scholarly journals Validation of Gene Expression-Based Predictive Biomarkers for Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer

Cancers ◽  
2021 ◽  
Vol 13 (18) ◽  
pp. 4642
Author(s):  
Tomoyuki Momma ◽  
Hirokazu Okayama ◽  
Yasuyuki Kanke ◽  
Satoshi Fukai ◽  
Hisashi Onozawa ◽  
...  
Keyword(s):  
Gene Expression ◽  
Rectal Cancer ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Predictive Biomarkers ◽  
Advanced Rectal Cancer ◽  
Gene Signature ◽  
Locally Advanced Rectal Cancer ◽  
Predictive Values

Background: Neoadjuvant chemoradiotherapy (nCRT) followed by surgery is widely used for patients with locally advanced rectal cancer. However, response to nCRT varies substantially among patients, highlighting the need for predictive biomarkers that can distinguish non-responsive from responsive patients before nCRT. This study aimed to build novel multi-gene assays for predicting nCRT response, and to validate our signature and previously-reported signatures in multiple independent cohorts. Methods: Three microarray datasets of pre-therapeutic biopsies containing a total of 61 non-responders and 53 responders were used as the discovery cohorts to screen for genes that were consistently associated with nCRT response. The predictive values of signatures were tested in a meta-analysis using six independent datasets as the validation cohorts, consisted of a total of 176 non-responders and 99 responders. Results: We identified four genes, including BRCA1, GPR110, TNIK, and WDR4 in the discovery cohorts. Although our 4-gene signature and nine published signatures were evaluated, they were unable to predict nCRT response in the validation cohorts. Conclusions: Although this is one of the largest studies addressing the validity of gene expression-based classifiers using pre-treatment biopsies from patients with rectal cancer, our findings do not support their clinically meaningful values to be predictive of nCRT response.

Predicting the pathologic complete regression with hematologic markers during neoadjuvant chemoradiotherapy in the locally advanced rectal cancer.

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 583-583
Author(s):  
Jae-Sung Kim ◽  
Joo Ho Lee ◽  
Changhoon Song
Keyword(s):  
Rectal Cancer ◽  
Univariate Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
P Value ◽  
Complete Regression ◽  
Operating Characteristics ◽  
Predictive Values

583 Background: The present study aimed to evaluate the hematologic markers for predicting the pathologic complete regression during and after neoadjuvant chemoradiotherapy (CRT) in patients with locally advanced rectal cancer. Methods: Total 297 patients with rectal cancer underwent neoadjuvant CRT followed by surgical resection and performed complete blood counts (CBC) serially during and after CRT. The timepoints of CBC were before CRT (pre-), three weeks after the day of starting CRT (intra-), and four weeks after CRT (post-). We calculated the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte (NLR), derived neutrophil-to-lymphocyte (dNLR) using the serial CBC test. The ratio of change in PLR (cPLR), NLR (cNLR), and dNLR (cdNLR) was calculated as the change of value/pre-value. Chi-square and T-test for univariate analysis and multivariate logistic regression were performed to identify the significant predictor for pCR. Receiver operating characteristics (ROC) analysis was used to compare the predictive values. Results: The overall rate of pCR was 15.9%. The Pre-Hb, pre-NLR, intra-PLR, intra-NLR, intra-cPLR, intra-cNLR, post-WBC, post-Hb, and post-cPLR were significantly different between patients with pCR and no pCR. In the multivariate logstic regression, pre-Hb (OR 1.456 p-value .026), intra-cPLR (OR 4.949, p-value < .001), post-WBC (OR 0.664, p-value .008), and post-PLR (OR 1.011 p-value .001) were significant predictors for pCR. In the comparison of ROCs, intra-cPLR was the most accurate predictor for pCR among the hematologic variables (AUC = 0.74, p ≤ .001). Conclusions: Change of PLR during neoadjuvant CRT is the clinically applicable and significant predictor for pCR with high negative predictive value in the patients with LRC.

scholarly journals Adjuvant Second-Dose Chemotherapy before Surgery for Patients with Locally Advanced Rectal Malignancy Is Not Beneficial: A Systematic Review and Meta-Analysis

2017 ◽  
Vol 2017 ◽  
pp. 1-8
Author(s):  
Min Chen ◽  
Xue Song ◽  
Liang-zhou Chen ◽  
Lin Xu ◽  
Yi-pu Lu ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Combination Chemotherapy ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Preoperative Chemoradiotherapy ◽  
Locally Advanced Rectal Cancer ◽  
Cochrane Library ◽  
Controlled Trials

Background. Preoperative chemoradiotherapy is the standard treatment for patients with locally advanced rectal cancer, although tumor responses vary widely; some patients may achieve a pathologic complete response rate (pCR) after chemoradiotherapy. Controversy exists with regard to the efficacy of different preoperative combination chemotherapy regimens and neoadjuvant chemoradiotherapy, compared with chemoradiotherapy alone. Methods. PubMed, the Cochrane Library, and Embase databases were searched for comparative studies of patients with locally advanced rectal cancer that were published between January 1991 and January 2016. Efficacies of different preoperative combination chemotherapy regimens and neoadjuvant chemoradiotherapy (group A) were compared with chemoradiotherapy alone (group B) in a meta-analysis using Review Manager v5.2. Results. Three prospective randomized controlled trials and two prospective nonrandomized controlled trials comprising 444 cases were eligible for analysis. No significant difference was detected in the rate of pCR (50/223, 22.4% versus 35/223, 15.7%; relative risk, RR: 1.42 [95% confidence interval, CI: 0.97–2.09], p=0.07) between the two groups. The rate of tumor regression was similar for both groups (122/203, 60.1% versus 111/203, 54.7%; RR: 1.11 [95% CI: 0.94–1.29], p=0.22). Conclusions. Adjuvant chemotherapy with preoperative chemoradiotherapy did not significantly improve the rate of pCR nor the rate of T and N downstaging.

scholarly journals Effect of Neoadjuvant Chemoradiotherapy with Capecitabine versus Fluorouracil for Locally Advanced Rectal Cancer: A Meta-Analysis

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Guo-Chen Liu ◽  
Jun-Ping Yan ◽  
Qing He ◽  
Xin An ◽  
Zhi-Zhong Pan ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Meta Analysis ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Biomedical Literature ◽  
Ovid Medline ◽  
Hand Foot Syndrome

A meta-analysis was carried out to compare the efficacy and safety of capecitabine plus radiation with 5-fluorouracil (5-FU) plus radiotherapy (RT) as neoadjuvant treatment in locally advanced rectal cancer (LARC). We searched the Cochrane database, Ovid, Medline, Embase, ISI databases, and Chinese Biomedical Literature Database between January 1998 and October 2014. Trials of capecitabine compared with 5-FU plus RT as neoadjuvant treatment for LARC were considered for inclusion. RevMan software was used to analyze these data. Nine trials were included in this meta-analysis, which covered a total of 3141 patients. The meta-analysis showed that capecitabine group had statistically significant better pCR rates (OR, 1.34; 95% CI, 1.10–1.64;P=0.003), T downstaging rates (OR, 1.58; 95% CI, 1.22–2.06;P=0.0007), N downstaging rates (OR, 2.06; 95% CI, 1.34–3.16;P=0.001), less distant metastasis (OR, 0.63; 95% CI, 0.44–0.88;P=0.007), and lowered leucocytes (OR, 0.25; 95% CI, 0.11–0.54;P=0.0005), but with higher incidence of hand-foot syndrome (HFS) (OR, 4.43; 95% CI, 1.59–12.33;P=0.004). Capecitabine was more efficient than 5-FU in terms of tumor response in neoadjuvant treatment for patients with LARC and favourably low toxicity with the exception of HFS.

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