Treatment of colorectal cancer in Armenia: A retrospective hospital-based study from a developing world.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16099-e16099
Author(s):  
Samvel Bardakhchyan ◽  
Sergo Mkhitaryan ◽  
Davit Zohrabyan ◽  
Liana Safaryan ◽  
Armen Avagyan ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Median Survival ◽  
Cox Regression ◽  
Survival Rates ◽  
Disease Free Survival ◽  
Rectum Cancer ◽  
Cox Regression Analysis ◽  
Stage 4 ◽  
Significant Difference

e16099 Background: In Armenia colorectal cancer (CRC) is on the third place by incidence. Every year around 700 new cases are diagnosed with 60% diagnosed in 3rd and 4th stages. Methods: For this retrospective hospital-based study we have collected data from two main oncology centers in Armenia: National Oncology Center and Muratsan Hospital Complex of Yerevan state medical university. The information about patients with CRC who were treated at these two centers during 01/01/2010 - 07/01/2018 period was collected from the medical records. Results: 602 patients with CRC treated during mentioned period in these two hospitals were involved in final analysis. From them 51.8% were female. Median age at diagnosis was 58. Median follow up time was 37 months (range 3-207). 26.1% had right sided, 30.9% left sided and 43.0% rectum cancer. 8.6% of patients had stage 1, 32.9% stage 2, 38.0% stage 3, 17.6% stage 4 CRC and for 2.7% patients stage was unknown. The median survival was not reached for the entire cohort ( > 37 months). Median survival was > 66.5 months for 1st, > 48.5 months for 2nd, > 35 months for 3rd and 19 months for 4th stages. Tumor stage, grade and histology were the main independent prognostic factors by univariate and multivariate Cox regression analysis. For stage 2 CRC patients (198) we found significant difference regarding overall survival (OS) (p = 0.024) and disease free survival (DFS) (p = 0.006) for those who received adjuvant chemotherapy after surgery compared to those who didn’t receive adjuvant chemotherapy. For stage 2 and 3 rectum cancer patients, our study failed to show OS (2nd stage: p = 0.961; 3rd stage: p = 0.348) or DFS (2nd stage: p = 0.719; 3rd stage: p = 0.983) advantage for those who received radiotherapy (RT) compared with those who didn’t receive RT. In our study population 28.3% of stage 4 patients received chemotherapy combined with Bevacizumab while 70% were treated with chemotherapy only. Median OS between these two groups wasn’t significantly different (21 months in Chemo+Bevacizumab group and 18.5 months in chemo only group (p = 0.382)). 3 and 5-year survival rates were 62.9% and 51.8% for all stages combined and 79.7% and 68.5% for stages 1-2, 62.5% and 48.4% for stage 3, 24.4% and 17% for stage 4 respectively. Conclusions: As seen from our results our survival rates are inferior compared to that of developed world. The reasons for that could be compromise in surgery and RT, poor pathological assessment, unavailability of some molecular markers, poor availability of new targeted drugs and absence of national treatment guidelines.

Thrombocytosis as a predictor of poor prognosis in colorectal cancer patients.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 540-540
Author(s):  
Ravi Ramjeesingh ◽  
Amie Jones ◽  
Christine Orr ◽  
Corey Sean Bricks ◽  
Wilma M Hopman ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Platelet Count ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Retrospective Chart Review ◽  
Cancer Center ◽  
Cox Regression Analysis ◽  
Survival Difference ◽  
Stage 4 ◽  
Significant Difference

540 Background: Thrombocytosis has been identified as a prognostic factor in many cancer types including ovarian, breast, and lung cancers. In colorectal cancer (CRC), the literature is divided. Several smaller case studies suggest a negative prognosis in CRC patients with pre-operative thrombocytosis, a larger population study contradicts this. Methods: We performed a retrospective chart review of CRC patients treated at the Cancer Center of Southeastern Ontario diagnosed from January 2005 to December 2011. 1304 confirmed CRC patient charts were identified and patient, tumor, blood work and treatment variables were extracted. Results: 1,096 patients had platelet count available at the time of oncology consult. 222 (20.3%) were characterized as having thrombocytosis (>400x109/L). No difference was identified between those with normal and with thrombocytosis with regards to age, sex, comorbidities, and BMI. However, a statistically significant difference was identified when looking at several pathological characteristics. Significantly more patients with thrombocytosis presented with stage 4 disease (p<0.0001). Additionally less early T-stage (T1: p<0.05, T2: p<0.001), lymph node positivity (p<0.05) and LVI (p<0.05) was identified. Univariate analysis identified a significant difference in survival (1yr: 71.6% vs 88.1%, p<0.0001; 2 yr: 58.1% vs 78.1%, p<0.0001; 5yr: 48.2% vs 64.7%, p<0.0001). Multivariate Cox regression analysis, identified a statistically significant effect of thrombocytosis on risk of dying (HR=1.434, C.I 1.153-1.784, p=0.001). A survival difference was primarily identified in the Stage 4 population (1yr: 55.8% with thrombocytosis vs 72.9% with normal platelet count, p=0.0058; 2 yr: 36.0% vs 50.2%, p=0.0388; 5yr: 26.7% vs 32.0%, p=0.4042). There were no differences in the number of metastatic sites or the number of days on chemotherapy to account for the survival difference. Conclusions: Thrombocytosis, at the time of oncology consultation appears to predict a lower chance of survival in CRC patients, especially in the stage 4 population. Further work is required to elucidate the mechanism of action between elevated platelet counts and survival.

scholarly journals Serum Concentration of Genistein, Luteolin and Colorectal Cancer Prognosis

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 600 ◽  
Author(s):  
Ruijingfang Jiang ◽  
Gernot Poschet ◽  
Robert Owen ◽  
Muhabbet Celik ◽  
Lina Jansen ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Serum Concentration ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Ultra Performance Liquid Chromatography ◽  
Population Based ◽  
Potential Interaction ◽  
Cancer Prognosis ◽  
Cox Regression Analysis

Although flavonoid phytoestrogens have been suggested to be associated with reduced risk of colorectal cancer (CRC), their influence on CRC prognosis remains uncertain. A population-based cohort of 2051 patients diagnosed with stage I–III CRC in southwest Germany in 2003–2010 were followed for five years. Post-diagnostic serum concentration of genistein and luteolin were measured using Ultra-Performance Liquid Chromatography with mass spectrometry. Multivariable Cox regression analysis was conducted to calculate the Hazard Ratios (HRs) and 95% confidence interval (CI) for the association between flavonoids concentration and overall morality, CRC-specific mortality, CRC recurrence, and disease-free survival (DFS). Median (interquartile range) serum concentration of genistein and luteolin was 11.90 ng/µL (10.08–14.13) and 7.20 ng/µL (6.40–8.16), respectively. Neither serum genistein nor luteolin was associated with CRC prognosis. There was no clear evidence of departure from linearity. However, the association might be differential by adjuvant chemotherapy. Associations pointed towards lower risk in patients who received chemotherapy and higher risk in those without chemotherapy for overall mortality regarding serum genistein (P-interaction = 0.02) and correspondingly for CRC recurrence (P-interaction: 0.03) and DFS (P-interaction: 0.01) with respect to luteolin. Our study provides little evidence that serum genistein and luteolin are associated with colorectal cancer prognosis. Future studies are warranted to evaluate the potential interaction with adjuvant chemotherapy.

Prognostic role of aberrant mTOR activation in patients with stage II and III colorectal cancer

2020 ◽  
Vol 14 (12) ◽  
pp. 1127-1137
Author(s):  
Tong-Tong Zhang ◽  
Yi-Qing Zhu ◽  
Hong-Qing Cai ◽  
Jun-Wen Zheng ◽  
Jia-Jie Hao ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cox Regression ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Poor Prognostic Factor ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Potential Biomarker ◽  
Risk Predictor

Aim: This study aimed to develop an effective risk predictor for patients with stage II and III colorectal cancer (CRC). Materials & methods: The prognostic value of p-mTOR (Ser2448) levels was analyzed using Kaplan–Meier survival analysis and Cox regression analysis. Results: The levels of p-mTOR were increased in CRC specimens and significantly correlated with poor prognosis in patients with stage II and III CRC. Notably, the p-mTOR level was an independent poor prognostic factor for disease-free survival and overall survival in stage II CRC. Conclusion: Aberrant mTOR activation was significantly associated with the risk of recurrence or death in patients with stage II and III CRC, thus this activated proteins that may serve as a potential biomarker for high-risk CRC.

scholarly journals Differences in the outcomes of adjuvant chemotherapy for colon cancer prescribed by physicians in different disciplines: a population-based study in Taiwan

BMJ Open ◽  
2018 ◽  
Vol 8 (12) ◽  
pp. e021341
Author(s):  
Cheng-I Hsieh ◽  
Raymond Nien-Chen Kuo ◽  
Chun-Chieh Liang ◽  
Hsin-Yun Tsai ◽  
Kuo-Piao Chung
Keyword(s):  
Colon Cancer ◽  
Adjuvant Chemotherapy ◽  
Cox Regression ◽  
Surgical Margin ◽  
Disease Free Survival ◽  
Disease Stage ◽  
Multiple Primary Cancers ◽  
Positive Surgical Margin ◽  
Recurrence Rates ◽  
Significant Difference

ObjectivesOne feature unique to the Taiwanese healthcare system is the ability of physicians other than oncologists to prescribe systemic chemotherapy. This study investigated whether the care paths implemented by oncologists and non-oncologists differ with regard to patient outcomes.SettingData from the Taiwan Cancer Registry and National Health Insurance Database were linked to identify patients with colon cancer who underwent colectomy as first treatment within 3 months of diagnosis and adjuvant chemotherapy between 2005 and 2009.Participants and methodsPostoperative patients who underwent adjuvant chemotherapy were included in this study. The exclusion criteria included patients with stage IV disease, a positive surgical margin and early disease recurrence. Among the patients presenting with multiple primary cancers, we also excluded patients who were diagnosed with colon cancer but for whom this was not the first primary cancer. The variables included sex, age, comorbidities, disease stage, chemotherapy cycle and changes in treatment regimen as well as the specialty of treatment providers and their case volume. Cox regression models and Kaplan-Meier analysis were used to examine differences in outcomes in the matched cohorts.ResultsWe examined 3534 patients who were prescribed adjuvant chemotherapy by physicians from different disciplines. In terms of 5-year disease-free survival, no significant difference was observed between the groups of oncologists or surgeons among patients with stage II (90.02%vs88.99%) or stage III (77.64%vs79.99%) diseases. Patients who were subjected to changes in their chemotherapy regimens presented recurrence rates higher than those who were not.ConclusionsThe discipline of practitioners is seldom taken into account in most series. This is the first study to provide empirical evidence demonstrating that the outcomes of patients with colon cancer do not depend on the treatment path, as long as the selection criteria for adjuvant chemotherapy is appropriate. Further study will be required before making any further conclusions.

scholarly journals Outcomes of Relapsed/Refractory Patients with IDH1/2 Mutated AML Treated with Non-Targeted Therapy: Results from the NCRI AML Trials

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 664-664 ◽  
Author(s):  
Robert K. Hills ◽  
Rosemary Gale ◽  
David C. Linch ◽  
Brian J.P Huntly ◽  
Elli Papaemmanuil ◽  
...  
Keyword(s):  
Median Survival ◽  
Large Scale ◽  
Cox Regression ◽  
Remission Rate ◽  
Secondary Outcome ◽  
Cox Regression Analysis ◽  
Post Transplant ◽  
Significant Difference ◽  
The Uk ◽  
Idh2 Mutation

Abstract Introduction: The increasing delineation of acute myeloid leukemia (AML) has identified a number of genetic mutations which may be amenable to targeted therapies. However, such mutations typically only occur in a minority of patients, and this relative paucity presents challenges in drug development. Even for more common mutations such as FLT3 ITD, randomised trials can take many years to complete, and there is the issue of how to deal with patients who are tested but not eligible. Earlier phase trials therefore tend to be single arm studies, and often recruit in the relapsed/refractory population, where eligibility is known up front, and it is possible to obtain an early read out for efficacy. Such is the case for the recent evaluations of enasidenib and ivosidenib in IDH1/2 mutated patients. However, with single-arm studies there a need to contextualise results. We therefore looked at outcomes from the United Kingdom NCRI trials of AML for patients with IDH1/IDH2 mutations who were relapsed or refractory to therapy. Methods: A database search identified patients within the UK NCRI AML trials with an IDH1/IDH2 mutation, who had received intensive induction and who were either: in second relapse, relapsed post-transplant, refractory to two courses of induction, or who relapsed within 1 year of remission. Outcomes were measured from the point of eligibility: patients who were multiply eligible were included only once, at their first point of eligibility. The primary outcome was overall survival, with achievement of complete remission, with or without peripheral count recovery, as secondary outcome. Cox regression analysis was used to identify prognostic factors within the cohort of patients. Cytogenetics are evaluated using the MRC classification. Results: A total of 757 patients were identified with IDH1/2 mutation (IDH1 alone n=247; IDH2 alone n=504, both n=6). Of these 211 patients satisfied the relapsed/refractory criteria (IDH1 alone n=81; IDH2 alone n=128; both IDH1/2 n=2; refractory n=28; relapsed post SCT n=34; relapsed within 1 year with no SCT n=138; second relapse n=11 - Table). Median age was 54 years (range 22-77); 51% were male; and 95% of patients had intermediate risk cytogenetics. Remissions were achieved in 43/211 patients (20%; refractory 50%; relapsed post SCT 15%; relapsed within 1 year 17%; second relapse 9% - Table). Patients with IDH1 mutations had a remission rate of 23%; for IDH2 mutated patients, the rate was 18%. Median survival was 4.4 months for IDH1 mutated patients, and 6.6 months for IDH2 mutations; 2 year survival was 17%, 21% respectively. Split by age, median survival was 4.0 and 9.4 months respectively (2-year survival 19%; 27%) for patients aged <60; in patients aged 60 or over, median survival was 5.2, 2.9 months (2 year survival 13%; 8%). In multivariable analyses no presenting factor was significantly associated with survival among IDH1 patients. In particular, there was no significant difference in survival by age or between the four different eligibility groups. By contrast, among IDH2 patients, patients in second relapse had worst survival, followed by those relapsing post transplant, those relapsing within 1 year, and those with disease refractory to two courses of therapy (p=0.001); older patients had significantly worse survival (p=0.004 for age older or younger than 60). Conclusions: These results give context to the recent findings in single arm studies of ivosidenib for relapsed/refractory IDH1 mutated patients, and enasidenib for patients harbouring an IDH2 mutation. In the two studies reported, median survival was respectively 8.8 and 9.3 months, compared to 4.4 and 6.6 months in a younger group of patients identified from the UK NCRI AML trials treated with a variety of therapies. In both monotherapy trials the median survival was extended: however, reported one-year survival was not greatly improved (enasidenib 1 year survival 39% vs 34% for the NCRI cohort; ivosidenib, approximately 35% vs 32%). The difference in survival for IDH2 mutated patients in the NCRI cohort, by age and route to eligibility indicates that the interpretation of the results of single arm studies, in a heterogeneous condition such as AML, is fraught with difficulties. Ideally the magnitude of benefit should be assessed using randomised data from large scale collaborations and platform trials. Table: Outcomes for IDH1/IDH2 mutated relapsed/refractory patients in the UK NCRI AML trials. Disclosures Hills: Daiichi Sankyo: Consultancy, Honoraria. Russell:Daiichi Sankyo: Consultancy; Jazz Pharma: Speakers Bureau; Pfizer: Consultancy, Honoraria, Speakers Bureau.

Can red cell distribution width and hemoglobin level variations be utilized to predict the prognosis of Stage III operative colorectal cancer patients with adjuvant chemotherapy treatment?

2020 ◽  
Author(s):  
Jie Li ◽  
Yuan-Yi Rui ◽  
Bo Song ◽  
Ke Zhang ◽  
Bo Yi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Cancer Patients ◽  
Cox Regression ◽  
Stage Iii ◽  
Red Cell ◽  
Cell Distribution ◽  
Distribution Width ◽  
Cox Regression Analysis ◽  
Colorectal Cancer Patients

Abstract Background: The aim of this study was to find that if the red cell distribution width (RDW) or hemoglobin (Hb) level variations had prognostic value in stage III colorectal cancer patients treated with operation and adjuvant chemotherapy. Methods: One hundred and twenty-two patients were included in this retrospective study. All were diagnosed and re-staged as stage III colorectal cancer in Sichuan Cancer Hospital according to the AJCC Cancer Staging Manual, 8 th edition, 2018. The patients received R0 resection before adjuvant chemotherapy. The baseline information, routine blood examination data, pathological outcome and prognostic stature was retracted from the database. Receiver operating characteristic (ROC) curve analysis was utilized to determine the cut-off value, while the survival analyses were performed with Kaplan-Meier curve, the log-rank test and the Cox regression analysis. Results: The chemotherapy-associated hemoglobin change (change between the pre- and post-chemotherapy hemoglobin levels) was identified to be associated with the metastasis (P=0.030). The optimal cut-off point was calculated to be -9.5 by the ROC curve of the hemoglobin change, while the area under the curve was 0.648 (95% CI: 0.524-0.772). The results showed that patients with larger hemoglobin decrease had significantly worse disease free survival (DFS) than those with smaller decrease (P=0.020). Factors associated with DFS in uni-variate COX regression analysis were the number of harvested lymph nodes (P=0.040) and the perineural invasion (P=0.020). The peri-chemotherapy change of hemoglobin level was estimated to have significant effect on patient survival (P=0.010). Conclusions: We concluded that chemotherapy-associated Hb change (change between the pre- and post-chemotherapy) was a DFS prognostic factor for the stage III colorectal cancer patients who underwent operation and adjuvant chemotherapy.

scholarly journals An Oxidative Stress Index-Based Score for Prognostic Prediction in Colorectal Cancer Patients Undergoing Surgery

2021 ◽  
Vol 2021 ◽  
pp. 1-15
Author(s):  
Yinghao Cao ◽  
Shenghe Deng ◽  
Lizhao Yan ◽  
Junnan Gu ◽  
Fuwei Mao ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Colorectal Cancer ◽  
Prediction Models ◽  
Cox Regression ◽  
Prognostic Index ◽  
Disease Free Survival ◽  
Tnm Stage ◽  
Cox Regression Analysis ◽  
T Stage ◽  
Prognostic Prediction

Oxidative stress plays an important role in the development of colorectal cancer (CRC). This study is aimed at developing and validating a novel scoring system, based on oxidative stress indexes, for prognostic prediction in CRC patients. A retrospective analysis of 1422 CRC patients who underwent surgical resection between January 2013 and December 2017 was performed. These patients were randomly assigned to the training set ( n = 1022 ) or the validation set ( n = 400 ). Cox regression model was used to analyze the laboratory parameters. The CRC-Integrated Oxidative Stress Score (CIOSS) was developed from albumin (ALB), direct bilirubin (DBIL), and blood urea nitrogen (BUN), which were significantly associated with survival in CRC patients. Furthermore, a survival nomogram was generated by combining the CIOSS with other beneficial clinical characteristics. The CIOSS generated was as follows: 0.074 × albumin (g/L), − 0.094 × bilirubin (μmol/L), and - 0.099 × blood   urea   nitrogen (mmol/L), based on the multivariable Cox regression analysis. Using 50% (0.1025) and 85% (0.481) of CIOSS as cutoff values, three prognostically distinct groups were formed. Patients with high CIOSS experienced worse overall survival (OS) ( hazard   ratio   HR = 4.33 ; 95% confidence interval [CI], 2.80-6.68; P < 0.001 ) and worse disease-free survival (DFS) ( HR = 3.02 ; 95% CI, 1.96-4.64; P < 0.001 ) compared to those with low CIOSS. This predictive nomogram had good calibration and discrimination. ROC analyses showed that the CIOSS possessed excellent performance ( AUC = 0.818 ) in predicting DFS. The AUC of the OS nomogram based on CIOSS, TNM stage, T stage, and chemotherapy was 0.812, while that of the DFS nomogram based on CIOSS, T stage, and TNM stage was 0.855. Decision curve analysis showed that these two prediction models were clinically useful. CIOSS is a CRC-specific prognostic index based on the combination of available oxidative stress indexes. High CIOSS is a powerful indicator of poor prognosis. The CIOSS also showed better predictive performance compared to TNM stage in CRC patients.

Adjuvant chemotherapy of cisplatin, 5-fluorouracil (5-FU) plus leucovorin (LV) for esophageal cancer: A case-matched cohort study in east china

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 15135-15135
Author(s):  
J. Zhang ◽  
J. Xiang ◽  
Y. Zhang ◽  
X. Zhou
Keyword(s):  
Esophageal Cancer ◽  
Adjuvant Chemotherapy ◽  
Randomized Clinical Trials ◽  
Cox Regression ◽  
Univariate Analysis ◽  
Disease Free Survival ◽  
Treatment Result ◽  
Chemotherapy Group ◽  
Study Results ◽  
Significant Difference

15135 Background: There are very few prospective randomized clinical trials regarding the adjuvant chemotherapy of esophageal cancer. This study is to compare the survival between the patients who received adjuvant chemotherapy of cisplatin, 5-Fluorouracil (5-FU) plus leucovorin (LV) and those who did not. Methods: Between 1998 and 2004, 90 esophageal cancer patients with adjuvant chemotherapy, and clinic-pathologically well- matched 180 patients without chemotherapy, were included in this study. Results: There was no significant difference for disease-free-survival and overall-survival in stage I (P=0.59&p=0.59), stage II (P=0.2778&P=0.2778) and stage III patients (P=0.695 &P=0.8667) between observation group and chemotherapy group. Chemotherapy was most effective for the patients who had metastasis in cervical and /or celiac lymph node (IVa subgroup) by both univariate analysis and multivariate COX regression model. 1 and 3-year DFS and OS are significantly better than those who did not receive the chemotherapy(P= 0.038,and 0.01, respectively). Among the factors evaluated by immunohistochemical staining, Bcl-2 expression in the primary tumor was a worse prognostic factor, and was more predictive in adjuvant chemotherapy group than no chemotherapy group. Conclusions: Adjuvant chemotherapy significantly improved the treatment result of stage IVa patients. Bcl-2 could be potentially used to analyze the prognosis and guild the adjuvant treatment in esophageal cancer. No significant financial relationships to disclose.

Exploring fingerprint ctDNA as a stratifying factor in colorectal cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16101-e16101
Author(s):  
Wending Sun ◽  
Jianwei Zhang ◽  
Jinwang Wei ◽  
Chun Dai ◽  
Jun Liu ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Adjuvant Chemotherapy ◽  
Early Stage ◽  
Disease Free Survival ◽  
Predictive Biomarker ◽  
Clinical Decision ◽  
Circulating Tumor Dna ◽  
Good Prognosis ◽  
Gene Copy ◽  
Significant Difference

e16101 Background: Colorectal cancer (CRC) ranks near the top in tumor-related deaths. Its standard-of-care is surgical resection plus adjuvant chemotherapy, which can extend patient’s live and disease-free survival for up to several years. However, choosing an appropriate chemotherapy agent is difficult because CRC is a heterogenous disease. It is believed that molecular stratification can help to improve treatment accuracy and this has been proven by the consensus molecular subtypes (CMS) classification. However, the CMS classification relies on expensive and complex gene-expression profiling, and more cumbersomely, is limited to early stage patients without prior chemotherapy, radiation and metastasis. This situation denies many CRC patients from the benefit of CMS classification. Circulating tumor DNA (ctDNA) is a minimally invasive way to monitor disease progression and treatment response in solid tumors but its clinical utility in CRC remains to be validated. We explore the potential of using patient’s fingerprint ctDNA (defined below) as a stratifying factor in CRC patients to assist clinical decision. Methods: WES is performed on tumor and matched blood samples from 149 CRC patients. Based on the WES result, 20-30 tumor specific genes are selected for each patient and form their ctDNA fingerprints. The patients are grouped according to their level of fingerprint ctDNA (high- vs. low-ctDNA). Results: The two groups of patients show significant difference in treatment responses and mutational profiles. The low-ctDNA group in general respond to treatment well and have good prognosis. The high-ctDNA group, in contrast, often experience relapse or recurrence. Interestingly, the low-ctDNA group is dominated by point and small indel mutations in the top mutated genes while the high-ctDNA group is dominated by gene copy variations (CNV). SMAD4 deficit and DCC amplification are well known CNV in CRC, but they only appear in the high-ctDNA group. Similarly, CNV of AGO2, ACTG1, MYC, and BRD3 are only associated with the high-ctDNA group but not the low-ctDNA group. Conclusions: Our result indicates a strong correlation of fingerprint ctDNA level to both tumor mutational profile and prognosis. This suggests fingerprint ctDNA level may be used as an effective stratifying factor in CRC. At the same time, possibly a common molecular cause is driving persistent ctDNA production in CRC patients, including a large portion of them who have received surgical and adjuvant chemotherapy. Further perspective study, however, is needed to test whether fingerprint ctDNA can be a predictive biomarker.

scholarly journals A prognostic index based on an eleven gene signature to predict systemic recurrences in colorectal cancer

2019 ◽  
Vol 51 (10) ◽  
pp. 1-12 ◽  
Author(s):  
Seon-Kyu Kim ◽  
Seon-Young Kim ◽  
Chan Wook Kim ◽  
Seon Ae Roh ◽  
Ye Jin Ha ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Risk ◽  
Adjuvant Chemotherapy ◽  
Biological Diversity ◽  
Cox Regression ◽  
Prognostic Index ◽  
Gene Signature ◽  
Rt Pcr ◽  
Transcriptomic Profiling ◽  
Cox Regression Analysis

Abstract Approximately half of colorectal cancer (CRC) patients experience disease recurrence and metastasis, and these individuals frequently fail to respond to treatment due to their clinical and biological diversity. Here, we aimed to identify a prognostic signature consisting of a small gene group for precisely predicting CRC heterogeneity. We performed transcriptomic profiling using RNA-seq data generated from the primary tissue samples of 130 CRC patients. A prognostic index (PI) based on recurrence-associated genes was developed and validated in two larger independent CRC patient cohorts (n = 795). The association between the PI and prognosis of CRC patients was evaluated using Kaplan–Meier plots, log-rank tests, a Cox regression analysis and a RT-PCR analysis. Transcriptomic profiling in 130 CRC patients identified two distinct subtypes associated with systemic recurrence. Pathway enrichment and RT-PCR analyses revealed an eleven gene signature incorporated into the PI system, which was a significant prognostic indicator of CRC. Multivariate and subset analyses showed that PI was an independent risk factor (HR = 1.812, 95% CI = 1.342–2.448, P < 0.001) with predictive value to identify low-risk stage II patients who responded the worst to adjuvant chemotherapy. Finally, a comparative analysis with previously reported Consensus Molecular Subgroup (CMS), high-risk patients classified by the PI revealed a distinct molecular property similar to CMS4, associated with a poor prognosis. This novel PI predictor based on an eleven gene signature likely represents a surrogate diagnostic tool for identifying high-risk CRC patients and for predicting the worst responding patients for adjuvant chemotherapy.

Sign in / Sign up

Export Citation Format

Share Document