A Controlled Prospective Trial of Adjuvant Razoxane in Resectable Colorectal Cancer

1981 ◽  
pp. 48-58 ◽  
Author(s):  
J. M. Gilbert ◽  
P. C. Cassell ◽  
H. Ellis ◽  
C. Wastell ◽  
K. Hellmann ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Prospective Trial

scholarly journals A Serum Metabolomics Classifier Derived from Elderly Patients with Metastatic Colorectal Cancer Predicts Relapse in the Adjuvant Setting

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2762
Author(s):  
Samantha Di Donato ◽  
Alessia Vignoli ◽  
Chiara Biagioni ◽  
Luca Malorni ◽  
Elena Mori ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Risk Stratification ◽  
Elderly Patients ◽  
Metastatic Colorectal Cancer ◽  
Early Stage ◽  
Prospective Trial ◽  
Proton Nuclear Magnetic Resonance ◽  
P Value ◽  
Resonance Spectroscopy ◽  
Metabolomic Fingerprinting

Adjuvant treatment for patients with early stage colorectal cancer (eCRC) is currently based on suboptimal risk stratification, especially for elderly patients. Metabolomics may improve the identification of patients with residual micrometastases after surgery. In this retrospective study, we hypothesized that metabolomic fingerprinting could improve risk stratification in patients with eCRC. Serum samples obtained after surgery from 94 elderly patients with eCRC (65 relapse free and 29 relapsed, after 5-years median follow up), and from 75 elderly patients with metastatic colorectal cancer (mCRC) obtained before a new line of chemotherapy, were retrospectively analyzed via proton nuclear magnetic resonance spectroscopy. The prognostic role of metabolomics in patients with eCRC was assessed using Kaplan–Meier curves. PCA-CA-kNN could discriminate the metabolomic fingerprint of patients with relapse-free eCRC and mCRC (70.0% accuracy using NOESY spectra). This model was used to classify the samples of patients with relapsed eCRC: 69% of eCRC patients with relapse were predicted as metastatic. The metabolomic classification was strongly associated with prognosis (p-value 0.0005, HR 3.64), independently of tumor stage. In conclusion, metabolomics could be an innovative tool to refine risk stratification in elderly patients with eCRC. Based on these results, a prospective trial aimed at improving risk stratification by metabolomic fingerprinting (LIBIMET) is ongoing.

scholarly journals Colorectal cancer screening using a stool DNA-based SDC2 methylation test: a multicenter, prospective trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Chang Woo Kim ◽  
Hyunjin Kim ◽  
Hyoung Rae Kim ◽  
Bong-Hyeon Kye ◽  
Hyung Jin Kim ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Colon Cancer ◽  
Early Detection ◽  
Prospective Trial ◽  
Screening Colonoscopy ◽  
Quantitative Detection ◽  
Screening Programs ◽  
Crc Screening ◽  
Stool Dna ◽  
Dna 2

Abstract Background Prevention and early detection of colorectal cancer (CRC) is a global priority, with many countries conducting population-based CRC screening programs. Although colonoscopy is the most accurate diagnostic method for early CRC detection, adherence remains low because of its invasiveness and the need for extensive bowel preparation. Non-invasive fecal occult blood tests or fecal immunochemical tests are available; however, their sensitivity is relatively low. Syndecan-2 (SDC2) is a stool-based DNA methylation marker used for early detection of CRC. Using the EarlyTect™-Colon Cancer test, the sensitivity and specificity of SDC2 methylation in stool DNA for detecting CRC were previously demonstrated to be greater than 90%. Therefore, a larger trial to validate its use for CRC screening in asymptomatic populations is now required. Methods All participants will collect their stool (at least 20 g) before undergoing screening colonoscopy. The samples will be sent to a central laboratory for analysis. Stool DNA will be isolated using a GT Stool DNA Extraction kit, according to the manufacturer’s protocol. Before performing the methylation test, stool DNA (2 µg per reaction) will be treated with bisulfite, according to manufacturer’s instructions. SDC2 and COL2A1 control reactions will be performed in a single tube. The SDC2 methylation test will be performed using an AB 7500 Fast Real-time PCR system. CT values will be calculated using the 7500 software accompanying the instrument. Results from the EarlyTect™-Colon Cancer test will be compared against those obtained from colonoscopy and any corresponding diagnostic histopathology from clinically significant biopsied or subsequently excised lesions. Based on these results, participants will be divided into three groups: CRC, polyp, and negative. The following clinical data will be recorded for the participants: sex, age, colonoscopy results, and clinical stage (for CRC cases). Discussion This trial investigates the clinical performance of a device that allows quantitative detection of a single DNA marker, SDC2 methylation, in human stool DNA in asymptomatic populations. The results of this trial are expected to be beneficial for CRC screening and may help make colonoscopy a selective procedure used only in populations with a high risk of CRC. Trial registration: This trial (NCT04304131) was registered at ClinicalTrials.gov on March 11, 2020 and is available at https://clinicaltrials.gov/ct2/show/NCT04304131?cond=NCT04304131&draw=2&rank=1.

Intratumoral mRNA levels predict clinical outcome in patients with metastatic colorectal cancer treated in a prospective clinical trial with 5-FU and oxaliplatin

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10010-10010
Author(s):  
D. Yang ◽  
D. Vallböhmer ◽  
W. Zhang ◽  
S. Iqbal ◽  
A. El-Khoueiry ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Dna Repair ◽  
Clinical Outcome ◽  
Prospective Trial ◽  
Progression Free Survival ◽  
Rank Test ◽  
Mrna Levels ◽  
Second Line ◽  
Tissue Samples ◽  
Cox 2

10010 Background: 5-flurouracil (5-FU) and Oxaliplatin-based therapy is one of the most frequently used combinations in the treatment of advanced colorectal cancer (CRC). There are no validated and established predictive factors for clinical outcome following 5-FU/Oxaliplatin treatment. We had shown an association between intratumoral mRNA levels of TS and ERCC1 involved in 5-FU metabolism and DNA repair, respectively, and survival to 5-FU/Oxaliplatin chemotherapy in advanced CRC in a retrospective study. Now we investigated whether intratumoral mRNA levels of these two genes and others involved in 5-FU metabolism (DPD, TP, dUTPase), DNA repair (ERCC2, XRCC1), angiogenesis (COX-2, EGFR, IL-8, PLA2), and drug detoxification (GSTP-1) predict the clinical outcome of patients with CRC in a prospectively designed biomarker study. Methods: 85 patients with metastatic CRC treated with second-line 5-FU/Oxaliplatin from the prospective trial were included. mRNA levels of 12 genes were assessed from paraffin- embedded tissue samples using laser capture microdissection and quantitative Real-time PCR. Overall survival (OS) was the primary endpoint. Progression-free survival (PFS), response, and toxicity were the secondary endpoints. Results: There were 40 women and 45 men (median age 60 years; range 29–87), median survival of 9.7 ms, median PFS of 4.2 ms, CR in 1 (1%) patient, PR in 15 (18%), SD in 36 (43%) and PD in 32 (38%) patients. High intratumoral mRNA levels of PLA2, TP, GSPTP-1 and low mRNA levels of COX-2 were each significantly associated with shorter OS (P≤0.05, log-rank test). There was a trend in the association between high mRNA levels of PLA2 and shorter PFS (P=0.08). In addition, high mRNA levels of XRCC1 and IL-8 were each significantly associated with high risk of cumulative grade 3+ toxicity (P≤0.05). No significant association was found between mRNA levels and response to 5-FU/Oxaliplatin. Conclusions: This study suggests that mRNA levels of PLA2, TP, GSTP-1, COX-2, XRCC1, and IL-8 may be useful to predict the outcome of patients with metastatic CRC with second-line 5-FU/Oxaliplatin chemotherapy. These findings should be validated with future basic sciences studies and prospective clinical trials. [Table: see text]

MMP-7 serum levels as predictor or prognostic of cetuximab benefit in the treatment of advanced colorectal cancer: Results from a HCB-05 prospective trial.

2010 ◽  
Vol 28 (15_suppl) ◽  
pp. 10639-10639
Author(s):  
G. Carrera ◽  
X. Garcia-Albeniz ◽  
V. Alonso-Espinaco ◽  
C. Pericay ◽  
V. Alonso ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Advanced Colorectal Cancer ◽  
Prospective Trial ◽  
Serum Levels

scholarly journals ONCOGRAM: study protocol for the evaluation of therapeutic response and survival of metastatic colorectal cancer patients treated according to the guidelines of a chemosensitivity assay, the Oncogramme®

Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Muriel Mathonnet ◽  
Mathieu Vanderstraete ◽  
Christophe Bounaix Morand du Puch ◽  
Stéphanie Giraud ◽  
Christophe Lautrette ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Decision Support ◽  
Metastatic Colorectal Cancer ◽  
Survival Rates ◽  
Prospective Trial ◽  
Progression Free Survival ◽  
Decision Support Tool ◽  
Chemosensitivity Assay ◽  
Free Survival ◽  
Support Tool

Abstract Background Colorectal cancer is a major public concern, being the second deadliest cancer in the world. Whereas survival is high for localized forms, metastatic colorectal cancer has showed poor prognosis, with a 5-year survival barely surpassing 11%. Conventional chemotherapies against this disease proved their efficiency and remain essential in first-line treatment. However, the large number of authorized protocols complexifies treatment decision. In common practice, such decision is made on an empirical basis, by assessing benefits and risks for the patient. In other words, there is currently no efficient means of predicting the efficacy of any chemotherapy protocol for metastatic colorectal cancer. Methods/design The use of a chemosensitivity assay, the Oncogramme®, should help clinicians administer the best chemotherapy regimen to their patients. We hypothesize it would ultimately improve their survival. In this multicentred, prospective trial (ONCOGRAM), eligible patients with metastatic colorectal cancer are randomized to determine whether they will receive an Oncogramme®. For clinicians whose patients benefited from the assay (arm A), results are used as a decision support tool. Patients not undergoing the Oncogramme® procedure are treated according to current practice, without the assistance of the assay (arm B). Primary outcome is 1-year progression-free survival. Secondary outcomes include response rates, as well as 6-month and 1-year survival rates. Discussion This study aims at investigating the clinical utility of the Oncogramme® as a decision support tool for the treatment of patients with metastatic colorectal cancer. If the Oncogramme® positively influenced patient overall survival and/or progression-free survival, it would be of great value for clinicians to implement this assay within the current landscape of personalized medicine tools, which include genomics and biomarker assays. Trial registration ClinicalTrials.gov identifier NCT03133273. Registered on April 28, 2017.

Multicenter trial for assessing cytokine promoter gene polymorphism as a predictive parameter of PSK responder for curatively resected stage II or III colorectal cancer.

2015 ◽  
Vol 33 (3_suppl) ◽  
pp. 619-619
Author(s):  
Shigefumi Yoshino ◽  
Furuya Takumi ◽  
Koichiro Sakata ◽  
Ryoichi Shimizu ◽  
Naoko Okayama ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Curative Resection ◽  
Cytokine Production ◽  
Prospective Trial ◽  
Disease Recurrence ◽  
Multicenter Trial ◽  
Stage Ii ◽  
Stage Iii ◽  
Tnf Α ◽  
Promoter Gene

619 Background: Polysaccharide-K (PSK), a protein-bound polysaccharide extracted from the mycelia of Coriolus versicolor, is an immunomodulator widely used in colorectal cancer in Japan. PSK has immunological actions including enhancement or inhibition of cytokine production. It has been reported that levels of cytokine production are influenced by polymorphisms in the promoters of cytokine genes. We hypothesized that cytokine promoter gene polymorphisms may be responsible for genetic susceptibilities to immunological effect of PSK. Methods: This is a multicenter prospective trial. One hundred and ten patients with stage II or III colorectal cancer were enrolled. All patients received adjuvant immnochemotherapy after curative resection using UFT (stage II) or UFT/LV (stage III) combined with PSK (3.0 g/day, p.o.) for 1 year. Post-operative survey of recurrence was followed with CT scan at 6-month intervals during the first 2 years after surgery and at 1-year intervals thereafter until 5 year after surgery. DNA was extracted from peripheral blood cells in all patients. The following polymorphisms of the patients were genotyped: TNF-α-1031T/C, IL-1ß-511C/T, IL-6-634C/G, IL-10-819T/C. Results: Twenty (6 in stage II, 14 in stage III) out of 110 patients showed recurrence after more than 5 years survey. Fifteen out of 74 patients with TNF-α-1031 TT genotype and 5 out of 36 with TNF-α-1031 CC or CT showed disease recurrence. Five out of 39 patients with IL-1ß-511 CC and 15 out of 71 with IL-1ß-511 CT or TT showed disease recurrence. Eleven out of 61 patients with IL-6-634 CC and 9 out of 49 with IL-6-634 CG or GG showed disease recurrence. No association between genotype frequency and disease recurrence was observed for TNF-α, IL-1ß, IL-6. Fifteen out of 61 patients with IL-10-819 CC or CT genotype showed disease recurrence, whereas only 5 out of 49 with IL-10-819 TT showed tumor recurrence (p=0.052). Especially, significant association with disease recurrence was found in stage III patients (12/30 vs 2/17, p=0.042). Conclusions: It is suggested that colorectal cancer patients with IL-10-819 TT genotype could be PSK responder after curative resection.

scholarly journals Genomic and transcriptomic determinants of therapy resistance and immune landscape evolution during anti-EGFR treatment in colorectal cancer

2018 ◽  
Author(s):  
Andrew Woolston ◽  
Khurum Khan ◽  
Georgia Spain ◽  
Louise J Barber ◽  
Beatrice Griffiths ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Prospective Trial ◽  
Genetic Resistance ◽  
Growth Factor Receptor ◽  
Therapy Resistance ◽  
Wild Type ◽  
Epidermal Growth ◽  
Novel Associations

AbstractAnti-epidermal growth factor receptor (EGFR) antibodies (anti-EGFR-Ab) are effective in a subgroup of patients with metastatic colorectal cancer (CRC). We applied genomic and transcriptomic analyses to biopsies from 35 RAS wild-type CRCs treated with the anti-EGFR-Ab cetuximab in a prospective trial to interrogate the molecular resistance landscape. This validated transcriptomic CRC-subtypes as predictors of cetuximab benefit; identified novel associations of NF1-inactivation and non-canonical RAS/RAF-aberrations with primary progression; and of FGF10- and non-canonical BRAF-aberrations with AR. No genetic resistance drivers were detected in 64% of AR biopsies. The majority of these had switched from the cetuximab-sensitive CMS2-subtype pretreatment to the fibroblast- and growth factor-rich CMS4-subtype at progression. Fibroblast supernatant conferred cetuximab resistance in vitro, together supporting subtype-switching as a novel mechanism of AR. Cytotoxic immune infiltrates and immune-checkpoint expression increased following cetuximab responses, potentially providing opportunities to treat CRCs with molecularly heterogeneous AR with immunotherapy.

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