down regulation of UCHL1 exhibited decreased cell viability, elevated cell apoptosis rate, increased G2/M-phase and elevated level of cleaved caspase 3 and PARP when treated with 5-FU. Furthermore, the results in xenograft model are consistent with results in vitro.Conclusions: UCHL1 potentially contributing to identify recurrence risk and predict the benefit for postoperative 5-FU based adjuvant chemotherapy in stage II colon cancer patients.

Sign in / Sign up

Export Citation Format

Share Document