Concordance of Cytological Specimens with Histological Tissue for Detection of Epidermal Growth Factor Receptor Mutation in Non-Small Cell Lung Cancer: A Systematic Review

2021 ◽  
Vol 66 (1) ◽  
pp. 61-71
Author(s):  
Tzy Harn Chua ◽  
Khoon Leong Chuah

<b><i>Introduction:</i></b> There is increasing need for more testing in non-small cell lung cancer given the introduction of newer targeted therapies. Cytological specimens including conventional smears (CS), cell blocks (CB), and liquid-based cytology (LBC) are an alternative to histologic tissue (HT) specimens in detecting <i>EGFR</i> mutations, but the concordance of these 2 specimens is yet to be determined. The aim of the present systematic review is to determine the concordance rates between different cytologic specimens with HT in detecting <i>EGFR</i> mutations. <b><i>Methods:</i></b> PubMed, Cochrane Library, and Google Scholar were utilized in the primary search, along with reference lists of electronically retrieved full-text articles. Concordance rates were pooled together if 2 or more studies reporting the same type of cytologic specimen were available. <b><i>Results:</i></b> Overall, 15 studies were included in this review, with 13 studies included in the pooled analysis. There was an overall concordance rate of 92.8% in 593 paired cytologic and HT specimens, with LBC having the highest concordance rate of 96.0%, followed by CS and CB, each with a concordance rate of 95.8%, although the concordance rate of CS and/or CB was lower at 90.6% with a larger pool of studies. LBC was found to have a significantly higher concordance rate than CS and/or CB. <b><i>Conclusion:</i></b> Cytological specimens have a high concordance rate in detecting <i>EGFR</i> mutations, when compared to HT. LBC has shown superior concordance rates compared to CS and CB. Cytological specimens should be considered as an additional and alternative source of diagnostic material for <i>EGFR</i> testing.

2022 ◽  
Vol 29 (1) ◽  
pp. 255-266
Author(s):  
Ilaria Attili ◽  
Antonio Passaro ◽  
Pasquale Pisapia ◽  
Umberto Malapelle ◽  
Filippo de Marinis

Compound epidermal growth factor receptor (EGFR) mutations represent a heterogeneous subgroup of non-small cell lung cancer (NSCLC) patients with uncommon EGFR mutations. We conducted a systematic review to investigate the available data on this patients’ subgroup. Overall, we found a high heterogeneity in the incidence of compound mutations (4–26% of total EGFR mutant cases), which is dependent on the different testing methods adopted and the specific mutations considered. In addition, the relative incidence of distinct compound subclasses identified is reported with extreme variability in different studies. Preclinical and clinical data, excluding de novoEGFR exon 20 p.T790M compound mutations, show good responses with EGFR tyrosine kinase inhibitors (TKIs) (combined common mutations: response rate (RR) ≥ 75% with either first- or second-generation TKIs; combined common plus uncommon: RR 40–80% and 100% with first-generation TKIs and afatinib, respectively; combined uncommon: RR 20–70%, ~80% and ~75% with first-generation TKIs, afatinib and osimertinib, respectively). Overall, data are consistent in supporting the use of EGFR TKIs in treating compound EGFR mutations, taking into account different sensitivity profile of accompanying EGFR mutations for selecting the most adequate EGFR TKI for individual patients.


2019 ◽  
Vol 19 (3) ◽  
pp. 199-209 ◽  
Author(s):  
Bing-Di Yan ◽  
Xiao-Feng Cong ◽  
Sha-Sha Zhao ◽  
Meng Ren ◽  
Zi-Ling Liu ◽  
...  

Background and Objective: We performed this systematic review and meta-analysis to assess the efficacy and safety of antigen-specific immunotherapy (Belagenpumatucel-L, MAGE-A3, L-BLP25, and TG4010) in the treatment of patients with non-small-cell lung cancer (NSCLC). </P><P> Methods: A comprehensive literature search on PubMed, Embase, and Web of Science was conducted. Eligible studies were clinical trials of patients with NSCLC who received the antigenspecific immunotherapy. Pooled hazard ratios (HRs) with 95% confidence intervals (95%CIs) were calculated for overall survival (OS), progression-free survival (PFS). Pooled risk ratios (RRs) were calculated for overall response rate (ORR) and the incidence of adverse events. </P><P> Results: In total, six randomized controlled trials (RCTs) with 4,806 patients were included. Pooled results showed that, antigen-specific immunotherapy did not significantly prolong OS (HR=0.92, 95%CI: 0.83, 1.01; P=0.087) and PFS (HR=0.93, 95%CI: 0.85, 1.01; P=0.088), but improved ORR (RR=1.72, 95%CI: 1.11, 2.68; P=0.016). Subgroup analysis based on treatment agents showed that, tecemotide was associated with a significant improvement in OS (HR=0.85, 95%CI: 0.74, 0.99; P=0.03) and PFS (HR=0.70, 95%CI: 0.49, 0.99, P=0.044); TG4010 was associated with an improvement in PFS (HR=0.87, 95%CI: 0.75, 1.00, P=0.058). In addition, NSCLC patients who were treated with antigen-specific immunotherapy exhibited a significantly higher incidence of adverse events than those treated with other treatments (RR=1.11, 95%CI: 1.00, 1.24; P=0.046). </P><P> Conclusion: Our study demonstrated the clinical survival benefits of tecemotide and TG4010 in the treatment of NSCLC. However, these evidence might be limited by potential biases. Therefore, further well-conducted, large-scale RCTs are needed to verify our findings.


Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2265
Author(s):  
Elio Gregory Pizzutilo ◽  
Martino Pedrani ◽  
Alessio Amatu ◽  
Lorenzo Ruggieri ◽  
Calogero Lauricella ◽  
...  

Background: The potential added value of liquid biopsy (LB) is not well determined in the case of small cell lung cancer (SCLC), an aggressive tumor that can occur either de novo or from the histologic transformation of non-small cell lung cancer (NSCLC). Methods: A systematic review of studies adopting LB in patients with SCLC have been performed to assess the clinical utility of circulating tumor DNA (ctDNA) or circulating tumor cells (CTCs). Results: After a screening of 728 records, 62 studies (32 evaluating CTCs, 27 ctDNA, and 3 both) met predetermined eligibility criteria. Only four studies evaluated LB in the diagnostic setting for SCLC, while its prognostic significance was evaluated in 38 studies and prominently supported by both ctDNA and CTCs. A meta-analysis of 11 studies as for CTCs enumeration showed an HR for overall survival of 2.63 (1.71–4.05), with a potential publication bias. The feasibility of tumor genomic profiling and the predictive role of LB in terms of response/resistance to chemotherapy was assessed in 11 and 24 studies, respectively, with greater consistency for those regarding ctDNA. Intriguingly, several case reports suggest that LB can indirectly capture the transition to SCLC in NSCLC treated with EGFR tyrosine kinase inhibitors. Conclusions: While dedicated trials are needed, LB holds potential clinical roles in both de novo and transformed SCLC. CtDNA analysis appears the most valuable and practicable tool for both disease monitoring and genomic profiling.


Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2084
Author(s):  
Roberto Martin-Deleon ◽  
Cristina Teixido ◽  
Carmen Mª Lucena ◽  
Daniel Martinez ◽  
Ainhoa Fontana ◽  
...  

Clinical guidelines promote the identification of several targetable biomarkers to drive treatment decisions in advanced non-small cell lung cancer (NSCLC), but half of all patients do not have a viable biopsy. Specimens from endobronchial-ultrasound transbronchial needle aspiration (EBUS-TBNA) are an alternative source of material for the initial diagnosis of NSCLC, however their usefulness for a complete molecular characterization remains controversial. EBUS-TBNA samples were prospectively tested for several biomarkers by next-generation sequencing (NGS), nCounter, and immunohistochemistry (PD-L1). The primary objectives were to assess the sensitivity of EBUS-TBNA samples for a comprehensive molecular characterization and to compare its performance to the reference standard of biopsy samples. Seventy-two EBUS-TBNA procedures were performed, and 42 NSCLC patients were diagnosed. Among all cytological samples, 92.9% were successfully genotyped by NGS, 95.2% by nCounter, and 100% by immunohistochemistry. There were 29 paired biopsy samples; 79.3% samples had enough tumor material for genomic genotyping, and 96.6% for PD-L1 immunohistochemistry. A good concordance was found between both sources of material: 88.9% for PD-L1, 100% for NGS and nCounter. EBUS-TBNA is a feasible alternative source of material for NSCLC genotyping and allows the identification of patient candidates for personalized therapies with high concordance when compared with biopsy.


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