Dataset Information

C-Reactive Protein as Predictive Biomarker for Response to Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer: A Retrospective Study.

ABSTRACT: The standard of care for the treatment of locally advanced rectal cancer is neoadjuvant chemoradiotherapy (nCRT) followed by surgery, but complete response rates are reduced. To find predictive biomarkers of response to therapy, we conducted a retrospective study evaluating blood biomarkers before nCRT. Hemoglobin (Hg), C-reactive protein (CRP), platelets, carcinoembryonic antigen, carbohydrate antigen 19.9 levels, and neutrophil/lymphocyte ratio were obtained from 171 rectal cancer patients before nCRT. Patients were classified as responders (Ryan 0-1; ycT0N0), 59.6% (n = 102), or nonresponders (Ryan 2-3), 40.3% (n = 69), in accordance with the Ryan classification. A logistic regression using prognostic pretreatment factors identified CRP ≤ 3.5 (OR = 0.05; 95%CI: 0.01-0.21) as a strong independent predictor of response to treatment. Multivariate analysis showed that CRP was an independent predictor of disease-free survival (DFS) (HR = 5.48; 95%CI: 1.54-19.48) and overall survival (HR = 6.10; 95%CI 1.27-29.33) in patients treated with nCRT. Platelets were an independent predictor of DFS (HR = 3.068; 95%CI: 1.29-7.30) and OS (HR= 4.65; 95%CI: 1.66-13.05) and Hg was revealed to be an independent predictor of DFS (HR = 0.37; 95%CI: 0.15-0.90) in rectal cancer patients treated with nCRT. The lower expression of CRP is independently associated with an improved response to nCRT, DFS, and OS.

SUBMITTER: Aires F

PROVIDER: S-EPMC8833484 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

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C-Reactive Protein as Predictive Biomarker for Response to Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer: A Retrospective Study.

Aires Fátima F Rodrigues Darlene D Lamas María Piñeiro MP Herdeiro Maria Teresa MT Figueiras Adolfo A Oliveira Maria José MJ Marques Margarida M Pinto Ana Teresa AT

Cancers 20220119 3

The standard of care for the treatment of locally advanced rectal cancer is neoadjuvant chemoradiotherapy (nCRT) followed by surgery, but complete response rates are reduced. To find predictive biomarkers of response to therapy, we conducted a retrospective study evaluating blood biomarkers before nCRT. Hemoglobin (Hg), C-reactive protein (CRP), platelets, carcinoembryonic antigen, carbohydrate antigen 19.9 levels, and neutrophil/lymphocyte ratio were obtained from 171 rectal cancer patients bef ...[more]

PMID: 35158759

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Project description:BackgroundColorectal cancer is the third most common and the fourth most lethal cancer in the world. In the majority of cases, patients are diagnosed at an advanced stage or even metastatic, thus explaining the high mortality. The standard treatment for patients with locally advanced non-metastatic rectal cancer is neoadjuvant radio-chemotherapy (NRCT) with 5-fluorouracil (5-FU) followed by surgery, but the resistance rate to this treatment remains high with approximately 30% of non-responders. The lack of evidence available in clinical practice to predict NRCT resistance to 5-FU and to guide clinical practice therefore encourages the search for biomarkers of this resistance.MethodsFrom twenty-three formalin-fixed paraffin-embedded (FFPE) biopsies performed before NRCT with 5-FU of locally advanced non-metastatic rectal cancer patients, we extracted and analysed the tumor proteome of these patients. From clinical data, we were able to classify the twenty-three patients in our cohort into three treatment response groups: non-responders (NR), partial responders (PR) and total responders (TR), and to compare the proteomes of these different groups.ResultsWe have highlighted 384 differentially abundant proteins between NR and PR, 248 between NR and TR and 417 between PR and TR. Among these proteins, we have identified many differentially abundant proteins identified as having a role in cancer (IFIT1, FASTKD2, PIP4K2B, ARID1B, SLC25A33: overexpressed in TR; CALD1, CPA3, B3GALT5, CD177, RIPK1: overexpressed in NR). We have also identified that DPYD, the main degradation enzyme of 5-FU, was overexpressed in NR, as well as several ribosomal and mitochondrial proteins also overexpressed in NR. Data are available via ProteomeXchange with identifier PXD008440.ConclusionsFrom these retrospective study, we implemented a protein extraction protocol from FFPE biopsy to highlight protein differences between different response groups to RCTN with 5-FU in patients with locally advanced non-metastatic rectal cancer. These results will pave the way for a larger cohort for better sensitivity and specificity of the signature to guide decisions in the choice of treatment.

Project description:BackgroundPatients with locally advanced rectal cancer (LARC) have an improved prognosis if achieved a pathological complete response (pCR) on account of neoadjuvant chemoradiation therapy (nCRT). However, the proportion of patients achieving pCR is only 8-24%. The purpose of this study was to explore whether the addition of consolidation chemotherapy to nCRT could improve pCR rate in patients with LARC.Materials and methodsThe subjects were 144 individuals with clinical stage II (T3-4, N0) or III (any T, N1-2) LARC who had received neoadjuvant CRT followed by total mesorectal excision (TME). Eighty-three patients in the consolidation chemotherapy group received two cycles XELOX between CRT and TME, while 61 patients in the standard treatment group without consolidation chemotherapy. The pCR (ypT0N0), tumor downstaging (ypT0-2N0) after TME and adverse events (AEs) during and post treatment were compared between the treatment groups using multivariable logistic regression analysis. To adjust the unbalanced variables for the primary endpoint, logistic regression analysis and stratified analysis were performed.ResultsThe consolidation chemotherapy group improved pCR rate (19.3% vs 4.9%, p = 0.01) and tumor downstaging rate (45.8% vs 24.6%, p = 0.009) compared to the standard treatment group. After adjustment for clinical tumor stage, clinical nodal stage and time interval to surgery, patients with consolidation chemotherapy were more likely to reach pCR (adjusted odds ratio 4.91, 95% CI [1.01-23.79], p = 0.048). AEs during and post treatment in the two groups were 54.1% vs 49.3% (p = 0.57), respectively. In addition, the incidence of any grade 1-2 AEs in the two groups was 93.4% vs 95.1% (p = 0.93), while the incidence of grade 3 AEs was 1.6% versus 2.4% (p = 0.74), respectively. No grade 4 AEs occurred in two groups.ConclusionsThe addition of neoadjuvant consolidation chemotherapy after CRT significantly increased the pCR rate and did not increase the AEs during and post treatment and in patients with LARC.

Dataset Information

C-Reactive Protein as Predictive Biomarker for Response to Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer: A Retrospective Study.

Publications

C-Reactive Protein as Predictive Biomarker for Response to Chemoradiotherapy in Patients with Locally Advanced Rectal Cancer: A Retrospective Study.

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