Molecular Profiling of Malignant Pleural Effusion in Metastatic Non-Small Cell Lung Carcinoma: The Effect of Pre-analytical Factors

Carter, Jamal; Miller, James A.; Feller‐Kopman, David; Ettinger, David S.; Sidransky, David; Maleki, Zahra

doi:10.1513/annalsats.201609-709oc

Cited by 42 publications

(52 citation statements)

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“…This has been expanded, primarily due to the availability of IHC/immunocytochemistry, and, more recently, by performing other ancillary techniques such as molecular studies and identifying specific biomarkers such as PD-L1 on cytologic material [3, 12, 16-18]. However, obtaining adequate material to perform all the studies necessary to diagnose and guide therapy is still a challenge.…”

Section: Discussionmentioning

confidence: 99%

The Differential Diagnosis in Nonlymphoproliferative Malignant Pleural Effusion Cytopathology and Its Correlation with Patients’ Demographics

2018

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Background: We report our experience with malignant pleural effusion (MPE) and the impact of patients’ demographics on the differential diagnosis at the primary site. Methods: After IRB approval, we searched our pathology database from January 2013 to January 2017 for patients with positive pleural effusions (PEs). Patients’ demographics and clinical histories were noted. Results: 474 patients were identified (288 females [61%] and 186 males [39%]), ranging in age from 19 to 64 years old. Ethnicity was distributed as follows: Caucasian (n = 330, 70%), African American (n = 114, 24%) and Asian (n = 30, 6%). The most common primary sites were the lung (n = 180, 37%), followed by the breast (n = 81, 17%), and the gynecologic system (67, 13%). The lung was the most common primary for all ethnicities (n = 190, 40%). The second-most common primary site was the breast in African Americans and Caucasians and upper gastrointestinal (GI) tract in Asians. In 5 cases (1%), the primary tumor could not be determined. Conclusion: Cytology examination is a useful method to diagnose primary sites of PE. Pulmonary primary is the most common cause of effusion in all ethnicities. In African American and Caucasian patients, the breast was the second-most common site of MPE, while in Asian patients it was the upper GI tract.

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Section: Discussionmentioning

confidence: 99%

The Differential Diagnosis in Nonlymphoproliferative Malignant Pleural Effusion Cytopathology and Its Correlation with Patients’ Demographics

2018

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“…MPE could be used to detect the presence of EGFR mutations, especially when there is not enough tissue available for mutational analysis. The results of the main studies assessing the feasibility of detection of EGFR mutations in MPE are summarized in Table …”

Section: Implications Of New Therapies In Nsclcmentioning

confidence: 99%

“…Only small series are available. In the series published, the most common genetic aberrations identified were EGFR, KRAS mutations and ALK translocation . A Chinese study analysed the clinical and prognostic implications of RET rearrangements in metastatic lung adenocarcinoma patients with MPE.…”

Section: Implications Of New Therapies In Nsclcmentioning

confidence: 99%

“…The results of the main studies assessing the feasibility of detection of EGFR mutations in MPE are summarized in Table 1. [27][28][29][30][31][32][33][34] The quality of the MPE samples is essential to improve quantity and quality of tumour cells for mutational analysis. After enrichment of pleural fluid, 27 the percentage of the tumour cells in MPE was increased from 0.64% to 40.8%.…”

Section: Egfr Mutationsmentioning

confidence: 99%

“…In the series published, the most common genetic aberrations identified were EGFR, KRAS mutations and ALK translocation. 28 52 Another Chinese group reported interesting cases of lung adenocarcinomas with MET amplification in pleural effusion which rapidly responded to crizotinib after EGFR-TKI acquired resistance. 53 Peptid nucleic acid-mediated RT-PCR has a good diagnostic accuracy to detect KRAS mutation in pleural effusion.…”

Section: Future Directionsmentioning

confidence: 99%

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Novel insights into the systemic treatment of lung cancer malignant pleural effusion

Tissot

Gay

Brun

et al. 2019

Clinical Respiratory J

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Lung cancer is the most common fatal malignancy worldwide. Approximately 75% of non‐small‐cell lung cancer (NSCLC) patients are diagnosed at an advanced or a metastatic stage. Since 2007, NSCLC patients with malignant pleural effusion (MPE) are staged as M1 disease. During the last decades, chemotherapeutic agents failed to offer a significant improvement of survival in patients with metastatic disease. The current review aims to summarize the actual situation of the recently developed therapies in patients with lung cancer and MPE.

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Testing for EGFR Variants in Pleural and Pericardial Effusion Cell-Free DNA in Patients With Non–Small Cell Lung Cancer

Lee

Gai

et al. 2023

JAMA Oncol

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ImportanceMolecular testing in non–small cell lung cancer (NSCLC) is commonly limited by inadequate tumor sample. Plasma cell-free DNA (cfDNA) genotyping as a complementary test is specific but only moderately sensitive. Genotyping of cfDNA in pleural and pericardial effusion (PE-cfDNA) can further optimize molecular diagnostic yield and reduce the need for repeated biopsies.ObjectiveTo prospectively validate droplet digital polymerase chain reaction (ddPCR) for detection of sensitizing EGFR variants and acquired Thr790Met variant (T790M) from PE-cfDNA in patients with NSCLC.Design, Setting, and ParticipantsThis prospective diagnostic validation study was conducted between September 6, 2016, and January 21, 2021 at 2 major Hong Kong cancer centers. Patients with advanced NSCLC with both wild-type and variant EGFR status and exudative PE who underwent thoracocentesis or pericardiocentesis were randomly enrolled. Patients were either EGFR-tyrosine kinase inhibitor (TKI) naive (cohort 1) or EGFR-TKI treated but osimertinib naive (cohort 2). Enrolled patients underwent pleural- or pericardial-fluid and blood sampling for ddPCR EGFR testing. EGFR status results with ddPCR testing of PE-cfDNA and blood were compared with EGFR status in matched tumor biopsy or PE cell block samples.Main Outcomes and MeasuresSpecificity, sensitivity, and concordance of PE-cfDNA for detection of sensitizing EGFR variants and acquired T790M variation.ResultsAmong 171 patients (54% female) enrolled, there were 104 in cohort 1 and 67 in cohort 2. In cohort 1, 37% (38/102) were EGFR-variant positive; PE-cfDNA showed 97% sensitivity (95% CI, 92%-100%), 97% specificity (95% CI, 93%-100%), and 97% concordance (ĸ = 0.94, P &lt; .001) for the detection of sensitizing EGFR variants. It was more sensitive than plasma in detecting sensitizing EGFR variants (97% vs 74%, P &lt; .001). In cohort 2, 38% (15 of 40) were positive for the EGFR T790M variant; PE-cfDNA showed 87% sensitivity (95% CI, 69%-100%), 60% specificity (95% CI, 41%-79%), and 70% concordance (ĸ = 0.42, P = .004) for acquired T790M. The EGFR T790M variant was detected in 51% of PE-cfDNA vs 25% of PE cell block samples.Conclusions and RelevanceIn this diagnostic study, EGFR variants could be accurately detected from PE-cfDNA in patients with NSCLC. More EGFR T790M was detected in PE-cfDNA than in guideline-recommended PE cell block preparations. These results suggest that PE-cfDNA can complement plasma and tumor genotyping for detecting EGFR variants in patients with advanced NSCLC.

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Molecular Profiling of Malignant Pleural Effusion in Metastatic Non-Small Cell Lung Carcinoma: The Effect of Pre-analytical Factors

Abstract: Molecular profiling of MPE is a viable alternative to testing solid tissue in NSCLC. This study shows successful detection of genetic aberrations in 59% of samples with minimal risk of false negative.

Cited by 42 publications

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The Differential Diagnosis in Nonlymphoproliferative Malignant Pleural Effusion Cytopathology and Its Correlation with Patients’ Demographics

The Differential Diagnosis in Nonlymphoproliferative Malignant Pleural Effusion Cytopathology and Its Correlation with Patients’ Demographics

Novel insights into the systemic treatment of lung cancer malignant pleural effusion

Testing for EGFR Variants in Pleural and Pericardial Effusion Cell-Free DNA in Patients With Non–Small Cell Lung Cancer

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