Molecular Testing for Targeted Therapy in Advanced Non–Small Cell Lung Cancer: Suitability of Endobronchial Ultrasound Transbronchial Needle Aspiration

Casadio, Chiara; Guarize, Juliana; Donghi, Stefano; Tonno, Clementina Di; Fumagalli, Caterina; Vacirca, Davide; Dell’Orto, Patrizia; Marinis, Filippo de; Spaggiari, Lorenzo; Viale, Giuseppe; Barberis, Massimo

doi:10.1309/ajcpxgraimb4ctq3

Cited by 63 publications

(53 citation statements)

References 30 publications

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“…Conversely, ALK (6.4%) rearrangements were more frequently identified in young female and never-smoker patients, confirming that different clinical characteristics are often associated with different molecular alterations 39. Comparing the present results to those obtained in our previous NSCLC series,30 we found concordant frequencies of KRAS alterations but significantly higher rates of ALK translocated tumours (present series 6.4% vs historical series 3.5%; p-value <0.005). This might be due to both the implementation of immunohistochemistry as an adjunct tool in ambiguous ALK FISH test results40 and the recent approval (January 2017) of crizotinib as first-line therapy for ALK-translocated NSCLC by the Agenzia Italiana del Farmaco (AIFA) that increased the number of ALK test orders.…”

Section: Discussionsupporting

confidence: 84%

“…Level I alterations in EGFR and/or KRAS were present in 286 non-squamous NSCLC, including 2 cases with concurrent EGFR and KRAS mutations. In the present series, we found a significantly higher percentage of EGFR -mutated patients than our previously published historical series analysed with Sanger sequencing or real-time-based assays30 (present series 22.4% vs historical series 15.1%; p value <0.005). This could be related to the higher sensitivity of the current NGS analysis; however, we adopted a threshold of variant calls of 5% that is comparable with the sensitivity of the real-time assay used in the previous study 31.…”

Section: Discussioncontrasting

confidence: 60%

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The long tail of molecular alterations in non-small cell lung cancer: a single-institution experience of next-generation sequencing in clinical molecular diagnostics

et al. 2018

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BackgroundMolecular profiling of advanced non-small cell lung cancers (NSCLC) is essential to identify patients who may benefit from targeted treatments. In the last years, the number of potentially actionable molecular alterations has rapidly increased. Next-generation sequencing allows for the analysis of multiple genes simultaneously.AimsTo evaluate the feasibility and the throughput of next-generation sequencing in clinical molecular diagnostics of advanced NSCLC.MethodsA single-institution cohort of 535 non-squamous NSCLC was profiled using a next-generation sequencing panel targeting 22 actionable and cancer-related genes.Results441 non-squamous NSCLC (82.4%) harboured at least one gene alteration, including 340 cases (63.6%) with clinically relevant molecular aberrations. Mutations have been detected in all but one gene (FGFR1) of the panel. Recurrent alterations were observed in KRAS, TP53, EGFR, STK11 and MET genes, whereas the remaining genes were mutated in <5% of the cases. Concurrent mutations were detected in 183 tumours (34.2%), mostly impairing KRAS or EGFR in association with TP53 alterations.ConclusionsThe study highlights the feasibility of targeted next-generation sequencing in clinical setting. The majority of NSCLC harboured mutations in clinically relevant genes, thus identifying patients who might benefit from different targeted therapies.

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Section: Discussionsupporting

confidence: 84%

Section: Discussioncontrasting

confidence: 60%

The long tail of molecular alterations in non-small cell lung cancer: a single-institution experience of next-generation sequencing in clinical molecular diagnostics

et al. 2018

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“…The clinical importance of molecular testing is well established. The debate regarding the adequacy of cytological versus histologic samples for molecular testing is ongoing [16] , but to date, studies have demonstrated excellent results for the detection of EGFR and ALK mutations with EBUS-TBNA [21,22] . The result of our data echoes the findings in previous studies with 100% of the samples from adenocarcinoma satisfactory for EGFR and ALK testing.…”

Section: Discussionmentioning

confidence: 99%

Flexible 19-Gauge Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Needle: First Experience

Tyan

Patel²,

Czarnecka³

et al. 2017

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Background: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a well-established first-line invasive modality for mediastinal lymph node staging in lung cancer patients and in the diagnostic workup of patients with mediastinal adenopathy. With the current 21- and 22-gauge (G) EBUS-TBNA needles, the procedure can be limited by the degree of flexibility in the needle and the size of the lumen in tissue acquisition. Objective: We report our initial experience with a first-generation flexible 19-G EBUS-TBNA (Flex 19G; Olympus Respiratory America, Redmond, WA, USA) needle with regards to efficacy and safety. Methods: The Flex 19G EBUS-TBNA needle was used in 47 selected patients with enlarged hilar and/or mediastinal lymphadenopathy at 3 centers. The standard Olympus EBUS scope with a 2.2-mm working channel was used in all cases. Results: The diagnostic yield of the Flex 19G needle according to clinical cytopathology reports was 89% (42/47). The diagnosis and their respective diagnostic yield with the Flex 19G EBUS-TBNA needle were malignancy 24/27 (89%), sarcoidosis 13/14 (93%), and reactive lymph node hyperplasia 5/6 (83%). The mean short axis of the sampled lymph nodes was 19 ± 9 mm. No complications occurred except for 1 instance of moderate bleeding, which did not require intervention beyond suctioning and subsequently resolved. All 13 patients diagnosed with adenocarcinoma by the 19-G needle had sufficient tissue for genetic testing. Conclusion: EBUS-TBNA using the first-generation Flex 19G needle is feasible and safe with promising diagnostic yield while providing a greater degree of flexion with the Olympus EBUS scope. Additional clinical evaluations are warranted.

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“…The success in performing molecular tests on TBNA samples depends on the absolute number and percentage of malignant cells present in the sampled material, on quality of cell preservation and on type and sensitivity of the test itself (17,39). Recent reports from high-volume centers indicate that 72-97% of EBUS-TBNA samples are appropriate for testing the most frequently used prognostic markers of lung cancer, namely EGFR, ALK and KRAS (17,25,39,40). Both smear and cell block preparation, or core tissue, can be utilized for molecular testing (17,23); however, while EGFR and KRAS status can be determined using all three specimen preparation techniques, the ALK translocation is best assessed using cell block and core tissue (17).…”

Section: Molecular Testingmentioning

confidence: 99%

Endobronchial ultrasound-transbronchial needle aspiration for mediastinal staging of non-small cell lung cancer: variability of results and perspectives

2017

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The remarkable value of endobronchial ultrasound-transbronchial needle aspiration (EBUS-TBNA) for mediastinal staging of non-small cell lung cancer (NSCLC) is recognized worldwide.Reports from different centers however show considerable variation of EBUS-TBNA performance in terms of diagnostic yield, sensitivity and negative predictive value (NPV). Interpretation of EBUS-TBNA diagnostic efficacy requires clarifying whether the technique is used for purely diagnostic purpose or mediastinal staging, recognizing that different study groups may be inherently heterogeneous and that numerous factors may impact on the procedure outcomes. Review of these factors indicates that the prevalence of N2/N3 disease, the thoroughness of mediastinal sampling and >3 needle passes per target lymph node (LN) [in the absence of rapid on-site evaluation (ROSE)] influence the procedure outcomes, while many details in the sample preparation technique are unlikely to impact on the results and should be left to the proceduralists' preference. Generalized use of a standardized database for prospective collection of relevant EBUS-TBNA data would allow reporting institutional results by subgroups of N2/N3 disease prevalence and thoroughness of staging, and would help establishing quality standards for the procedure.

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Molecular Testing for Targeted Therapy in Advanced Non–Small Cell Lung Cancer: Suitability of Endobronchial Ultrasound Transbronchial Needle Aspiration

Abstract: Our study demonstrates that EBUS-TBNA can be effectively used not just for diagnosis but also for complete mutational testing.

Cited by 63 publications

References 30 publications

The long tail of molecular alterations in non-small cell lung cancer: a single-institution experience of next-generation sequencing in clinical molecular diagnostics

The long tail of molecular alterations in non-small cell lung cancer: a single-institution experience of next-generation sequencing in clinical molecular diagnostics

Flexible 19-Gauge Endobronchial Ultrasound-Guided Transbronchial Needle Aspiration Needle: First Experience

Endobronchial ultrasound-transbronchial needle aspiration for mediastinal staging of non-small cell lung cancer: variability of results and perspectives

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