scholarly journals The Role of Micro-RNAs and Circulating Tumor Markers as Predictors of Response to Neoadjuvant Therapy in Locally Advanced Rectal Cancer

2020 ◽  
Vol 21 (19) ◽  
pp. 7040 ◽  
Author(s):  
Fatima Domenica Elisa De Palma ◽  
Gaetano Luglio ◽  
Francesca Paola Tropeano ◽  
Gianluca Pagano ◽  
Maria D’Armiento ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Clinical Decision Making ◽  
Locally Advanced ◽  
Therapy Response ◽  
Predictive Biomarkers ◽  
Advanced Rectal Cancer ◽  
Clinical Decision ◽  
Locally Advanced Rectal Cancer ◽  
Specific Expression ◽  
Micro Rnas

The response to neoadjuvant chemoradiation (nCRT) is a critical step in the management of locally advanced rectal cancer (LARC) patients. Only a minority of LARC patients responds completely to neoadjuvant treatments, thus avoiding invasive radical surgical resection. Moreover, toxic side effects can adversely affect patients’ survival. The difficulty in separating in advances responder from non-responder patients affected by LARC highlights the need for valid biomarkers that guide clinical decision-making. In this context, microRNAs (miRNAs) seem to be promising candidates for predicting LARC prognosis and/or therapy response, particularly due to their stability, facile detection, and disease-specific expression in human tissues, blood, serum, or urine. Although a considerable number of studies involving potential miRNA predictors to nCRT have been conducted over the years, to date, the identification of the perfect miRNA signatures or single miRNA, as well as their use in the clinical practice, is still representing a challenge for the management of LARC patients. In this review, we will first introduce LARC and its difficult management. Then, we will trace the scientific history and the key obstacles for the identification of specific miRNAs that predict responsiveness to nCRT. There is a high potential to identify non-invasive biomarkers that circulate in the human bloodstream and that might indicate the LARC patients who benefit from the watch-and-wait approach. For this, we will critically evaluate recent advances dealing with cell-free nucleic acids including miRNAs and circulating tumor cells as prognostic or predictive biomarkers.

scholarly journals Predictive Biomarkers to Chemoradiation in Locally Advanced Rectal Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-10 ◽  
Author(s):  
Raquel Conde-Muíño ◽  
Marta Cuadros ◽  
Natalia Zambudio ◽  
Inmaculada Segura-Jiménez ◽  
Carlos Cano ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Rectal Adenocarcinoma ◽  
Surgical Techniques ◽  
Predictive Biomarkers ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Neoadjuvant Chemoradiation ◽  
High Local Recurrence Rate

There has been a high local recurrence rate in rectal cancer. Besides improvements in surgical techniques, both neoadjuvant short-course radiotherapy and long-course chemoradiation improve oncological results. Approximately 40–60% of rectal cancer patients treated with neoadjuvant chemoradiation achieve some degree of pathologic response. However, there is no effective method of predicting which patients will respond to neoadjuvant treatment. Recent studies have evaluated the potential of genetic biomarkers to predict outcome in locally advanced rectal adenocarcinoma treated with neoadjuvant chemoradiation. The articles produced by the PubMed search were reviewed for those specifically addressing a genetic profile’s ability to predict response to neoadjuvant treatment in rectal cancer. Although tissue gene microarray profiling has led to promising data in cancer, to date, none of the identified signatures or molecular markers in locally advanced rectal cancer has been successfully validated as a diagnostic or prognostic tool applicable to routine clinical practice.

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.

228. Predicting neoadjuvant therapy response in locally advanced rectal cancer using texture features

2018 ◽  
Vol 56 ◽  
pp. 203
Author(s):  
S. Mazzetti ◽  
V. Giannini ◽  
A. Di Dia ◽  
C. Bracco ◽  
S. Bresciani ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Therapy Response ◽  
Texture Features ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

Current possibilities of predicting the therapeutic response to neoadjuvant chemoradiotherapy in rectal cancer

2020 ◽  
Vol 74 (5) ◽  
pp. 393-403
Author(s):  
Filip Pazdírek ◽  
Marek Minárik ◽  
Lucie Benešová ◽  
Jiří Hoch ◽  
Radka Lohynská
Keyword(s):  
Rectal Cancer ◽  
Therapeutic Response ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Therapy Response ◽  
Standard Of Care ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Dna And Rna ◽  
Post Radiation

Neoadjuvant chemotherapy in combination with radiation is currently the standard of care for patients with locally advanced rectal cancer. The main purpose of the treatment is to reduce the risk of recurrence, however at the same time it may be accompanied by severe adverse effects due to post-radiation pelvic damage. An effort towards finding markers allowing the prediction of the therapy response has been undertaken by many groups. In this review we have performed a literature search to identify the main studies directed at the use of clinical, radiological, immunological and molecular (protein, DNA and RNA) markers. We present a summary for each group with an overall conclusion that a certain level of ambiguity and disunity in interpretation of the results currently exists among the reported findings. Apparently, even in the most promising direction of circulating molecular bio­markers further work is needed before a clinical utility can be established.

16. Predicting neoadjuvant therapy response in locally advanced rectal cancer using texture features

2018 ◽  
Vol 56 ◽  
pp. 70
Author(s):  
S. Mazzetti ◽  
V. Giannini ◽  
A. Di Dia ◽  
C. Bracco ◽  
S. Bresciani ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Neoadjuvant Therapy ◽  
Locally Advanced ◽  
Therapy Response ◽  
Texture Features ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

scholarly journals Magnetic resonance imaging evaluation in neoadjuvant therapy of locally advanced rectal cancer: a systematic review

2017 ◽  
Vol 51 (3) ◽  
pp. 252-262 ◽  
Author(s):  
Roberta Fusco ◽  
Mario Petrillo ◽  
Vincenza Granata ◽  
Salvatore Filice ◽  
Mario Sansone ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Diagnostic Accuracy ◽  
Locally Advanced ◽  
Therapy Response ◽  
Roc Curves ◽  
Response Assessment ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer ◽  
Dce Mri ◽  
Pet Ct

Abstract Background The aim of the study was to present an update concerning several imaging modalities in diagnosis, staging and pre-surgery treatment response assessment in locally advanced rectal cancer (LARC). Modalities include: traditional morphological magnetic resonance imaging (MRI), functional MRI such as dynamic contrast enhanced MRI (DCE-MRI) and diffusion weighted imaging (DWI). A systematic review about the diagnostic accuracy in neoadjuvant therapy response assessment of MRI, DCE-MRI, DWI and Positron Emission Tomography/Computed Tomography (PET/CT) has been also reported. Methods Several electronic databases were searched including PubMed, Scopus, Web of Science, and Google Scholar. All the studies included in this review reported findings about therapy response assessment in LARC by means of MRI, DCE-MRI, DWI and PET/CT with details about diagnostic accuracy, true and false negatives, true and false positives. Forest plot and receiver operating characteristic (ROC) curves analysis were performed. Risk of bias and the applicability at study level were calculated. Results Twenty-five papers were identified. ROC curves analysis demonstrated that multimodal imaging integrating morphological and functional MRI features had the best accuracy both in term of sensitivity and specificity to evaluate preoperative therapy response in LARC. DCE-MRI following to PET/CT showed high diagnostic accuracy and their results are also more reliable than conventional MRI and DWI alone. Conclusions Morphological MRI is the modality of choice for rectal cancer staging permitting a correct assessment of the disease extent, of the lymph node involvement, of the mesorectal fascia and of the sphincter complex for surgical planning. Multimodal imaging and functional DCE-MRI may also help in the assessment of treatment response allowing to guide the surgeon versus conservative strategies and/or tailored approach such as “wait and see” policy.

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