Reliability of BRAF mutation detection using plasma sample: A protocol for systematic review and meta-analysis: Erratum

3557 Background: Mismatch repair deficient/microsatellite instability high (dMMR/MSI-H) colorectal cancer (CRC) defines a molecular subtype with distinct clinicopathologic characteristics including an excellent response to immunotherapy. Although BRAF mutations are established as a negative prognostic marker in CRC, whether they retain their negative prognostic impact in or alter the response to immunotherapy in dMMR/MSI-H CRC remains unknown. Herein, we present a systematic review and meta-analysis of the impact of BRAF mutations on the overall survival (OS) and immune checkpoint inhibitor (ICI) response in dMMR/MSI-H CRC. Methods: Studies published from inception to 26 January 2021 were searched in PubMed, Embase, and major conference proceedings (AACR, ASCO, and ESMO). Eligible studies included the following: 1) observational studies reporting outcomes based on BRAF mutation status in dMMR/MSI-H CRC patients and 2) experimental studies of ICI reporting outcomes based on BRAF mutation status in dMMR/MSI-H CRC patients. A summary hazard ratio (HR) was calculated for OS in BRAF mutated ( BRAFmut) vs. BRAF wild type ( BRAFwt) patients (pts) with the random effects meta-analysis (REM). A summary odds ratio (OR) was calculated for objective response rate (ORR) in BRAFmut vs. BRAFwt pts treated with ICI with the REM. Results: Database search conducted according to PRISMA guidelines found 4221 studies in total. Initial screening identified 30 studies and after full-text review, 9 studies (N = 4158 pts) were included for the meta-analysis of prognosis (analysis A) and 3 studies (N = 178 pts) were included for the meta-analysis of ICI response (analysis B). The outcome measures are summarized in the table below. Analysis A showed that in stage I-IV dMMR/MSI-H CRC pts, BRAFmut was associated with worse OS than BRAFwt (HR 1.57, 1.23-1.99). The heterogeneity was low (I2 = 21%). Subgroup analysis showed no significant difference in the prognostic impact of BRAF mutation status between stage IV only and stage I-IV CRC pts. Analysis B showed no difference in ORR (OR 1.04, 0.48-2.25) between BRAFmut vs. BRAFwt dMMR/MSI-H pts who received ICI. The heterogeneity was low (I2 = 0%). Conclusions: BRAF mutations retain their negative prognostic impact in dMMR/MSI-H stage I-IV and stage IV CRC but are not associated with differential ICI response. Limitations include the following: analysis A was based on retrospective studies; also, the impact of BRAF status on the survival outcome of ICI could not be assessed due to limited number of studies.[Table: see text]

Download Full-text

Clinical impact of BRAF mutation on the diagnosis and prognosis of papillary thyroid carcinoma: a systematic review and meta-analysis

European Journal of Clinical Investigation ◽

10.1111/eci.12577 ◽

2016 ◽

Vol 46 (2) ◽

pp. 146-157 ◽

Cited By ~ 18

Author(s):

Zhen Wang ◽

Jun-Qiang Chen ◽

Jin-Lu Liu ◽

Xin-Gan Qin

Keyword(s):

Systematic Review ◽

Papillary Thyroid Carcinoma ◽

Thyroid Carcinoma ◽

Braf Mutation ◽

Meta Analysis ◽

Clinical Impact ◽

Papillary Thyroid ◽

Diagnosis And Prognosis

Download Full-text

BRAF Mutation is Associated with an Improved Survival in Glioma—a Systematic Review and Meta-analysis

Molecular Neurobiology ◽

10.1007/s12035-017-0599-y ◽

2017 ◽

Cited By ~ 8

Author(s):

Huy Gia Vuong ◽

Ahmed M. A. Altibi ◽

Uyen N. P. Duong ◽

Hanh T. T. Ngo ◽

Thong Quang Pham ◽

...

Keyword(s):

Systematic Review ◽

Braf Mutation ◽

Meta Analysis

Download Full-text

The Prognostic Value of BRAF Mutation in Colorectal Cancer and Melanoma: A Systematic Review and Meta-Analysis

PLoS ONE ◽

10.1371/journal.pone.0047054 ◽

2012 ◽

Vol 7 (10) ◽

pp. e47054 ◽

Cited By ~ 124

Author(s):

Gholamreza Safaee Ardekani ◽

Seyed Mehdi Jafarnejad ◽

Larry Tan ◽

Ardavan Saeedi ◽

Gang Li

Keyword(s):

Colorectal Cancer ◽

Systematic Review ◽

Braf Mutation ◽

Prognostic Value ◽

Meta Analysis

Download Full-text

BRAF mutation as a prognostic marker for survival in malignant melanoma: A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2018.36.15_suppl.e21566 ◽

2018 ◽

Vol 36 (15_suppl) ◽

pp. e21566-e21566 ◽

Cited By ~ 5

Author(s):

Lars Ny ◽

Marta Nyakas ◽

Micaela Hernberg ◽

Jussi Koivunen ◽

Lars Oddershede ◽

...

Keyword(s):

Systematic Review ◽

Malignant Melanoma ◽

Prognostic Marker ◽

Braf Mutation ◽

Meta Analysis

Download Full-text

Adjuvant Therapy of High-Risk (Stages IIC–IV) Malignant Melanoma in the Post Interferon-Alpha Era: A Systematic Review and Meta-Analysis

Frontiers in Oncology ◽

10.3389/fonc.2020.637161 ◽

2021 ◽

Vol 10 ◽

Author(s):

Konstantinos Christofyllakis ◽

Claudia Pföhler ◽

Moritz Bewarder ◽

Cornelia S. L. Müller ◽

Lorenz Thurner ◽

...

Keyword(s):

Systematic Review ◽

High Risk ◽

Malignant Melanoma ◽

Adjuvant Therapy ◽

Adjuvant Treatment ◽

Braf Mutation ◽

Meta Analysis ◽

Stage Iiia ◽

Free Survival ◽

Braf Mutant

IntroductionMultiple agents are approved in the adjuvant setting of completely resected high-risk (stages IIC–IV) malignant melanoma. Subgroups may benefit differently depending on the agent used. We performed a systematic review and meta-analysis to evaluate the efficiency and tolerability of available options in the post interferon era across following subgroups: patient age, stage, ulceration status, lymph node involvement, BRAF status.MethodsThe PubMed and Cochrane Library databases were searched without restriction in year of publication in June and September 2020. Data were extracted according to the PRISMA Guidelines from two authors independently and were pooled according to the random-effects model. The predefined primary outcome was recurrence-free survival (RFS). Post-data extraction it was noted that one trial (BRIM8) reported disease-free survival which was defined in the exact same way as RFS.ResultsFive prospective randomized placebo-controlled trials were included in the meta-analysis. The drug regimens included ipilimumab, pembrolizumab, nivolumab, nivolumab/ipilimumab, vemurafenib, and dabrafenib/trametinib. Adjuvant treatment was associated with a higher RFS than placebo (HR 0.57; 95% CI= 0.45–0.71). Nivolumab/ipilimumab in stage IV malignant melanoma was associated with the highest RFS benefit (HR 0.23; 97.5% CI= 0.12–0.45), followed by dabrafenib/trametinib in stage III BRAF-mutant melanoma (HR 0.49; 95% CI= 0.40–0.59). The presence of a BRAF mutation was associated with higher RFS rates (HR 0.30; 95% CI= 0.11–0.78) compared to the wildtype group (HR 0.60; 95% CI= 0.44–0.81). Patient age did not influence outcomes (≥65: HR 0.50; 95% CI= 0.36–0.70, <65: HR 0.58; 95% CI= 0.46–0.75). Immune checkpoint inhibitor monotherapy was associated with lower RFS in non-ulcerated melanoma. Patients with stage IIIA benefited equally from adjuvant treatment as those with stage IIIB/C. Nivolumab/ipilimumab and ipilimumab monotherapy were associated with higher toxicity.ConclusionAdjuvant therapy should not be withheld on account of advanced age or stage IIIA alone. The presence of a BRAF mutation is prognostically favorable in terms of RFS. BRAF/MEK inhibitors should be preferred in the adjuvant treatment of BRAF-mutant non-ulcerated melanoma.

Download Full-text