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Acta Haematologica 2020The treatment of chronic myeloid leukaemia (CML) requires quantitative polymerase chain reaction (qPCR) to monitor BCR-ABL1 in International Scale (IS). Some normal...
The treatment of chronic myeloid leukaemia (CML) requires quantitative polymerase chain reaction (qPCR) to monitor BCR-ABL1 in International Scale (IS). Some normal subjects were found to harbour BCR-ABL1. We performed a systematic review on normal subjects harbouring BCR-ABL1. A literature search was done on July 16, 2017 using EBSCOhost Research Databases interface and Western Pacific Region Index Medicus. Two authors selected the studies, extracted the data, and evaluated the quality of studies using the modified Appraisal Tool for Cross-Sectional Studies independently. The outcomes were prevalence, level of BCR-ABL1IS, proportion, and time of progression to CML. The initial search returned 4,770 studies. Eleven studies, all having used convenient sampling, were included, with total of 1,360 subjects. Ten studies used qualitative PCR and one used qPCR (not IS). The mean prevalence of M-BCR was 5.9, 15.5, and 15.9% in cord blood/newborns/infants (CB/NB/I) (n = 170), children (n = 90), and adults (n = 454), respectively, while m-BCR was 15, 26.9, and 23.1% in CB/NB/I (n = 786), children (n = 67), and adults (n = 208), respectively. No study reported the proportion and time of progression to CML. Nine studies were graded as moderate quality, one study as poor quality, and one study as unacceptable. The result of the studies could neither be inferred to the general normal population nor compared. Follow-up data were scarce.
Topics: Acute Disease; Blast Crisis; Chronic Disease; Databases, Factual; Fusion Proteins, bcr-abl; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Philadelphia Chromosome
PubMed: 31401626
DOI: 10.1159/000501146 -
ESMO Open Apr 2021Approved first-line treatments for patients with BRAF V600-mutant advanced melanoma include nivolumab (a programmed cell death protein 1 inhibitor) plus ipilimumab (a...
BACKGROUND
Approved first-line treatments for patients with BRAF V600-mutant advanced melanoma include nivolumab (a programmed cell death protein 1 inhibitor) plus ipilimumab (a cytotoxic T lymphocyte antigen-4 inhibitor; NIVO+IPI) and the BRAF/MEK inhibitors dabrafenib plus trametinib (DAB+TRAM), encorafenib plus binimetinib (ENCO+BINI), and vemurafenib plus cobimetinib (VEM+COBI). Results from prospective randomized clinical trials (RCTs) comparing these treatments have not yet been reported. This analysis evaluated the relative efficacy and safety of NIVO+IPI versus DAB+TRAM, ENCO+BINI, and VEM+COBI in patients with BRAF-mutant advanced melanoma using a matching-adjusted indirect comparison (MAIC).
PATIENTS AND METHODS
A systematic literature review identified RCTs for DAB+TRAM, ENCO+BINI, and VEM+COBI in patients with BRAF-mutant advanced melanoma. Individual patient-level data for NIVO+IPI were derived from the phase III CheckMate 067 trial (BRAF-mutant cohort) and restricted to match the inclusion/exclusion criteria of the comparator trials. Treatment effects for overall survival (OS) and progression-free survival (PFS) were estimated using Cox proportional hazards and time-varying hazard ratio (HR) models. Safety outcomes (grade 3 or 4 treatment-related adverse events) with NIVO+IPI and the comparators were compared.
RESULTS
In the Cox proportional hazards analysis, NIVO+IPI showed improved OS compared with DAB+TRAM (HR = 0.53; 95% confidence interval [CI], 0.39-0.73), ENCO+BINI (HR = 0.60; CI, 0.42-0.85), and VEM+COBI (HR = 0.50; CI, 0.36-0.70) for the overall study period. In the time-varying analysis, NIVO+IPI was associated with significant improvements in OS and PFS compared with the BRAF/MEK inhibitors 12 months after treatment initiation. There were no significant differences between NIVO+IPI and BRAF/MEK inhibitor treatment from 0 to 12 months. Safety outcomes favored DAB+TRAM over NIVO+IPI, whereas NIVO+IPI was comparable to VEM+COBI.
CONCLUSION
Results of this MAIC demonstrated durable OS and PFS benefits for patients with BRAF-mutant advanced melanoma treated with NIVO+IPI compared with BRAF/MEK inhibitors, with the greatest benefits noted after 12 months.
Topics: Antineoplastic Combined Chemotherapy Protocols; Humans; Ipilimumab; Melanoma; Mitogen-Activated Protein Kinase Kinases; Nivolumab; Proto-Oncogene Proteins B-raf
PubMed: 33556898
DOI: 10.1016/j.esmoop.2021.100050 -
Medicine Jul 2022The SET-CAN/NUP214 fusion gene resulting from chromosomal del(9)(q34.11q34.13) or t(9;9) (q34;q34) has been found in T-cell acute lymphoblastic leukemia (T-ALL), B-cell...
BACKGROUND
The SET-CAN/NUP214 fusion gene resulting from chromosomal del(9)(q34.11q34.13) or t(9;9) (q34;q34) has been found in T-cell acute lymphoblastic leukemia (T-ALL), B-cell acute lymphoblastic leukemia (B-ALL), acute myeloid leukemia (AML) and myeloid sarcoma (MS). Furthermore, the SET-CAN/NUP214 fusion gene has been found in the T-ALL cell line LOUCY and the AML line MEGAL. The common features of these cases are insensitivity to chemotherapy and poor prognosis. We reviewed the characteristics and prognostic significance of the SET-CAN/NUP214 fusion gene in hematological malignancies.
METHODS
This systematic literature search was conducted using the PubMed, Web of Science, Embase, and Cochrane Library databases. With the inclusion and exclusion criteria, we summarized all of the papers and performed a statistical analyses.
RESULTS
In general, the SET-CAN/NUP214 fusion gene is very rare in adult acute leukemia, more frequently found in T-ALL than in other types of leukemia, and more often in males. Flow cytometry data indicated that the markers CD34, CD33, CD13, and CD7 were common in SET-CAN/NUP214 positive acute leukemia, including ALL. Fluorescence in situ hybridization and arrays are important methods for detecting the fusion gene in newly diagnosed patients and can detect chromosomal del(9)(q34) will be detected. The chromosomal karyotype may be normal or complex, and, in terms of survival analysis, transplantation results in a better prognosis than chemotherapy alone.
CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS
The presence of SET-CAN/NUP214 fusion gene may be a Minimal Residual Disease of early recurrence, and it might be a poor indicator of outcome.
LIMITATIONS
The mechanism, clinical characteristics, therapy and prognosis of the SET-CAN/NUP214 fusion gene in hematological malignancies require further research.
Topics: Adult; DNA-Binding Proteins; Hematologic Neoplasms; Histone Chaperones; Humans; In Situ Hybridization, Fluorescence; Leukemia, Myeloid, Acute; Male; Nuclear Pore Complex Proteins; Oncogene Proteins, Fusion; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Prognosis; Transcription Factors
PubMed: 35905214
DOI: 10.1097/MD.0000000000029294 -
Lung Cancer (Amsterdam, Netherlands) Jun 2024Crizotinib was approved to treat patients with advanced non-small cell lung cancer (aNSCLC) with ROS proto-oncogene 1 (ROS1) gene fusion in 2016. We conducted a... (Meta-Analysis)
Meta-Analysis
Efficacy and safety of crizotinib in the treatment of advanced non-small cell lung cancer with ROS1 gene fusion: a systematic literature review and meta-analysis of real-world evidence.
BACKGROUND
Crizotinib was approved to treat patients with advanced non-small cell lung cancer (aNSCLC) with ROS proto-oncogene 1 (ROS1) gene fusion in 2016. We conducted a systematic literature review to identify real-world evidence (RWE) studies and estimated the efficacy and safety of crizotinib using meta-analyses (MA) for objective response rate (ORR), real-world progression-free survival (PFS), and overall survival (OS).
METHODS
We searched MEDLINE®, Embase, and Cochrane CENTRAL from January 2016 to March 2023 using Ovid® for published single-arm or comparative RWE studies evaluating patients (N ≥ 20) receiving crizotinib monotherapy for aNSCLC with ROS1 gene fusion. Pooled estimates for ORR and grade 3/4 adverse events (AEs) were derived using the metafor package in R while pooled estimates for median real-world PFS (rwPFS) and OS were derived using reconstructed individual patient data from published Kaplan-Meier curves. The primary analysis included all studies regardless of crizotinib line of therapy; a subgroup analysis (SA) was conducted using studies evaluating patients receiving first-line crizotinib.
RESULTS
Fourteen studies met the eligibility criteria and were considered feasible for MA. For the primary analysis, the pooled ORR (N = 9 studies) was 70.6 % (95 % confidence interval [CI]: 57.0, 81.3), median rwPFS was 14.5 months (N = 11 studies), and OS was 40.2 months (N = 9 studies). In the SA, the pooled ORR (N = 4 studies) was 81.1 % (95 % CI: 76.1, 85.2) and the median rwPFS (N = 4 studies) and OS (N = 2 studies) were 18.1 and 60 months, respectively. All MAs were associated with significant heterogeneity (I > 25 %). Grade 3/4 AEs occurred in 18.7 % of patients (pooled estimate).
CONCLUSION
The results from this study are consistent with clinical trial data and, taken collectively, supports crizotinib as a safe and effective treatment across different lines of therapy in patients with ROS1 aNSCLC in the real-world setting.
Topics: Crizotinib; Humans; Carcinoma, Non-Small-Cell Lung; Lung Neoplasms; Proto-Oncogene Mas; Proto-Oncogene Proteins; Protein-Tyrosine Kinases; Protein Kinase Inhibitors; Oncogene Proteins, Fusion; Treatment Outcome; Antineoplastic Agents; Gene Fusion
PubMed: 38749072
DOI: 10.1016/j.lungcan.2024.107816 -
Medicine Feb 2020The aim of this meta-analysis was to assess the clinicopathological features and to confirm prognostic value of POLE exonuclease domain mutations (EDM) in endometrial... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The aim of this meta-analysis was to assess the clinicopathological features and to confirm prognostic value of POLE exonuclease domain mutations (EDM) in endometrial carcinoma patients.
METHODS
The PubMed, Web of Science, the data of China National Knowledge Infrastructure, and Wan fang Medical Network were systematically searched for relevant articles without a cut-off date. The keywords for the search were "endometrial cancer," "endometrial carcinoma," "EC," "POLE mutations," "POLE exonuclease domain mutations," "POLE-mutant," "clinical characteristics" "prognostic." Pooled hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by using Review manager 5.3 and Stata 14.0 statistical software.
RESULTS
Six cohort studies assessing 179 EC patients with POLE EDMs were included. The results indicated a favorable progression-free survival in POLE-mutant patients (HR = 0.32; 95% CI: = [0.09-1.18]). Furthermore, the overall survival was great in patients with POLE-mutant (HR = 0.68; 95% CI = [0.41-1.13]). It was shown that a significantly higher incidence of POLE mutations with Federation of International of Gynecologists and Obstetricians (FIGO) I group compared to FIGO II-IV group (pooled ORs: 0.34, 95% CI: [0.12-0.94], P = .04), POLE-mutant EC was not significantly associated with histology (OR = 0.56,95% CI: 0.29-1.23), tumor grade (OR = 1.22,95% CI:0.85-1.74), lymph-vascular space invasion (OR = 0.40,95% 0.06-2.42), depth of myometrial invasion (OR = 0.70,95% CI: 0.41-1.18), lymph node status (OR = 0.41, 95% 0.04-4.50), and European Society for Medical Oncology risk groups (OR = 0.68,95% CI: 0.37-1.26).
CONCLUSION
This meta-analysis has confirmed POLE EDMs may serve as a predictive biomarker of favorable prognosis. Further studies are needed to explore the appropriate clinical utility of POLE EDMs in EC.
Topics: Biomarkers, Tumor; DNA Polymerase II; Endometrial Neoplasms; Female; Humans; Lymph Nodes; Mutation; Myometrium; Neoplasm Invasiveness; Poly-ADP-Ribose Binding Proteins; Prognosis; Progression-Free Survival
PubMed: 32080141
DOI: 10.1097/MD.0000000000019281 -
Farmacia Hospitalaria : Organo Oficial... 2023Several studies quantitatively described patients with Chronic Myeloid Leukaemia on active treatment with tyrosine kinase inhibitors, however there are few qualitative... (Review)
Review
OBJECTIVE
Several studies quantitatively described patients with Chronic Myeloid Leukaemia on active treatment with tyrosine kinase inhibitors, however there are few qualitative studies that focus their results on how to accompany patients in the course of the disease over time. The objective of this review is to find out what are the expectations, information needs and experiences that determine adherence to treatment with tyrosine kinase inhibitors in patients with Chronic Myeloid Leukaemia in qualitative research articles published in the scientific literature.
METHODS
A systematic review of qualitative research articles published between 2003-2021 was carried out in PubMed/Medline, Web of Science and Embase databases. Main keywords used were: "Leukaemia, Myeloid" and "Qualitative Research". Articles on the acute phase or blast phase were excluded.
RESULTS
184 publications were located. After elimination of duplicates, 6 (3%) were included and 176 (97%) publications were excluded. Studies show that the illness is a turning point in patients' lives, and they develop their own strategies for managing the adverse effects. The factors that determine medication experiences with tyrosine kinase inhibitors should be addressed by implementing personalized strategies: this would result in early detection of problems, reinforce education at each stage and promote open discussion about complex causes underlying the treatment failure.
CONCLUSIONS
This systematic review provides evidence that implementation personalized strategies must be done to adress the factors that determine the illness experience with Chronic Myeloid Leukaemia and receiving treatment with tyrosine kinase inhibitors.
Topics: Humans; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Drug-Related Side Effects and Adverse Reactions; Fusion Proteins, bcr-abl
PubMed: 36599752
DOI: 10.1016/j.farma.2022.11.002 -
Clinical & Translational Oncology :... Aug 2019The treatment of patients with BRAFv600 mutant melanomas progressing to BRAF inhibitors (BRAFi) and immunotherapy remains challenging. Preclinical studies and a small...
BACKGROUND
The treatment of patients with BRAFv600 mutant melanomas progressing to BRAF inhibitors (BRAFi) and immunotherapy remains challenging. Preclinical studies and a small phase 2 trials have recently suggested that rechallenging with BRAFi may have a roll in these patients. The aim of this systematic review was to summarise the current evidence on the efficacy of BRAF inhibition therapy rechallenge after progression to BRAFi in metastatic BRAFv600 melanoma patients.
MATERIALS AND METHODS
We performed a systematic literature search in MEDLINE, Embase and the Cochrane Library CENTRAL up to November 2018. The target was restricted to patients with unresectable and/or metastatic BRAF V600 mutant melanoma that had previously progressed on BRAFi, were off-treatment for a period of time and then retreated with a BRAF inhibition strategy. We included prospective trials, observational studies and case reports. The primary outcomes were overall response rate (ORR), disease control rate (DCR), median progression-free survival (PFS) and median overall survival since the start of the treatment.
RESULTS
Up to November 2018, nine reports met our inclusion criteria: five case reports, three observational studies and a phase 2 trial. No comparative studies have been reported. In total, 188 patients met the inclusion criteria for this review. Efficacy results of the observational reports and the clinical trial are presented. ORR varied between 28 and 43% and DCR between 57 and 72%. Duration of response was reported in 1 retrospective study and was of 14 months. PFS varied between 4.9 and 5 months and OS was not reported in all studies.
CONCLUSION
Although no comparative studies have been conducted, rechallenging with BRAF inhibition therapy seems a plausible treatment option. Randomized trials are needed to confirm these results.
Topics: Humans; Melanoma; Molecular Targeted Therapy; Mutation; Prognosis; Protein Kinase Inhibitors; Proto-Oncogene Proteins B-raf
PubMed: 30607792
DOI: 10.1007/s12094-018-02028-0 -
European Journal of Medicinal Chemistry Nov 2020Cancer is one of the major public catastrophes worldwide and as per WHO, cancer is the leading cause of death universally after CVS disorders accounting for 9.6 million...
Cancer is one of the major public catastrophes worldwide and as per WHO, cancer is the leading cause of death universally after CVS disorders accounting for 9.6 million deaths in 2018. WHO statistics revealed five dangerous types of cancer viz. lung, breast, colorectal, prostate and skin. In male, lung cancer causes highest death, while in female, breast cancer causes the most. Alteration in MAPK signalling pathway plays a significant role in majority of cancer cases. Raf protein is activated by phosphorylation via downstream regulation of the MAPK pathway. Raf composed of 3 subtypes, viz. A-Raf, B-Raf, and C-Raf. B-Raf kinase plays a significant role in healthy cell growth in the MAPK pathway and the problem associated with B-Raf mutation leads to the development of cancer and other diseases. The progression of mutant B-Raf (B-Raf) protein is higher in cancer as compare to other diseases. In 2002, B-Raf mutation was identified for the first time in the development of cancer. The frequency of B-Raf mutation is higher in melanoma, thyroid, colorectal and ovarian cancer. We have covered small molecule B-Raf inhibitors reported in various literatures; from 2002 to 2020 and also covered clinical trial data. To widen the scope of readers, we compiled details of small molecules, specifically inhibiting B-Raf mutant and showing anti-proliferative activity against various cancer cell lines along with in-vivo data. We believe that the information covered here will be important in signifying the potentials of B-Raf mutation and its inhibitors as potent anticancer agents.
Topics: Animals; Antineoplastic Agents; Humans; Molecular Targeted Therapy; Mutation; Neoplasms; Proto-Oncogene Proteins B-raf
PubMed: 32798788
DOI: 10.1016/j.ejmech.2020.112675 -
Farmacia Hospitalaria : Organo Oficial... 2023Several studies quantitatively described patients with Chronic Myeloid Leukemia on active treatment with tyrosine kinase inhibitors, however there are few qualitative... (Review)
Review
OBJECTIVE
Several studies quantitatively described patients with Chronic Myeloid Leukemia on active treatment with tyrosine kinase inhibitors, however there are few qualitative studies that focus their results on how to accompany patients in the course of the disease over time. The objective of this review is to find out what are the expectations, information needs and experiences that determine adherence to treatment with tyrosine kinase inhibitors in patients with Chronic Myeloid Leukemia in qualitative research articles published in the scientific literature.
METHODS
A systematic review of qualitative research articles published between 2003-2021 was carried out in PubMed/Medline, Web of Science and Embase databases. Main keywords used were: "Leukemia, Myeloid" and "Qualitative Research". Articles on the acute phase or blast phase were excluded.
RESULTS
184 publications were located. After elimination of duplicates, 6 (3%) were included and 176 (97%) publications were excluded. Studies show that the illness is a turning point in patients' lives, and they develop their own strategies for managing the adverse effects. The factors that determine medication experiences with tyrosine kinase inhibitors should be addressed by implementing personalized strategies: this would result in early detection of problems, reinforce education at each stage and promote open discussion about complex causes underlying the treatment failure.
CONCLUSIONS
This systematic review provides evidence that implementation personalized strategies must be done to adress the factors that determine the illness experience with Chronic Myeloid Leukemia and receiving treatment with tyrosine kinase inhibitors.
Topics: Humans; Antineoplastic Agents; Tyrosine Kinase Inhibitors; Protein Kinase Inhibitors; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Drug-Related Side Effects and Adverse Reactions; Fusion Proteins, bcr-abl
PubMed: 36870818
DOI: 10.1016/j.farma.2023.02.002 -
Annals of Hematology Dec 2019U2 small nuclear RNA auxiliary factor 1 (U2AF1) mutant is the most common molecular biological abnormality in patients with myelodysplastic syndromes. Some studies have... (Meta-Analysis)
Meta-Analysis
U2 small nuclear RNA auxiliary factor 1 (U2AF1) mutant is the most common molecular biological abnormality in patients with myelodysplastic syndromes. Some studies have reported the prognostic impact of U2AF1 mutant in patients with de novo MDS, with discrepant results, so we do a meta-analysis about the relevant literatures to further investigate their prognostic impact on patients with de novo MDS. We conducted a literature search on databases such as PubMed, Embase, and the Cochrane Library to obtain studies on the prognosis of U2AF1 mutant in patients with de novo MDS published up to August 9, 2018. The primary endpoint was overall survival (OS), and the secondary endpoint was acute myeloid leukemia (AML) transformation. We extracted the hazard ratios (HRs) of OS and AML transformation and their 95% confidence intervals (CIs). Meta-analysis was performed by selecting a fixed-effect model or a random-effects model based on the heterogeneity between studies. A total of 14 cohort studies were included in the final meta-analysis, including 3322 patients with de no MDS, in which 390 patients were associated with U2AF1 mutant. The results showed that U2AF1 mutant had an adverse prognostic impact on OS (HR = 1.84, 95% CI: 1.45-2.33, P < 0.00001) and AML transformation (HR = 2.47, 95% CI: 1.50-4.06, P = 0.0004). U2AF1 mutant was associated with shorter OS in subgroup analyses of low- or intermediate-1-IPSS, U2AF1 and U2AF1. Out meta-analysis indicates that U2AF1 mutants are independent, detrimental prognostic factors for OS and AML transformation in patients with de novo MDS, as well as associating with shorter OS in subgroups of low- or intermediate-1-IPSS, U2AF1 and U2AF1. Further prospective studies are needed in the future, and subgroup analysis of U2AF1 subgroups is needed to obtain a more reliable basis for the impact of U2AF1 mutant on the prognosis of de novo MDS.
Topics: Disease-Free Survival; Female; Humans; Leukemia, Myeloid, Acute; Male; Models, Biological; Mutation; Myelodysplastic Syndromes; Neoplasm Proteins; Splicing Factor U2AF; Survival Rate
PubMed: 31754743
DOI: 10.1007/s00277-019-03843-3