detection-circulating-microrna-custom-panel-patients-with-metastatic

Detection of a Circulating MicroRNA Custom Panel in Patients with Metastatic Colorectal Cancer

There is increasing interest in liquid biopsy for cancer diagnosis, prognosis and therapeutic monitoring, creating the need for reliable and useful ...

Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS

Erratum to "Systematic versus on-demand early palliative care: A randomised clinical trial assessing quality of care and treatment aggressiveness near the end of life" [Eur J Cancer 69 (2016) 110-118].

There is evidence of a different response to treatment with regard to the primary tumor localization (right-sided or left-sided) in patients with metastatic colorectal cancer (mCRC). We analyzed the different outcomes and biomolecular characteristics in relation to tumor localization in 122 of the 370 patients with metastatic colorectal cancer enrolled onto the phase III prospective multicenter "Italian Trial in Advanced Colorectal Cancer (ITACa)", randomized to receive first-line chemotherapy (CT) or CT plus bevacizumab (CT + B). RAS and BRAF mutations; baseline expression levels of circulating vascular endothelial growth factor (VEGF), endothelial nitric oxide synthase (eNOS), cyclooxygenase-2 (COX2), ephrin type-B receptor 4 (EPHB4), hypoxia-inducible factor 1-alpha (HIF-1α), lactate dehydrogenase (LDH), and high-sensitivity C reactive protein (hs-CRP); and inflammatory indexes such as the neutrophil-to-lymphocyte ratio, platelet-lymphocyte rate and systemic immune-inflammation index were evaluated. Patients with right-sided tumors showed a longer median progression-free survival in the CT + B arm than in the CT group (12.6 vs. 9.0 months, respectively, p = 0.017). Baseline inflammatory indexes were significantly higher in left-sided tumors, whereas eNOS and EPHB4 expression was significantly higher and BRAF mutation more frequent in right-sided tumors. Our data suggest a greater efficacy of the CT + B combination in right-sided mCRC, which might be attributable to the lower inflammatory status and higher expression of pro-angiogenic factors that appear to characterize these tumors.

Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy.

The ITACa trial was designed to define the role of cetuximab (Cet) and bevacizumab (Bev) in combination with standard chemotherapy (CT, FOLFIRI or FOLFOX4) as first- and second-line treatment in metastatic colorectal cancer. All patients with WT KRAS tumors who had been enrolled in the first-line trial were randomized onto two independent second-line trials: CT or CT + Cet (study 2A) and CT + Bev or CT + Bev + Cet (study 2B). Patients with mutated KRAS were not eligible for randomization and were treated with CT alone (study 2A) or CT + Bev (study 2B). The primary endpoint was progression-free survival (PFS). 48 and 56 KRAS WT patients were randomized while 31 and 40 KRAS mutated patients were treated without randomization. Study 2A: median PFS was 3.4 (95%CI 2.3-4.6) and 6.2 (95%CI 4.3-7.8) months for the CT and CT + Cet arms, respectively, with a hazard ratio (HR) = 0.64 (95%CI 0.35-1.16, p = 0.144). Study 2B: median PFS was 7.7 (95%CI 4.1-10.1) and 4.9 (95%CI 3.2-7.0) months for CT + Bev and CT + Cet + Bev arms, respectively, with a HR = 1.31 (95%CI 0.76-2.26, p = 0.330). Notwithstanding limitations due to the small sample size, among patients with WT KRAS the addition of Cet to second-line CT increased PFS, whereas the addition of Cet to CT + Bev was associated with worse PFS.

Impact of second-line cetuximab-containing therapy in patients with KRAS wild-type metastatic colorectal cancer: results from the ITACa randomized clinical trial.

Targeting angiogenesis in the treatment of colorectal cancer (CRC) is a common strategy, for which potential predictive biomarkers have been studied. miRNAs are small non-coding RNAs involved in several processes including the angiogenic pathway. They are very stable in biological fluids, which turns them into potential circulating biomarkers. In this study, we considered a case series of patients with metastatic (m) CRC treated with a bevacizumab (B)-based treatment, enrolled in the prospective multicentric Italian Trial in Advanced Colorectal Cancer (ITACa). We then analyzed a panel of circulating miRNAs in relation to the patient outcome. In multivariate analysis, circulating basal levels of hsa-miR-20b-5p, hsa-miR-29b-3p and hsa-miR-155-5p resulted in being significantly associated with progression-free survival (PFS) (p = 0.027, p = 0.034 and p = 0.039, respectively) and overall survival (OS) (p = 0.044, p = 0.024 and p = 0.032, respectively). We also observed that an increase in hsa-miR-155-5p at the first clinical evaluation was significantly associated with shorter PFS (HR 3.03 (95% CI 1.06-9.09), p = 0.040) and OS (HR 3.45 (95% CI 1.18-10.00), p = 0.024), with PFS and OS of 9.5 (95% CI 6.8-18.7) and 15.9 (95% CI 8.4-not reached), respectively, in patients with an increase ≥30% of hsa-miR-155-5p and 22.3 (95% CI 10.2-25.5) and 42.9 (24.8-not reached) months, respectively, in patients without such increase. In conclusion, our results highlight the potential usefulness of circulating basal levels of hsa-miR-20b-5p, hsa-miR-29b-3p and hsa-miR-155-5p in predicting the outcome of patients with mCRC treated with B. In addition, the variation of circulating hsa-miR-155-5p could also be indicative of the patient survival.

Circulating Plasma Levels of miR-20b, miR-29b and miR-155 as Predictors of Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer.

To investigate early changes in tumour perfusion parameters by dynamic contrast-enhanced ultrasonography (D-CEUS) and to identify any correlation with survival and tumour response in patients with metastatic colorectal cancer (CRC) treated with bevacizumab (B).

Dynamic contrast-enhanced ultrasonography (D-CEUS) for the early prediction of bevacizumab efficacy in patients with metastatic colorectal cancer.

Tumor microenvironment (TME) includes many factors such as tumor associated inflammatory cells, vessels, and lymphocytes, as well as different signaling molecules and extracellular matrix components. These aspects can be de-regulated and consequently lead to a worsening of cancer progression. In recent years an association between the scaffolding protein Na/H exchanger regulatory factor 1 (NHERF1) and tumor microenvironment changes in breast cancer (BC) has been reported.

NHERF1 and tumor microenvironment: a new scene in invasive breast carcinoma.

Genomic studies have shown that the androgen receptor (AR) pathway plays an important role in some breast cancer subtypes. However few data are present on the concordance between AR expression in primary tumors and metastases. We investigated AR expression by using immunohistochemistry (IHC) in 164 primary tumors and 83 metastases, to explore its distribution in the different tumor subtypes and its concordance between the two sample types and according to sampling time. AR was more highly expressed in luminal A and B than HER2-positive and triple negative primary tumors. A similar distribution was found in metastases, and the concordance of AR expression between primary tumors and metastases was greater than 60%. No association between sampling time and AR expression was observed. We found a good concordance of AR expression between primary tumor and metastasis, but the variability remains high between the two types of specimens, regardless of the variation in sampling time. For this reason, if used for treatment decisions, AR evaluation should be repeated in each patient whenever a new biopsy is performed, as commonly done for the other breast cancer biomarkers.

Androgen Receptor Expression in Breast Cancer: What Differences Between Primary Tumor and Metastases?

The aim of this study was to investigate the role of pre-treatment aspartate aminotransferase-lynphocyte ratio (ALRI) as a predictor of prognosis and treatment efficacy in patients with metastatic colorectal cancer (mCRC) enrolled in the prospective multicenter randomized ITACa (Italian Trial in Advanced Colorectal Cancer) trial to receive first-line chemotherapy (CT) + bevacizumab (B) or CT alone.

Prognostic role of aspartate aminotransferase-lymphocyte ratio index in patients with metastatic colorectal cancer: results from the randomized ITACa trial.

So far, no randomized trial or meta-analysis has been conducted on overall survival (OS) and recurrence-free survival (RFS) factors in patients treated with radiofrequency ablation (RFA) alone. The purpose of this meta-analysis was to evaluate prognostic factors of OS and RFS in patients treated with RFA.

Radiofrequency ablation of hepatocellular carcinoma: a meta-analysis of overall survival and recurrence-free survival.

Early palliative care (EPC) has shown a positive impact on quality of life (QoL), quality of care, and healthcare costs. We evaluated such effects in patients with advanced gastric cancer.

Systematic vs. on-demand early palliative care in gastric cancer patients: a randomized clinical trial assessing patient and healthcare service outcomes.

Tumor infiltrating lymphocytes (TILs) are widely considered a key sign of the immune interaction between host and tumor, and potentially prognostic biomarkers of good or bad outcome in many cancers, included invasive breast cancer (BC). However, results about the association between TIL typology, location and BC prognosis, are controversial. The aim of the study was to evaluated the prognostic significance of TIL subtypes (CD4+, CD8+, FOXP3+ T cells) and their location (stromal "s" and intratumoral "i" CD4+ and CD8+) in BC patients, focusing on the association between these markers and immunocheckpoint molecules such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death ligand 1 (PD-L1) and its receptor (PD-1).

Article	Year
Erratum to "Systematic versus on-demand early palliative care: A randomised clinical trial assessing quality of care and treatment aggressiveness near the end of life" [Eur J Cancer 69 (2016... European journal of cancer (Oxford, England : 1990)\| PubMed ID: 28027830	2017
Right- vs. Left-Sided Metastatic Colorectal Cancer: Differences in Tumor Biology and Bevacizumab Efficacy. International journal of molecular sciences\| PubMed ID: 28598398	2017
Impact of second-line cetuximab-containing therapy in patients with KRAS wild-type metastatic colorectal cancer: results from the ITACa randomized clinical trial. Scientific reports\| PubMed ID: 28874797	2017
Circulating Plasma Levels of miR-20b, miR-29b and miR-155 as Predictors of Bevacizumab Efficacy in Patients with Metastatic Colorectal Cancer. International journal of molecular sciences\| PubMed ID: 29361687	2018
Dynamic contrast-enhanced ultrasonography (D-CEUS) for the early prediction of bevacizumab efficacy in patients with metastatic colorectal cancer. European radiology\| PubMed ID: 29417252	2018
NHERF1 and tumor microenvironment: a new scene in invasive breast carcinoma. Journal of experimental & clinical cancer research : CR\| PubMed ID: 29716631	2018
Androgen Receptor Expression in Breast Cancer: What Differences Between Primary Tumor and Metastases? Translational oncology\| PubMed ID: 29890379	2018
Prognostic role of aspartate aminotransferase-lymphocyte ratio index in patients with metastatic colorectal cancer: results from the randomized ITACa trial. OncoTargets and therapy\| PubMed ID: 30214231	2018
Radiofrequency ablation of hepatocellular carcinoma: a meta-analysis of overall survival and recurrence-free survival. OncoTargets and therapy\| PubMed ID: 30323628	2018
Systematic vs. on-demand early palliative care in gastric cancer patients: a randomized clinical trial assessing patient and healthcare service outcomes. Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer\| PubMed ID: 30357555	2018
Intratumoral, rather than stromal, CD8+ T cells could be a potential negative prognostic marker in invasive breast cancer patients. Translational oncology\| PubMed ID: 30682679	2019

Emanuela Scarpi

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