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Efficacy of D5F3 IHC for detecting ALK gene rearrangement in NSCLC patients: a systematic review and meta-analysis.

ABSTRACT: We conducted a pooled analysis comparing the efficacy of an immunohistochemistry (IHC) assay using the D5F3 antibody with that of fluorescence in situ hybridization (FISH) for detecting ALK gene rearrangement in NSCLC patients. A total of 32 studies involving 5805 samples were included in this review. Pooled sensitivity for D5F3 IHC was 0.97 (95%CI: 0.93-0.98), specificity was 0.99 (95%CI: 0.98-1.00), PLR was 119.20 (95%CI: 57.79-245.89), NLR was 0.03 (95%CI: 0.02-0.07), DOR was 3526.66 (95%CI: 1344.71-9249.03), and AUROC was 1.00 (95%CI: 0.99-1.00). Meta-regression revealed that specimen type was a source of heterogeneity for specificity, and specimen type and FISH signal distance were sources of heterogeneity in the joint model. Subgroup analysis revealed that sensitivity and specificity were higher when the FISH signal distance standard was ? 2 than when it was ? 1. Sensitivity was higher for tumor specimens than for cell specimens; specificity was higher for cell specimens than for tumor specimens. In conclusion, the D5F3 IHC assay was nearly as effective as FISH for detection of ALK gene rearrangement in NSCLC patients.

SUBMITTER: Ma H

PROVIDER: S-EPMC5342540 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Efficacy of D5F3 IHC for detecting ALK gene rearrangement in NSCLC patients: a systematic review and meta-analysis.

Ma Hu H Yao Wen-Xiu WX Huang Lang L Jin Su-Han SH Liu Da-Hai DH Liu Yuan Y Tian Xu X Tian Jin-Hui JH Zhou Jian-Guo JG

Oncotarget 20161001 43

We conducted a pooled analysis comparing the efficacy of an immunohistochemistry (IHC) assay using the D5F3 antibody with that of fluorescence in situ hybridization (FISH) for detecting ALK gene rearrangement in NSCLC patients. A total of 32 studies involving 5805 samples were included in this review. Pooled sensitivity for D5F3 IHC was 0.97 (95%CI: 0.93-0.98), specificity was 0.99 (95%CI: 0.98-1.00), PLR was 119.20 (95%CI: 57.79-245.89), NLR was 0.03 (95%CI: 0.02-0.07), DOR was 3526.66 (95%CI: ...[more]

PMID: 27602773

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Project description:IntroductionRadiotherapy (RT) is currently the main treatment for brain metastases (BMs) from non-small cell lung cancer (NSCLC). Due to the short survival time and obvious adverse reactions of RT, we urgently need more appropriate treatment. This network meta-analysis reviewed the efficacy and adverse effects of radiotherapy-based combination therapy for patients without targeted epidermal growth factor receptor (EGFR) mutations/anaplastic lymphoma kinase (ALK) gene rearrangement NSCLC BMs, to screen out the therapy with the best efficacy.MethodsPubMed, Embase, Web of Science, and Cochrane Library were searched from the earliest publication date available to 1 April 2022. STATA15.0 was used to conduct heterogeneity analysis, sensitivity analysis, forest plot analysis, and publication bias analysis.ResultsA total of 28 studies, involving 3707 patients were included in the Bayesian network meta-analysis. In the limited paired meta-analysis for head-to-head comparative trials, compared with RT-based combination therapy, RT combined with Immune checkpoint inhibitors (ICIs) showed significant overall survival (OS) benefit (HR 0.65, 95%CI 0.47-0.9, p<0.01), RT combined with ICIs showed a non-significant difference for intracranial progression-free survival (iPFS) (HR 0.76, 95%CI 0.27-2.27, p<0.01) and progression-free survival (PFS) (HR 0.9, 95%CI 0.36-2.37, p<0.01). In addition, according to the ranking results, compared with RT combined with chemotherapy(CT) or with targeted therapy(TT), RT combined with ICIs might be the best treatment mode for OS(ICIs+RT vs CT+RT vs TT+RT; 91.9% vs. 27.8% vs. 29.3%, iPFS (ICIs+RT vs CT+RT vs TT+RT, 46.9% vs 25.2% vs 25.6%) and PFS (ICIs+RT vs CT+RT vs TT+RT, 36.2% vs 31% vs 36.5%).ConclusionsRT combined with ICIs might be the best treatment mode to prolong the OS for BMs from NSCLC with non-EGFR mutation/ALK gene rearrangement.Review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022350065, identifier (CRD42022350065).

Project description:BackgroundBrain metastases (BM) from non-small-cell lung cancer (NSCLC) are frequent and carry significant morbidity, and current management options include varying local and systemic therapies. Here, we performed a systematic review and network meta-analysis to determine the ideal treatment regimen for NSCLC BMs with targetable EGFR-mutations/ALK-rearrangements.MethodsWe searched MEDLINE, EMBASE, Web of Science, ClinicalTrials.gov, CENTRAL and references of key studies for randomized controlled trials (RCTs) published from inception until June 2020. Comparative RCTs including ≥10 patients were selected. We used a frequentist random-effects model for network meta-analysis (NMA) and assessed the certainty of evidence using the GRADE approach. Our primary outcome of interest was intracranial progression-free survival (iPFS).ResultsWe included 24 studies representing 19 trials with 1623 total patients. Targeted tyrosine kinase inhibitors (TKIs) significantly improved iPFS, with second-and third- generation TKIs showing the greatest benefit (HR=0.25, 95%CI 0.15-0.40). Overall PFS was also improved compared to conventional chemotherapy (HR=0.47, 95%CI 0.36-0.61). In EGFR-mutant patients, osimertinib showed the greatest benefit in iPFS (HR=0.32, 95%CI 0.15-0.69) compared to conventional chemotherapy, while gefitinib + chemotherapy showed the greatest overall PFS benefit (HR=0.26, 95%CI 0.10-0.70). All ALKi improved overall PFS compared to conventional chemotherapy, with alectinib having the greatest benefit (HR=0.13, 95%CI 0.07-0.24).ConclusionsIn patients with NSCLC BMs and EGFR/ALK mutations, targeted TKIs improve intracranial and overall PFS compared to conventional modalities such as chemotherapy, with greater efficacy seen using newer generations of TKIs. This data is important for treatment selection and patient counseling, and highlights areas for future RCT research.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=179060.

Dataset Information

Efficacy of D5F3 IHC for detecting ALK gene rearrangement in NSCLC patients: a systematic review and meta-analysis.

Publications

Efficacy of D5F3 IHC for detecting ALK gene rearrangement in NSCLC patients: a systematic review and meta-analysis.

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