Precision medicine for adjuvant chemotherapy of resected colorectal cancer
Ontology highlight
ABSTRACT:
SUBMITTER: Miyamoto Y
PROVIDER: S-EPMC7726679 | biostudies-literature | 2020 Nov
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundChemotherapy induced diarrhea (CID) is a common side effect in patients receiving chemotherapy for cancer. The aim of our study was to explore the association between gut microorganisms and CID from the CapeOX regimen in resected stage III colorectal cancer (CRC) patients.ResultsAfter screening and identification, 17 stool samples were collected from resected stage III CRC patients undergoing the CapeOX regimen. Bacterial 16S ribosomal RNA genes was sequenced, and a bioinformatics analysis was executed to screen for the distinctive gut microbiome and the functional metabolism associated with CID due to the CapeOX regimen. The gut microbial community richness and community diversity were lower in CID (p < 0.05 vs control group). Klebsiella pneumoniae was the most predominant species (31.22%) among the gut microbiome in CRC patients with CID. There were 75 microorganisms with statistically significant differences at the species level between the CRC patients with and without CID (LDA, linear discriminant analysis score > 2), and there were 23 pathways that the differential microorganisms might be involved in.ConclusionsThe gut microbial community structure and diversity have changed in CRC patients with CID. It may provide novel insights into the prevention and treatment of CID.
| S-EPMC6489188 | biostudies-literature
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.
| S-EPMC9381971 | biostudies-literature
Project description:The value of adjuvant chemotherapy in elderly patients has been the subject of many overviews, with opinions varying from "not effective", since randomized trials have not been performed, to "as effective as in young individuals", based upon many retrospective analyses of randomized trials that have included patients of all ages. In the absence of randomized trials performed specifically with elderly patients, retrospective analyses demonstrate that the influence on the time to tumour recurrence (TTR) may be the same as in young individuals, but that endpoints that include death for any reason, such as recurrence-free survival (RFS), disease-free survival (DFS), and overall survival (OS), are poorer in the elderly. This is particularly true if oxaliplatin has been part of the treatment. The need for adjuvant chemotherapy after colorectal cancer surgery in elderly patients is basically the same as that in younger patients. The reduction in recurrence risks may be similar, provided the chosen treatment is tolerated but survival gains are less. Adding oxaliplatin to a fluoropyrimidine is probably not beneficial in individuals above a biological age of approximately 70 years. If an oxaliplatin combination is administered to elderly patients, three months of therapy is in all probability the most realistic goal.
| S-EPMC7464071 | biostudies-literature
Project description:Background: The JBR.10 trial demonstrated significant survival benefit from adjuvant cisplatin/vinorelbine (ACT) in stage IB-II NSCLC (HR 0.69, p=0.04), but stage IB patients did not derive significant benefit (HR: 0.94, p= 0.79). We hypothesized that expression profiling could identify stage-independent subgroups of patients who might benefit from adjuvant chemotherapy. Methods: Gene expression profiling was conducted on mRNA isolated from frozen JBR.10 tumor samples (either from patients under observation [OBS], or treated with ACT). The minimum gene set that selected for the greatest separation of good and poor prognosis patient subgroups in OBS patients was identified and this gene signature was used to classify patients into high and low risk for death after surgery, and predict ACT effect. The prognostic gene signature was additionally tested on ACT patients and publicly available microarray datasets. Results: A 15-gene signature separated OBS patients into equal high and low risk subgroups with significantly different prognoses (HR 15.02, 95% CI 5.12-44.04, p=0.0001). The signature was prognostic in both stage IB and II. It was also predictive of improved survival following ACT treatment in high-risk patients (HR 0.33, 95% CI 0.17-0.63, p=0.0005), but not in low risk patients (HR 3.67, 95% CI 1.22-11.06, p=0.0133; interaction p=0.0001). The prognostic effect of the signature was validated in two independent gene expression datasets of 169 stage I-II adenocarcinoma and 106 squamous cell carcinoma patients. Conclusions: This microarray-based 15-gene prognostic expression signature is stage and histology independent and may select early stage NSCLC patients who are most likely to benefit from adjuvant chemotherapy with cisplatin/vinorelbine. Keywords: Expression profiling by microarray; prognosis prediction 90 samples
2010-09-09 | E-GEOD-14814 | biostudies-arrayexpress
Project description:Surgery is regarded as the primary treatment modality for early stage non-small cell lung cancer (NSCLC), but even after complete resection, a substantial percentage of these patients eventually develop local recurrence or distant metastases. Therefore more effective treatment strategies to reduce lung cancer mortality and recurrence rate are needed. Only recently has the use of adjuvant chemotherapy become standard in early stage NSCLC, at least for stage II and resected IIIA NSCLC. Controversies remain about the benefit for stage I patients. Five-year survival improvements of 5% to 10% have been reported with cisplatin-based adjuvant chemotherapy from multiple large randomized phase III clinical trials and meta-analyses. Questions remain as to which patients benefit and which regimens are best. In this paper, important clinical research in the field of adjuvant chemotherapy of NSCLC is reviewed.
| S-EPMC4367729 | biostudies-literature
Project description:BackgroundThe effectiveness of specific regimens of adjuvant therapy for gastric cancer has not been verified by large clinical trials. Recently, several large trials attempted to verify the effectiveness of adjuvant therapy. The Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer in Japan, a randomized controlled trial of adjuvant S-1 therapy for resected gastric cancer, demonstrated significant improvement in overall and relapse-free survival, compared to surgery alone. To evaluate value for money of S-1 therapy, cost-effective analysis was carried out.MethodsThe analysis was carried out from a payer's perspective. As an economic measure, cost per quality-adjusted life-year (QALY) gained was estimated. Overall survival was estimated by the Kaplan-Meier method, up to 5-year observation. Beyond this period, it was simulated by the modified Boag model. Utility score is derived from interviews with sampled patients using a time trade-off method. Costs were estimated from trial data during observation, while in the period beyond observation they were estimated using simulation results. To explore uncertainty of the results, qualitative and stochastic sensitivity analyses were done.ResultsAdjuvant S-1 therapy gained 1.24 QALYs per patient and increased costs by $3,722 per patient for over lifetime (3% discount rate for both effect and costs). The incremental cost-effectiveness ratio (95% confidence intervals) for over lifetime was estimated to be $3,016 ($1,441, $8,840) per QALY. The sensitivity analyses showed the robustness of these results.ConclusionAdjuvant S-1 therapy for curatively resected gastric cancer is likely cost-effective. This therapy can be accepted for wide use in Japan.
| S-EPMC3816158 | biostudies-literature
Project description:Globally, metastatic colorectal cancer is one of the leading causes for cancer-related death. Treatment limited to conventional chemotherapeutics extended life for only a few months. However, advances in surgical approaches and medical treatment regimens have greatly increased survival, even leading to long-term remission in selected patients. Advances in multiomics analysis of tumors have built a foundation for molecular-targeted therapies. Furthermore, immunotherapies are on the edge of revolutionizing oncological practice. This review summarizes recent advances in the growing toolbox of personalized treatment for patients with metastatic colorectal cancer. We provide an overview of current multimodal therapy and explain novel immunotherapy and targeted therapy approaches in detail. We emphasize clinically relevant therapies, such as inhibitors of MAPK signaling, and give recommendations for clinical practice. Finally, we describe the potential predictive impact of molecular subtypes and provide an outlook on novel concepts, such as functional precision medicine.
| S-EPMC8882813 | biostudies-literature
Project description:Colorectal cancer (CRC) is the third most commonly diagnosed cancer worldwide. Hereditary CRC syndromes account for approximately 5–10% of all CRC, with a lifetime risk of CRC that approaches 50–80% in the absence of endoscopic or surgical treatment. Hereditary CRC syndromes can be phenotypically divided into polyposis and non-polyposis syndrome, mainly according to the conditions of polyps. The typical representatives are familial adenomatous polyposis (FAP) and Lynch syndromes (LS), respectively. Over the past few decades, molecular genetics enhanced the discovery of cancer-predisposing genes and revolutionized the field of clinical oncology. Hereditary CRC syndromes have been a key part of this effort, with data showing that pathogenic variants are present in up to 10% of cases. Molecular phenotypes of tumors can not only help identify individuals with genetic susceptibility to CRC but also guide the precision prevention and treatment for the development of CRC. This review emphasizes the molecular basis and prevention strategies for hereditary CRC syndromes.
| S-EPMC9776295 | biostudies-literature
Project description:ImportanceThe benefit of adjuvant chemotherapy after resection of pancreatic cancer following neoadjuvant combination treatment with folinic acid, fluorouracil, irinotecan, and oxaliplatin (FOLFIRINOX) is unclear.ObjectiveTo assess the association of adjuvant chemotherapy with overall survival (OS) in patients after pancreatic cancer resection and neoadjuvant FOLFIRINOX treatment.Design, setting, and participantsThis international, multicenter, retrospective cohort study was conducted from January 1, 2012, to December 31, 2018. An existing cohort of patients undergoing resection of pancreatic cancer after FOLFIRINOX was updated and expanded for the purpose of this study. All consecutive patients who underwent pancreatic surgery after at least 2 cycles of neoadjuvant FOLFIRINOX chemotherapy for nonmetastatic pancreatic cancer were retrospectively identified from institutional databases. Patients with resectable pancreatic cancer, borderline resectable pancreatic cancer, and locally advanced pancreatic cancer were eligible for this study. Patients with in-hospital mortality or who died within 3 months after surgery were excluded.ExposuresThe association of adjuvant chemotherapy with OS was evaluated in different subgroups including interaction terms for clinicopathological parameters with adjuvant treatment in a multivariable Cox model. Overall survival was defined as the time starting from surgery plus 3 months (moment eligible for adjuvant therapy), unless mentioned otherwise.ResultsWe included 520 patients (median [interquartile range] age, 61 [53-66] years; 279 [53.7%] men) from 31 centers in 19 countries. The median number of neoadjuvant cycles of FOLFIRINOX was 6 (interquartile range, 5-8). Overall, 343 patients (66.0%) received adjuvant chemotherapy, of whom 68 (19.8%) received FOLFIRINOX, 201 (58.6%) received gemcitabine-based chemotherapy, 14 (4.1%) received capecitabine, 45 (13.1%) received a combination or other agents, and 15 (4.4%) received an unknown type of adjuvant chemotherapy. Median OS was 38 months (95% CI, 36-46 months) after diagnosis and 31 months (95% CI, 29-37 months) after surgery. No survival difference was found for patients who received adjuvant chemotherapy vs those who did not (median OS, 29 vs 29 months, univariable hazard ratio [HR], 0.99; 95% CI, 0.77-1.28; P = .93). In multivariable analysis, only the interaction term for lymph node stage with adjuvant therapy was statistically significant: In patients with pathology-proven node-positive disease, adjuvant chemotherapy was associated with improved survival (median OS, 26 vs 13 months; multivariable HR, 0.41 [95% CI, 0.22-0.75]; P = .004). In patients with node-negative disease, adjuvant chemotherapy was not associated with improved survival (median OS, 38 vs 54 months; multivariable HR, 0.85; 95% CI, 0.35-2.10; P = .73).Conclusions and relevanceThese results suggest that adjuvant chemotherapy after neoadjuvant FOLFIRINOX and resection of pancreatic cancer was associated with improved survival only in patients with pathology-proven node-positive disease. Future randomized studies should be conducted to confirm this finding.
| S-EPMC7489392 | biostudies-literature
Project description:Adjuvant chemotherapy for non-small-cell lung carcinoma (NSCLC) is a debated issue in clinical oncology. Although it is considered a standard for resected stage II-IIIA patients according to the available guidelines, many questions are still open. Among them, it should be acknowledged that the treatment for stage IB disease has shown so far a limited (if sizable) efficacy, the role of modern radiotherapies requires to be evaluated in large prospective randomized trials and the relative impact of age and comorbidities should be weighted to assess the reliability of the trials' evidences in the context of the everyday-practice. In addition, a conclusive evidence of the best partner for cisplatin is currently awaited as well as a deeper investigation of the fading effect of chemotherapy over time. The limited survival benefit since first studies were published and the lack of reliable prognostic and predictive factors beyond pathological stage, strongly call for the identification of bio-molecular markers and classifiers to identify which patients should be treated and which drugs should be used. Given the disappointing results of targeted therapy in this setting have obscured the initial promising perspectives, a biomarker-selection approach may represent the basis of future trials exploring adjuvant treatment for resected NSCLC.
| S-EPMC3284429 | biostudies-literature