-
Future Oncology (London, England) Jan 2022Recent studies showed that -fusion variants are associated with heterogeneous clinical outcomes. However, contradictory conclusions have been drawn in other studies... (Meta-Analysis)
Meta-Analysis
Recent studies showed that -fusion variants are associated with heterogeneous clinical outcomes. However, contradictory conclusions have been drawn in other studies showing no correlation between variants and prognoses. A systematic review and meta-analysis was performed to evaluate the prognostic value of fusion variants for patient outcomes. 28 studies were included in the analysis. According to the pooled results, patients harboring variant 1 showed equivalent progression-free survival (PFS) and overall survival (OS) with non-v1 patients (hazard ratio [HR] for PFS: 0.91 [0.68-1.21]; p = 0.499; OS: 1.12 [0.73-1.72]; p = 0.610). Similarly, patients with v3 showed the same disease progress as non-v3 patients (pooled HR for PFS = 1.07 [0.72-1.58]; p = 0.741). However, pooled results for OS suggested that patients with v3 had worse survival than non-v3 patients (HR = 3.44 [1.42-8.35]; p = 0.006). Results suggest that patients with v1 exhibited no significant difference from non-v1 in terms of OS and PFS, while v3 was associated with shorter OS in -positive patients with non-small cell lung cancer.
Topics: Biomarkers, Tumor; Carcinoma, Non-Small-Cell Lung; Genetic Variation; Humans; Lung Neoplasms; Oncogene Proteins, Fusion; Prognosis; Progression-Free Survival; Risk Assessment
PubMed: 34783600
DOI: 10.2217/fon-2021-0945 -
The Oncologist Aug 2022This review summarizes the case studies of PCM1-JAK2 fusion tyrosine kinase gene-related neoplasia. Recommended treatment includes JAK2 inhibitors and hematologic stem...
BACKGROUND
This review summarizes the case studies of PCM1-JAK2 fusion tyrosine kinase gene-related neoplasia. Recommended treatment includes JAK2 inhibitors and hematologic stem cell transplantation (HSCT), although the small number of patients has limited study of their efficacy. Herein, we present all available cases in the current searchable literature with their demographics, diagnoses, treatments, and outcomes.
METHODS
PubMed, ScienceDirect, Publons, the Cochrane Library, and Google were searched with the following terms: PCM1-JAK2, ruxolitinib and myeloid/lymphoid.
RESULTS
Sixty-six patients (mean age = 50, 77% male) had an initial diagnosis of myeloproliferative neoplasm (MPN) in 40, acute leukemia in 21 and T-cell cutaneous lymphoma in 5. Thirty-five patients (53%) had completed 5-year follow-up. The 5-year survival for the MPN, acute myelogenous leukemia (AML), acute lymphocytic leukemia, and lymphoma groups are 62.7, 14.9%, 40.0%, and 100%, respectively. Too few patients have been treated with ruxolitinib to draw conclusions regarding its effect on survival while the 5-year survival for MPN patients with or without HSCT was 80.2% (40.3%-94.8%) versus 51.5% (22.3%-74.6%), respectively. The T-cell cutaneous lymphoma patients have all survived at least 7 years.
CONCLUSION
This rare condition may be increasingly detected with wider use of genomics. Ruxolitinib can yield hematologic and molecular remissions. However, HSCT is, at this time, the only potentially curative treatment. Useful prognostic markers are needed to determine appropriate timing for HSCT in patients with MPN. Patients presenting with acute leukemia have a poor prognosis.
Topics: Female; Humans; Janus Kinase 2; Leukemia; Lymphoma; Male; Middle Aged; Myeloproliferative Disorders; Oncogene Proteins, Fusion
PubMed: 35472244
DOI: 10.1093/oncolo/oyac072 -
European Journal of Cancer (Oxford,... Nov 2021Activating genomic alterations of the receptor tyrosine kinase KIT are found preferentially in certain melanoma subtypes such as acral and mucosal melanoma or melanoma... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Activating genomic alterations of the receptor tyrosine kinase KIT are found preferentially in certain melanoma subtypes such as acral and mucosal melanoma or melanoma arising in chronically sun-damaged skin. However, the therapeutic value of c-Kit inhibitors for these subtypes currently remains unclear.
OBJECTIVES
The objective of this study was to summarise the efficacy and safety of c-Kit inhibitors for unresectable or metastatic mucosal, acral or chronically sun-damaged melanoma.
METHODS
We performed a systematic literature research in MEDLINE, Embase and CENTRAL and hand searched pertinent trial registers and conference abstracts for eligible trials until 23rd June 2020. Results were pooled using a random-effects model to calculate pooled proportions of objective response rates (ORRs) and severe adverse events (sAEs) from unselected KIT mutant or amplified cohorts.
RESULTS
Nineteen single-arm studies with an overall sample size of 601 patients were included. The studies investigated imatinib (n = 8), nilotinib (n = 7), dasatinib (n = 3) and sunitinib (n = 1). The pooled ORR for all inhibitors was 15% (95% confidence interval [CI]: 12-18%). Subgroup analysis revealed the highest ORR (20%; 95% CI: 14-26%) for nilotinib. The ORR for mucosal melanoma was 14% (95% CI: 6-24%) and 22% for acral lentiginous melanoma (95% CI: 14-30%). At least one sAE was reported in 42% of patients (95% CI: 34-50%).
CONCLUSIONS
c-Kit inhibitors represent a valuable treatment option for patients with KIT-mutant melanoma, in particular for mutations of exons 11 and 13. Furthermore, high-quality trials are urgently needed to investigate putative combinations of specific targeted therapies with immunotherapy.
Topics: Dasatinib; Exons; Humans; Imatinib Mesylate; Melanoma; Mucous Membrane; Mutation; Progression-Free Survival; Protein Kinase Inhibitors; Proto-Oncogene Proteins c-kit; Pyrimidines; Skin; Skin Neoplasms; Sunitinib; Sunlight
PubMed: 34562816
DOI: 10.1016/j.ejca.2021.08.015 -
Leukemia Research Feb 2021Chronic Myeloid Leukemia (CML) is characterized by the overproduction of BCR-ABL, a tyrosine kinase with constitutive activity, in which the majority of CML patients... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic Myeloid Leukemia (CML) is characterized by the overproduction of BCR-ABL, a tyrosine kinase with constitutive activity, in which the majority of CML patients have e13a2 or e14a2 transcripts. Reckoned the possible associations between the hematologic and molecular features of the disease, a profound understanding of different aspects of this neoplasm would be provided.
METHOD
The authors implemented a systematic literature search, utilizing the terms published articles or internationally accepted abstracts from PubMed, Embase, Medline, Cochrane library before January 2019. Weighted mean proportion and 95 % confidence intervals (CIs) of CML prevalence calculated using a fixed-effects and a random-effects model. Statistical heterogeneity was evaluated using the I2 statistic.
RESULTS
34 studies for a total of 54,034 Patients were selected and included in the review. Results revealed that compared to e13a2 group, the overall estimated prevalence is much higher in the e14a2 (39 % and 54 %, respectively). Besides, the overall estimated prevalence ratio of male to female was higher in the e13a2 group in comparison to e14a2 (1.08 and 0.856 respectively). The overall estimated prevalence of dual transcription of e13a2/e14a2 was 1.11 %, and male/female overall estimated prevalence ratio was 1.18.
CONCLUSION
This meta-analysis of CML patients demonstrated the e14a2 as the more common transcript type. Usually, the e14a2 transcript is prevalent in females, whereas e13a2 and dual transcription of e13a2/e14a2 are more common in men. These data explicate that the differences in proportion are not by chance. This is crucial, as the transcript type is a variable suspected to be of prognostic importance for the treatment-related response, the outcome of treatment, and the rate of treatment-free remission.
Topics: Female; Fusion Proteins, bcr-abl; Humans; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Male; Prevalence; Prognosis; Sex Characteristics
PubMed: 33524640
DOI: 10.1016/j.leukres.2021.106512 -
Journal of Neurology Aug 2022This study aims to determine the genetic and clinical features of TARDBP-mutated patients in our cohort of Chinese patients with amyotrophic lateral sclerosis (ALS)...
Genotype-phenotype association of TARDBP mutations in Chinese patients with amyotrophic lateral sclerosis: a single-center study and systematic review of published literature.
BACKGROUND
This study aims to determine the genetic and clinical features of TARDBP-mutated patients in our cohort of Chinese patients with amyotrophic lateral sclerosis (ALS) combined with data in the literature.
METHODS
We performed TARDBP mutation screening in 1258 Chinese ALS patients, including 1204 sporadic ALS (sALS) and 54 familial ALS (fALS) patients. A systematic literature review was conducted by searching TARDBP-mutated patients from China in the online databases.
RESULTS
In our cohort, the mutant frequency of TARDBP variants was 0.3% (4/1258), with two recurrent variants (p.G294V, p.G298V) and one novel variant (p.S332G) identified. Combining with data in the literature review, the TARDBP-mutant frequency in the Chinese population was 1.4% (83/5998), with 0.8% (46/5470) in sALS and 7.0% (37/528) in fALS. Most patients had limb onset (63.0%), with an average life expectancy of 4.3 years (range 0.5-13). Disease durations significantly differed (p = 0.002), with p.M337V showing the longest duration (80 months) and p.N378D showing the shortest duration (16.7 months).
CONCLUSION
Our study found that TARDBP mutation was not rare in Chinese fALS patients. Different TARDBP mutations were associated with specific features in phenotypes.
Topics: Amyotrophic Lateral Sclerosis; Asian People; DNA-Binding Proteins; Genetic Association Studies; Humans; Mutation
PubMed: 35239007
DOI: 10.1007/s00415-022-11042-w -
Frontiers in Oncology 2024Immunotherapy, frequently combined with conventional chemotherapy, is crucial for treating NSCLC. Kirsten rat sarcoma virus (KRAS) is a poor prognostic factor in...
BACKGROUND
Immunotherapy, frequently combined with conventional chemotherapy, is crucial for treating NSCLC. Kirsten rat sarcoma virus (KRAS) is a poor prognostic factor in patients with NSCLC, particularly lung adenocarcinoma, where binding of conventional inhibitors to mutated KRAS proteins is challenging. Field profiles, research hotspots, and prospects for immunotherapy for patients with NSCLC-carrying KRAS mutations were uncovered in this study.
METHODS
Microsoft Excel 2019, Bibliometrix, VOSviewer software, and Citespace were utilized to conduct a comprehensive scientometric analysis and understand a specific research field's knowledge base and frontiers aided by bibliometrics.
RESULTS
Between 2014 and 2023, 398 eligible documents in the English language were acquired using the WoSCC database, of which 113 and 285 were reviews and articles, respectively. The growth rate per year was 34.25 %. The most cited articles were from the United States, and China published the highest number of articles. Cancers was the journal, with increased publications in recent years. The keywords with the strongest citation bursts were analyzed using Citespace. "Immune checkpoint inhibitors," "co-occurring genomic alterations," and "KRAS" are among the research hotspots in this field.
CONCLUSION
Using bibliometric and visual analyses, we examined immunotherapy for patients with KRAS-mutant NSCLC over the previous decade. The whole analysis showed a steady, quick increase in yearly publications in this area. Our findings will provide a roadmap for future research on the mechanisms of immunotherapy and immune checkpoint inhibitor action in treating KRAS-mutant NSCLC.
PubMed: 38817907
DOI: 10.3389/fonc.2024.1385761 -
Oncology Reports Mar 2020Gastrointestinal stromal tumors (GISTs) are the most commonly observed mesenchymal tumors of the digestive tract, and they originate from the interstitial cells of...
Gastrointestinal stromal tumors (GISTs) are the most commonly observed mesenchymal tumors of the digestive tract, and they originate from the interstitial cells of Cajal. GISTs can be divided into KIT/PDGFRA‑mutant GISTs and wild‑type GISTs based on the presence or absence of KIT/PDGFRA mutations. Wild‑type GISTs can be divided into succinate dehydrogenase complex (SDH)‑deficient GISTs and non‑SDH‑deficient GISTs. Downstream signaling pathways activated by these mutations serve a pivotal role in the development of GISTs and are associated with the biological behavior, including risk stratification, clinical prognosis and drug resistance. Accurate medical care requires accurate molecular diagnosis, which in turn prolongs the survival of patients with GISTs and makes GIST a chronic disease. At present, there is a lack of effective treatment for imatinib/sunitinib/regorafenib resistant patients and KIT/PDGFRA‑WT GISTs, which is undoubtedly a major challenge for future research. The present review summarizes the molecular pathogenesis of GISTs and the progress of related research.
Topics: Drug Resistance, Neoplasm; Gastrointestinal Stromal Tumors; Genetic Heterogeneity; Humans; Imatinib Mesylate; Phenylurea Compounds; Prognosis; Proto-Oncogene Proteins c-kit; Pyridines; Receptor, Platelet-Derived Growth Factor alpha; Succinate Dehydrogenase; Sunitinib
PubMed: 32020209
DOI: 10.3892/or.2020.7470 -
Mycoses Oct 2019Phaeohyphomycosis is a chronic cutaneous, subcutaneous or systemic mycotic infection caused by various dematiaceous fungi. The diverse clinical manifestations and poor...
BACKGROUND
Phaeohyphomycosis is a chronic cutaneous, subcutaneous or systemic mycotic infection caused by various dematiaceous fungi. The diverse clinical manifestations and poor prognosis of phaeohyphomycosis necessitate studies on it to better recognise the disease and improve its management.
OBJECTIVES
To investigate the epidemiology, aetiology, diagnosis, treatment and prognosis of phaeohyphomycosis in China over the past 20 years, and to study the first case of phaeohyphomycosis caused by Phialophora americana and the genetic and immunological mechanisms.
PATIENTS/METHODS
Clinical and laboratory findings of the case were studied, and the patient's DNA was sequenced for CARD9, followed by immunological studies using patient's PBMCs. Cases of phaeohyphomycosis in China from 1998 to 2018 in both the Chinese and English literature were collected and analysed, including 45 articles and 46 patients.
RESULTS
We confirmed the patient holding a homozygous frameshift mutation of CARD9, which led to impairment of pro-inflammatory cytokine production, and lower Th17- and Th22-associated responses upon fungus-specific stimulation. From the literature review, we revealed that the clinical presentations of phaeohyphomycosis were diverse. Diagnoses were established mainly on the basis of histopathology and fungal culture. Oral itraconazole, voriconazole, and posaconazole are the first choices for treatment, and a combination with surgical excision is also recommended.
CONCLUSIONS
Our study establishes that obtaining detailed histories is vital for understanding the immune state and that patients with recurrent or chronic phaeohyphomycosis in the absence of known immunodeficiencies should be tested for CARD9 mutations. We hope our findings will aid clinicians in the diagnoses and treatment of such infections.
Topics: Adolescent; Adult; Aged; Antifungal Agents; CARD Signaling Adaptor Proteins; Child; Child, Preschool; China; Cytokines; Female; Frameshift Mutation; Humans; Male; Middle Aged; Mutant Proteins; Phaeohyphomycosis; Phialophora; Sequence Analysis, DNA; T-Lymphocytes; Young Adult
PubMed: 31271673
DOI: 10.1111/myc.12962 -
Neurosurgical Focus Dec 2019With the revised WHO 2016 classification of brain tumors, there has been increasing interest in imaging biomarkers to predict molecular status and improve the yield of...
The T2-FLAIR-mismatch sign as an imaging biomarker for IDH and 1p/19q status in diffuse low-grade gliomas: a systematic review with a Bayesian approach to evaluation of diagnostic test performance.
OBJECTIVE
With the revised WHO 2016 classification of brain tumors, there has been increasing interest in imaging biomarkers to predict molecular status and improve the yield of genetic testing for diffuse low-grade gliomas (LGGs). The T2-FLAIR-mismatch sign has been suggested to be a highly specific radiographic marker of isocitrate dehydrogenase (IDH) gene mutation and 1p/19q codeletion status in diffuse LGGs. The presence of T2-FLAIR mismatch indicates a T2-hyperintense lesion that is hypointense on FLAIR with the exception of a hyperintense rim.
METHODS
In accordance with PRISMA guidelines, we performed a systematic review of the Ovid Medline, Embase, Scopus, and Cochrane databases for reports of studies evaluating the diagnostic performance of T2-FLAIR mismatch in predicting the IDH and 1p/19q codeletion status in diffuse LGGs. Results were combined into a 2 × 2 format, and the following diagnostic performance parameters were calculated: sensitivity, specificity, positive predictive value, negative predictive value, and positive (LR+) and negative (LR-) likelihood ratios. In addition, we utilized Bayes theorem to calculate posttest probabilities as a function of known pretest probabilities from previous genome-wide association studies and the calculated LRs. Calculations were performed for 1) IDH mutation with 1p/19q codeletion (IDHmut-Codel), 2) IDH mutation without 1p/19q codeletion (IDHmut-Noncodel), 3) IDH mutation overall, and 4) 1p/19q codeletion overall. The QUADAS-2 (revised Quality Assessment of Diagnostic Accuracy Studies) tool was utilized for critical appraisal of included studies.
RESULTS
A total of 4 studies were included, with inclusion of 2 separate cohorts from a study reporting testing and validation (n = 746). From pooled analysis of all cohorts, the following values were obtained for each molecular profile-IDHmut-Codel: sensitivity 30%, specificity 73%, LR+ 1.1, LR- 1.0; IDHmut-Noncodel: sensitivity 33.7%, specificity 98.5%, LR+ 22.5, LR- 0.7; IDH: sensitivity 32%, specificity 100%, LR+ 32.1, LR- 0.7; 1p/19q codeletion: sensitivity 0%, specificity 54%, LR+ 0.01, LR- 1.9. Bayes theorem was used to calculate the following posttest probabilities after a positive and negative result, respectively-IDHmut-Codel: 32.2% and 29.4%; IDHmut-Noncodel: 95% and 40%; IDH: 99.2% and 73.5%; 1p/19q codeletion: 0.4% and 35.1%.
CONCLUSIONS
The T2-FLAIR-mismatch sign is an insensitive but highly specific marker of IDH mutation but not 1p/19q codeletion in diffuse LGGs, although there may be significant exceptions. These findings support the utility of T2-FLAIR mismatch as an imaging-based biomarker for positive selection of patients with IDH-mutant gliomas.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Brain Neoplasms; Chromosomes, Human, Pair 1; DNA Mutational Analysis; Female; Gene Deletion; Glioma; Humans; Isocitrate Dehydrogenase; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Proteins; Neuroimaging; Predictive Value of Tests; Sensitivity and Specificity; Young Adult
PubMed: 31786548
DOI: 10.3171/2019.9.FOCUS19660 -
Acta Oncologica (Stockholm, Sweden) Jul 2020The analysis of the BRAF mutational status has been established as a standard procedure during diagnosis of advanced malignant melanoma due to the fact that BRAF... (Meta-Analysis)
Meta-Analysis
The analysis of the BRAF mutational status has been established as a standard procedure during diagnosis of advanced malignant melanoma due to the fact that BRAF inhibitors constitute a cornerstone in the treatment of metastatic disease. However, the general impact of BRAF mutational status on survival remains unclear. Our study aimed to assess the underlying prognostic significance of BRAF mutant versus wild type (WT) malignant melanoma on overall survival (OS), disease-free survival (DFS) and progression-free survival (PFS). A systematic literature search in EMBASE, Medline and Cochrane CENTRAL was performed. Studies were included if they reported survival outcomes for BRAF mutant versus WT patients as hazard ratios (HR) or in Kaplan-Meier (KM) curves. Random-effects meta-analysis models were used to pool HRs across the studies. Data from 52 studies, representing 7519 patients, were pooled for analysis of OS. The presence of a BRAF mutation was statistically significantly associated with a reduced OS (HR [95% confidence interval (CI)]: 1.23 [1.09-1.38]), however, with substantial heterogeneity between the studies (: 58.0%). Meta-regression and sensitivity analyses showed that age, sex and BRAF mutation testing method did not have a significant effect on the OS HR. BRAF mutant melanoma showed comparable effect on DFS to non-BRAF mutant melanoma in stage I-III melanoma (combined HR: 1.16, 95% CI: 0.92-1.46), and on PFS in stage III-IV (HR: 0.98 (95% CI: 0.68-1.40)). Although there was substantial heterogeneity between the studies, the overall results demonstrated a poorer prognosis and OS in patients harbouring BRAF mutations. Future studies should take this into account when evaluating epidemiological data and treatment effects of new interventions in patients with malignant melanoma.
Topics: Disease-Free Survival; Humans; Melanoma; Mutation; Neoplasm Staging; Progression-Free Survival; Proto-Oncogene Proteins B-raf; Skin Neoplasms; Survival Rate
PubMed: 32285732
DOI: 10.1080/0284186X.2020.1747636