Dataset Information

A Clinical-Genetic Score to Identify Surgically Resected Colorectal Cancer Patients Benefiting From an Adjuvant Fluoropyrimidine-Based Therapy.

ABSTRACT: There are clinical challenges related to adjuvant treatment in colorectal cancer (CRC) and novel molecular markers are needed for better risk stratification of patients. Our aim was to integrate our previously reported clinical-genetic prognostic score with new immunogenetic markers of 5-year disease-free survival (DFS) to evaluate the recurrence risk stratification before fluoropyrimidine (FL)-based adjuvant therapy. The study population included a total of 270 stage II-III CRC patients treated with adjuvant FL with (FL + OXA, n = 119) or without oxaliplatin (FL, n = 151). Patients were genotyped for a panel of 192 tagging polymorphisms in 34 immune-related genes. The IFNG-rs1861494 polymorphism was associated with worse DFS in the FL + OXA (HR = 2.14, 95%CI 1.13-4.08; P = 0.020, q-value = 0.249) and FL (HR = 1.97, 95%CI 1.00-3.86; P = 0.049) cohorts, according to a dominant model. The integration of IFNG-rs1861494 in our previous clinical genetic multiparametric score of DFS improved the patients' risk stratification (Log-rank P = 0.0026 in the pooled population). These findings could improve the discrimination of patients who would benefit from adjuvant treatment. In addition, the results may help better elucidate the interplay between the immune system and chemotherapeutics and help determine the efficacy of anti-tumor strategies.

SUBMITTER: De Mattia E

PROVIDER: S-EPMC6180157 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A Clinical-Genetic Score to Identify Surgically Resected Colorectal Cancer Patients Benefiting From an Adjuvant Fluoropyrimidine-Based Therapy.

De Mattia Elena E Dreussi Eva E Montico Marcella M Gagno Sara S Zanusso Chiara C Quartuccio Luca L De Vita Salvatore S Guardascione Michela M Buonadonna Angela A D'Andrea Mario M Pella Nicoletta N Favaretto Adolfo A Mini Enrico E Nobili Stefania S Romanato Loredana L Cecchin Erika E Toffoli Giuseppe G

Frontiers in pharmacology 20181004

There are clinical challenges related to adjuvant treatment in colorectal cancer (CRC) and novel molecular markers are needed for better risk stratification of patients. Our aim was to integrate our previously reported clinical-genetic prognostic score with new immunogenetic markers of 5-year disease-free survival (DFS) to evaluate the recurrence risk stratification before fluoropyrimidine (FL)-based adjuvant therapy. The study population included a total of 270 stage II-III CRC patients treated ...[more]

PMID: 30337874

Similar Datasets

Project description:BackgroundPatients with colorectal cancer (CRC) are more likely to develop cardiovascular disease (CVD) than those without cancer. Little is known regarding their CV risk after operative chemotherapy. We aimed to compare the risk of CV disease among different fluoropyrimidine derivatives.MethodsWe assembled a nationwide cohort of patients with newly diagnosed CRC between 2004 and 2015 who received fluoropyrimidine-based adjuvant chemotherapy for resected CRC by linking the Taiwan Cancer Registry (TCR), National Health Insurance Research Database (NHIRD), and Taiwan Death Registry (TDR). All eligible patients were followed from CRC diagnosis (index date) until a CV event, death, loss to follow-up, or December 31st 2018, whichever came first. CV outcomes included acute myocardial infarction (AMI), life-threatening arrhythmia (LTA), congestive heart failure (CHF), and ischemic stroke (IS). We used stabilized inverse probability of treatment weighting using propensity score (SIPTW) to balance all covariates among the three chemotherapy groups: tegafur-uracil (UFT), non-UFT, and mixed. In addition, survival analysis was conducted to examine the association between study outcomes and chemotherapy groups.ResultsFrom 2004 to 2015, 10,615 (32.8%) patients received UFT alone, 14,511 (44.8%) patients received non-UFT, and 7,224 (22.3%) patients received mixed chemotherapy. After SIPTW, the UFT group had significantly lower all-cause mortality and cancer-related death rates than the other two chemotherapy groups. However, the UFT group had significantly higher rates of cancer death, ischemic stroke, and heart failure than those of the other two chemotherapy groups. The UFT group also had a significantly higher AMI rate than the mixed group. There was no significant difference in LTA among the three groups. Similar findings were observed in the subgroup analysis (stage II and age <70 years, stage II and age ≥70 years, stage III and age <70 years, stage III and age ≥70 years) as the overall population was observed.ConclusionHigher heart failure and ischemic stroke rates were found in the UFT group than in the other two chemotherapy groups, especially those with stage III CRC and ≥70 years of age. Careful monitoring of this subset of patients when prescribing UFT is warranted.

Project description:ObjectivePlatelets have been implicated in cancer metastasis and prognosis. No population-based study has been reported as to whether preoperative platelet count directly predicts metastatic recurrence of colorectal cancer (CRC) patients.DesignUsing a well-characterized cohort of 1,513 surgically resected CRC patients, we assessed the predictive roles of preoperative platelet count in overall survival, overall recurrence, as well as locoregional and distant metastatic recurrences.ResultsPatients with clinically high platelet count (≥400 × 10(9)/L) measured within 1 month before surgery had a significantly unfavorable survival (hazard ratio [HR] = 1.66, 95 % confidence interval [CI] 1.34-2.05, P = 2.6 × 10(-6), P(log rank) = 1.1 × 10(-11)) and recurrence (HR = 1.90, 1.24-2.93, P = 0.003, P(log rank) = 0.003). The association of platelet count with recurrence was evident only in patients with metastatic (HR = 2.81, 1.67-4.74, P = 1.1 × 10(-4), P(log rank) = 2.6 × 10(-6)) but not locoregional recurrence (HR = 0.59, 95 % CI 0.21-1.68, P = 0.325, P(log rank) = 0.152). The findings were internally validated through bootstrap resampling (P < 0.01 at 98.6 % of resampling). Consistently, platelet count was significantly higher in deceased than living patients (P < 0.0001) and in patients with metastatic recurrence than locoregional (P = 0.004) or nonrecurrent patients (P < 0.0001). Time-dependent modeling indicated that the increased risks for death and metastasis associated with elevated preoperative platelet counts persisted up to 5 years after surgery.ConclusionOur data demonstrated that clinically high level of preoperative platelets was an independent predictor of CRC survival and metastasis. As an important component of the routinely tested complete blood count panel, platelet count may be a cost-effective and noninvasive marker for CRC prognosis and a potential intervention target to prevent metastatic recurrence.

Project description:Background6 months of oxaliplatin-containing chemotherapy is usually given as adjuvant treatment for stage 3 colorectal cancer. We investigated whether 3 months of oxaliplatin-containing chemotherapy would be non-inferior to the usual 6 months of treatment.MethodsThe SCOT study was an international, randomised, phase 3, non-inferiority trial done at 244 centres. Patients aged 18 years or older with high-risk stage II and stage III colorectal cancer underwent central randomisation with minimisation for centre, choice of regimen, sex, disease site, N stage, T stage, and the starting dose of capecitabine. Patients were assigned (1:1) to receive 3 months or 6 months of adjuvant oxaliplatin-containing chemotherapy. The chemotherapy regimens could consist of CAPOX (capecitabine and oxaliplatin) or FOLFOX (bolus and infused fluorouracil with oxaliplatin). The regimen was selected before randomisation in accordance with choices of the patient and treating physician. The primary study endpoint was disease-free survival and the non-inferiority margin was a hazard ratio of 1·13. The primary analysis was done in the intention-to-treat population and safety was assessed in patients who started study treatment. This trial is registered with ISRCTN, number ISRCTN59757862, and follow-up is continuing.Findings6088 patients underwent randomisation between March 27, 2008, and Nov 29, 2013. The intended treatment was FOLFOX in 1981 patients and CAPOX in 4107 patients. 3044 patients were assigned to 3 month group and 3044 were assigned to 6 month group. Nine patients in the 3 month group and 14 patients in the 6 month group did not consent for their data to be used, leaving 3035 patients in the 3 month group and 3030 patients in the 6 month group for the intention-to-treat analyses. At the cutoff date for analysis, there had been 1482 disease-free survival events, with 740 in the 3 month group and 742 in the 6 month group. 3 year disease-free survival was 76·7% (95% CI 75·1-78·2) for the 3 month group and 77·1% (75·6-78·6) for the 6 month group, giving a hazard ratio of 1·006 (0·909-1·114, test for non-inferiority p=0·012), significantly below the non-inferiority margin. Peripheral neuropathy of grade 2 or worse was more common in the 6 month group (237 [58%] of 409 patients for the subset with safety data) than in the 3 month group (103 [25%] of 420) and was long-lasting and associated with worse quality of life. 1098 serious adverse events were reported (492 reports in the 3 month group and 606 reports in the 6 month group) and 32 treatment-related deaths occurred (16 in each group).InterpretationIn the whole study population, 3 months of oxaliplatin-containing adjuvant chemotherapy was non-inferior to 6 months of the same therapy for patients with high-risk stage II and stage III colorectal cancer and was associated with reduced toxicity and improved quality of life. Despite the fact the study was underpowered, these data suggest that a shorter duration leads to similar survival outcomes with better quality of life and thus might represent a new standard of care.FundingMedical Research Council, Swedish Cancer Society, NETSCC, and Cancer Research UK.

Dataset Information

A Clinical-Genetic Score to Identify Surgically Resected Colorectal Cancer Patients Benefiting From an Adjuvant Fluoropyrimidine-Based Therapy.

Publications

A Clinical-Genetic Score to Identify Surgically Resected Colorectal Cancer Patients Benefiting From an Adjuvant Fluoropyrimidine-Based Therapy.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets