Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Organ Preservation Strategies After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer.

ABSTRACT: Standard use of neoadjuvant chemoradiotherapy, total mesorectal excision, and postoperative adjuvant chemotherapy in locally advanced rectal cancer has tremendously improved oncologic outcomes over the past several decades. However, these improvements come with costs of significant morbidity and poor quality of life. Along with developments in imaging techniques, clinical experience and evidence have identified a certain subgroup of patients that have exceptionally good clinical outcomes while preserving quality of life. Driven by patient demand and interest in preserving quality of life, numerous organ preservation treatment strategies for managing rectal cancer are rapidly evolving. Herein, the flow of research in organ preservation strategies and counter arguments are discussed.

SUBMITTER: Yoo RN

PROVIDER: S-EPMC6529751 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Organ Preservation Strategies After Neoadjuvant Chemoradiotherapy for Locally Advanced Rectal Cancer.

Yoo Ri Na RN Kim Hyung Jin HJ

Annals of coloproctology 20190430 2

Standard use of neoadjuvant chemoradiotherapy, total mesorectal excision, and postoperative adjuvant chemotherapy in locally advanced rectal cancer has tremendously improved oncologic outcomes over the past several decades. However, these improvements come with costs of significant morbidity and poor quality of life. Along with developments in imaging techniques, clinical experience and evidence have identified a certain subgroup of patients that have exceptionally good clinical outcomes while p ...[more]

PMID: 31113170

Similar Datasets

Neoadjuvant chemoradiotherapy combined with immunotherapy for locally advanced rectal cancer: A new era for anal preservation.

Project description:For locally advanced (T3-4/N+M0) rectal cancer (LARC), neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) is the standard treatment. It was demonstrated to decrease the local recurrence rate and increase the tumor response grade. However, the distant metastasis remains an unresolved issue. And the demand for anus preservation and better quality of life increases in recent years. Radiotherapy and immunotherapy can be supplement to each other and the combination of the two treatments has a good theoretical basis. Recently, multiple clinical trials are ongoing in terms of the combination of nCRT and immunotherapy in LARC. It was reported that these trials achieved promising short-term efficacy in both MSI-H and MSS rectal cancers, which could further improve the rate of clinical complete response (cCR) and pathological complete response (pCR), so that increase the possibility of 'Watch and Wait (W&W)' approach. However, the cCR and pCR is not always consistent, which occurs more frequent when nCRT is combined with immunotherapy. Thus, the efficacy evaluation after neoadjuvant therapy is an important issue for patient selection of W&W approach. Evaluating the cCR accurately needs the combination of multiple traditional examinations, new detective methods, such as PET-CT, ctDNA-MRD and various omics studies. And finding accurate biomarkers can help guide the risk stratification and treatment decisions. And large-scale clinical trials need to be performed in the future to demonstrate the surprising efficacy and to explore the long-term prognosis.

| S-EPMC9772444 | biostudies-literature

Meta-analysis of neoadjuvant chemotherapy versus neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

Project description:Background and purposeWith the advent of more intensive chemotherapy regimens, neoadjuvant chemoradiotherapy (NACRT) for patients with locally advanced rectal cancer (LARC) has always been questioned due to its inevitable radiation toxicity. Hence, we conducted a meta-analysis to compare the clinical efficacy of neoadjuvant chemotherapy (NAC) and NACRT.Materials and methodsEligible studies were searched using PubMed, MEDLINE, Embase, the Cochrane Library, and Web of Science up to 31 July 2020, comparing the clinical efficacy of NAC versus NACRT for LARC. Short- and long-term outcomes were determined using the odds ratio (OR) with 95% confidence interval (CI).ResultsSix studies with 12,812 patients were eligible for this meta-analysis, including 677 patients in the NAC group and 12,135 patients in the NACRT group. There were no significant differences between the two groups in terms of pathological complete response rate (OR=0.62, 95%CI=0.27~1.41), N down-staging rate (OR=1.20, 95%CI=0.25~5.79), R0 resection rate (OR=1.24, 95%CI=0.78~1.98), and local relapse rate (OR=1.12, 95%CI=0.58~2.14). The pooled OR for the total response rate and T down-staging were in favor of NACRT (OR=0.41, 95%CI=0.22~0.76 versus OR=0.67 95%CI=0.52~0.87). However, the pooled OR for the sphincter preservation rate favored NAC compared with NACRT (OR=1.87, 95%CI=1.24~2.81). Moreover, NAC was found to be superior to NACRT in terms of distant metastasis (14.3% vs. 20.4%), but the difference was not significant (OR=0.84, 95%CI=0.31~2.27).ConclusionWe concluded that NAC was superior to NACRT in terms of the sphincter preservation rate, and non-inferior to NACRT in terms of pCR, N down-staging, R0 resection, local relapse, and distant metastasis. However, the conclusion warrants further validation.

| S-EPMC8101236 | biostudies-literature

Locally advanced rectal cancer transcriptomic-based secretome analysis according to neoadjuvant chemoradiotherapy response

Project description:Most patients with locally advanced rectal cancer (LARC) present incomplete pathological response (pIR) to neoadjuvant chemoradiotherapy (nCRT). Despite the efforts to predict treatment response using tumor-molecular features, as differentially expressed genes, no molecule has proved to be a strong biomarker. The tumor secretome analysis is a promising strategy for biomarkers identification, which can be assessed using transcriptomic data. Here, we performed transcriptomic-based secretome analysis to select potentially secreted proteins using an in silico approach. The tumor expression profile of 28 LARC biopsies carefully selected and collected before nCRT was compared with normal rectal tissues (NT). The expression profile showed no significant differences between cases with complete (pCR) and incomplete response to nCRT. Genes with increased expression (pCR = 106 and pIR = 357) were used for secretome analysis based on public databases (Vesiclepedia, Human Cancer Secretome Database and Plasma and Proteome Database). Seventeen potentially secreted candidates (pCR=1, pIR=13 and 3 in both groups) were further investigated in two independent datasets (TCGA and GSE68204) confirming their over-expression in LARC. The potential secreted biomarkers were also confirmed as associated with the nCRT response (GSE68204). These putative proteins are candidates to be assessed in liquid biopsies aiming a personalized treatment in LARC patients.

2019-07-01 | GSE123390 | GEO

Outcomes of neoadjuvant chemoradiotherapy in Japanese locally advanced rectal carcinoma patients.

Project description:We investigated the efficacy and prognosis of neoadjuvant chemoradiotherapy (NACRT) for Japanese locally advanced rectal carcinoma patients.Fifty-seven patients diagnosed with cT3-4 or any cT/cN+ disease using enhanced computed tomography or magnetic resonance imaging from 2002 to 2014 were enrolled. The male/female ratio was 42/15, and the median age was 67 years. Ra/Rb/Rb-P/P was expressed by 6/35/14/2 patients. Histological tumor types were tub1/tub2/por/muc in 22/30/4/1 patients. For NACRT, radiotherapy doses were 40-50.4 Gy chemotherapy consisted of 5'-DFUR, capecitabine, or S1.All 57 patients received curative surgical treatment. The anal preservation rate was 65.0%. The ypStage of 0/I/II/IIIa/IIIb was 7/10/25/11/4 cases. The histological antitumor effect (HATE) was ?grade (G) 2 and G3 in 31 (54.4%) and 7 (12.3%) cases, respectively. Postoperative complications occurred in 17 patients and exceeded GIII (Clavien-Dindo classification) in four patients. Recurrence was observed in 19 patients; the primary local recurrence rate was 5.3%. The 3-year relapse-free survival (RFS) and overall survival (OS) rates were 64.8 and 95.5%, respectively; the 5-year RFS and OS rates were 60.2 and 61.0%, respectively. In multivariate analysis, ypN+ was a high-risk factor for distant organ recurrence. As predictive factors regarding the efficacy of NACRT, a neutrophil concentration <70% and a neutrophil/lymphocyte ratio <3.0 in peripheral blood prior to treatment indicated that NACRT would be significantly more effective.NACRT was effective in reducing local recurrence but did not suppress distant organ recurrence in Japanese locally advanced rectal carcinoma patients. A further investigation of an extension of the NACRT regimen is required.

| S-EPMC4851776 | biostudies-other

Selecting patients with locally advanced rectal cancer for neoadjuvant treatment strategies.

Project description:Rectal cancer remains a significant problem worldwide. Outcomes vary significantly according to the stage of disease and prognostic factors, including the distance of the tumor from the circumferential resection margin. Accurate staging, including high-resolution magnetic resonance imaging, allows stratification of patients into low-, moderate-, and high-risk disease; this information can be used to inform multidisciplinary team decisions regarding the role of neoadjuvant therapy. Both neoadjuvant short-course radiotherapy and long-course chemoradiation reduce the risk of local recurrence compared with surgery alone, but they have little impact on survival. Although there remains a need to reduce overtreatment of those patients at moderate risk, evaluation of intensified regimens for those with high-risk disease is still required to reduce distant failure rates and improve survival in these patients with an otherwise poor prognosis.

| S-EPMC3720638 | biostudies-literature

Pretreatment TACC3 expression in locally advanced rectal cancer decreases the response to neoadjuvant chemoradiotherapy.

Project description:Chemoradiotherapy combined with surgical resection is the standard treatment for locally advanced rectal cancer, but not all the patients respond to neoadjuvant treatment. Transforming acidic coiled-coil protein-3 (TACC3) is frequently aberrantly expressed in rectal cancer tissue. In this study, we investigated whether TACC3 could serve as a biomarker predictive of the efficacy of chemoradiotherapy. In all, 152 rectal cancer patients with tumor tissue collected at biopsy and set aside before treatment were enrolled in this study. All patients received chemoradiotherapy and surgical resection. Immunohistochemically detected tumoral TACC3 expression significantly decreased sensitivity to chemoradiotherapy [risk ratio (RR) = 2.236, 95% confidence interval (CI): 1.447-3.456; P = 0.001] and thus the pathological complete response rate (P = 0.001). TACC3 knockdown using specific siRNA enhanced radiotherapy-induced decreases in proliferation and colony formation by HCT116 and SW480 cells and increased the incidence of radiotherapy-induced apoptosis. Cox multivariate analysis showed that TACC3 was a significant prognostic factor for overall survival (P = 0.017) and disease-free survival (P = 0.020). These findings suggest TACC3 expression may be predictive of chemoradiotherapy sensitivity and prognosis in locally advanced rectal cancer.

| S-EPMC6224241 | biostudies-other

Extended Intervals after Neoadjuvant Therapy in Locally Advanced Rectal Cancer: The Key to Improved Tumor Response and Potential Organ Preservation.

Project description:Many rectal cancer patients experience tumor downstaging and some are found to achieve a pathologic complete response (pCR) after neoadjuvant chemoradiotherapy (nCRT). Previous data suggest that there is an association between the time interval from nCRT completion to surgery and tumor response rates, including pCR. However, these studies have been primarily from single institutions with small sample sizes. The aim of this study was to examine the relationship between a longer interval after nCRT and pCR in a nationally representative cohort of rectal cancer patients.Clinical stage II to III rectal cancer patients undergoing nCRT with a documented surgical resection were selected from the 2006 to 2011 National Cancer Data Base. Multivariable logistic regression analysis was used to assess the association between the nCRT-surgery interval time (<6 weeks, 6 to 8 weeks, >8 weeks) and the odds of pCR. The relationship between nCRT-surgery interval, surgical morbidity, and tumor downstaging was also examined.Overall, 17,255 patients met the inclusion criteria. An nCRT-surgery interval time >8 weeks was associated with higher odds of pCR (odds ratio [OR] 1.12, 95% CI 1.01 to 1.25) and tumor downstaging (OR 1.11, 95% CI 1.02 to 1.25). The longer time delay was also associated with lower odds of 30-day readmission (OR 0.82, 95% CI 0.70 to 0.92).An nCRT-surgery interval time >8 weeks results in increased odds of pCR, with no evidence of associated increased surgical complications compared with an interval of 6 to 8 weeks. These data support implementation of a lengthened interval after nCRT to optimize the chances of pCR and perhaps add to the possibility of ultimate organ preservation (nonoperative management).

| S-EPMC5014360 | biostudies-other

Systemic inflammatory indices predict tumor response to neoadjuvant chemoradiotherapy for locally advanced rectal cancer.

Project description:Systemic inflammatory responses are associated with the prognosis of patients with colorectal cancer. However, the value in predicting tumor responses to neoadjuvant chemoradiotherapy (nCRT) remains to be elucidated. The current study aimed to investigate the association between systemic inflammatory indices and pathological complete response (pCR). The training and validation cohorts included 225 and 96 patients with locally advanced rectal cancer. The neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio were recorded prior to nCRT and radical surgery. Univariate and multivariate analysis were used to investigate the association between systemic inflammatory indices and pCR. Systemic inflammatory indices prior to or following treatment had no significant association with pCR; however, the percentage change in NLR from pre-nCRT to post-nCRT was associated with a poor response, and a percentage change of >21.5% NLR (P=0.006; OR=0.413; 95% CI=0.22-0.773) was a predictor of poor pCR. Therefore, in rectal cancer, the percentage change in NLR from pre- to post-nCRT was found to be a predictor of poor pCR.

| S-EPMC7400706 | biostudies-literature

Genomic and Transcriptomic Characterisation of Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

Project description:Standard treatment for locally advanced rectal cancer (LARC) is neoadjuvant chemoradiotherapy (NACRT), followed by surgical resection. However, >70% of patients do not achieve a complete pathological response and have higher rates of relapse and death. There are no validated pre- or on-treatment factors that predict response to NACRT besides tumour stage and size. We characterised the response of 33 LARC patients to NACRT, collected tumour samples from patients prior to, during and after NACRT, and performed whole exome, transcriptome and high-depth targeted sequencing. The pre-treatment LARC genome was not predictive of response to NACRT. However, in line with the increasing recognition of microbial influence in cancer, RNA analysis of pre-treatment tumours suggested a greater abundance of Fusobacteria in intermediate and poor responders. In addition, we investigated tumour heterogeneity and evolution in response to NACRT. While matched pre-treatment, on-treatment and post-treatment tumours revealed minimal genome evolution overall, we identified cases in which microsatellite instability developed or was selected for during NACRT. Recent research has suggested a role for adaptive mutability to targeted therapy in colorectal cancer cells. We provide preliminary evidence of selection for mismatch repair deficiency in response to NACRT. Furthermore, pre-NACRT genomic landscapes do not predict treatment response but pre-NACRT microbiome characteristics may be informative.

| S-EPMC7408989 | biostudies-literature

MRI-Based Radiomics Predicts Tumor Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer.

Project description:Background: Conventional methods for predicting treatment response to neoadjuvant chemoradiotherapy (nCRT) in patients with locally advanced rectal cancer (LARC) are limited. Methods: This study retrospectively recruited 134 LARC patients who underwent standard nCRT followed by total mesorectal excision surgery in our institution. Based on pre-operative axial T2-weighted images, machine learning radiomics was performed. A receiver operating characteristic (ROC) curve was performed to test the efficiencies of the predictive model. Results: Among the 134 patients, 32 (23.9%) achieved pathological complete response (pCR), 69 (51.5%) achieved a good response, and 91 (67.9%) achieved down-staging. For prediction of pCR, good-response, and down-staging, the predictive model demonstrated high classification efficiencies, with an AUC value of 0.91 (95% CI: 0.83-0.98), 0.90 (95% CI: 0.83-0.97), and 0.93 (95% CI: 0.87-0.98), respectively. Conclusion: Our machine learning radiomics model showed promise for predicting response to nCRT in patients with LARC. Our predictive model based on the commonly used T2-weighted images on pelvic Magnetic Resonance Imaging (MRI) scans has the potential to be adapted in clinical practice. Novelty and Impact Statements: Methods for predicting the response of the locally advanced rectal cancer (LARC, T3-4, or N+) to neoadjuvant chemoradiotherapy (nCRT) is lacking. In the present study, we developed a new machine learning radiomics method based on T2-weighted images. As a non-invasive tool, this method facilitates prediction performance effectively. It achieves a satisfactory overall diagnostic accuracy for predicting of pCR, good response, and down-staging show an AUC of 0.908, 0.902, and 0.930 in LARC patients, respectively.

| S-EPMC6606732 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data