Introduction
Acute myeloid leukaemia is the most common type of acute leukaemia in the world. Thus, the study of genetic alterations, such as single-nucleotide polymorphisms (SNPs), has contributed to a better understanding of the mechanisms underlying leukaemogenesis, to improve the prognosis and to increase the survival of these patients. However, there is no synthesis of evidence in the literature evaluating the quality of evidence and the risk of bias in the studies such that the results can be translated. Thus, this systematic review protocol aims to assess the impact of SNPs on genes involved in the metabolism of cytarabine and anthracyclines with respect to survival, treatment response and toxicity in patients with AML.
Methods
This systematic review protocol is based on PRISMA guidelines and includes searches in six electronic databases, contact with authors, repositories of clinical trials, and cancer research. Studies published in peer-reviewed journals will be included if they meet the eligibility criteria: (a) samples composed of individuals of any age, of both sexes, with a diagnosis of AML, regardless of the time of diagnosis of disease; (b) participants who have undergone or are undergoing cytarabine- and anthracycline-associated chemotherapy or cytarabine-only chemotherapy; and (c) in vivo studies. Studies that include patients with promyelocytic leukaemia (Fab type 3) will be excluded because this disease has different treatment. The process of study selection, data extraction, and evaluation/synthesis will be performed in duplicate. Assessment of methodological quality and risk of bias will be performed using the Cochrane Risk of Bias Tool for randomized clinical studies and the Downs-Black Checklist for cohort and case-control studies. The synthesis of evidence will include the level of evidence based on the GRADE protocol. A meta-analysis of the association between SNPs and outcomes may be performed based on Cochrane guidelines.
Discussion
It is expected that clinical decisions for AML patients will consider evidence-based practices to contribute to better patient management. In this way, we will be able to define how to treat patients with AML to improve their survival and quality of life.
Systematic review registration
PROSPERO
CRD42018100750
Electronic supplementary material
The online version of this article (10.1186/s13643-019-1011-y) contains supplementary material, which is available to authorized users.
Background:
Colorectal cancer (CRC) is the second most prevalent cancer in the world when
nonmelanoma skin cases are not considered. Different epigenetic mechanisms play a role in the development
of cancer. Noncoding RNAs (ncRNAs) are RNA molecules transcribed from noncoding regions of the
genome. These are divided into sncRNAs (small noncoding RNAs: <200 nucleotides - including miRNAs
[microRNAs], siRNAs [small interfering RNAs], piRNAs [piwi-interacting RNAs], snoRNAs [small
nucleolar RNAs]) and lncRNAs (long noncoding RNAs: >200 nucleotides – includingcircular RNAs
[circRNAs]). NcRNAs can act as oncogenes or as tumor suppressor genes in CRC and are potential biomarkers
of diagnosis, with possible clinical implications.
Objective:
This article aims to make a general review around all types of non-coding RNAs and influence in
colorectal cancer, focus in biomarkesof CRC and their possible applications in clinical practice, as well as
review their biogenesis and functions. Furthermore, we seek to summarize possible databases available for new
searches and studies that require sequence annotation, comparison sequences and target prediction for ncRNAs with the
hope ofgathering information that can aid in the process of understanding and translating the use of ncRNAs into clinical
practice.
Cetuximab, an anti-EGFR monoclonal antibody, has shown benefits when combined with the standard chemotherapy protocol for treating metastatic colorectal cancer (mCRC) in patients with wild-type Kras, either as the first-line or subsequent-line treatment. The most frequent profiles of toxicity are hematologic (8% grade 3 and 5% grade 4), dermatologic (24% grade 3 and 2% grade 4), acneiform exanthem (17% grade 3 and 0% grade 4) and diarrhea (10% grade 3 and 1% grade 4), which are critical for the maintenance of therapeutic regimens until disease progression. Thus, this study aims to report the cases of two patients with mCRC undergoing FOLFOX protocol associated with Cetuximab as first-line for metastatic disease. Both patients were male, older and with good clinical performance (ECOG 0.1). The subjects were followed for five years. Radiological complete responses were observed, encouraging continuity of care in Long Term Use (LTU). Clinical and radiological outcomes were unequivocally represented by complete responses, associated with acceptable and manageable tolerability profiles, culminating in overall survival (OS) over 60 months (5 years) from diagnosis. Thus, the data reported in this case series corroborate the data from current studies demonstrating benefits of anti-EGFR therapy in selected populations of patients with wild-type Kras, as first shown in OPUS study and more recently in the CALGB/ SWOG 80405 study, emphasizing that treatment of mCRC with new oncogenetically guided approaches can significantly increase OS and tumor regression rates at LTU protocols.
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