Beyond Conventional: The New Horizon of Targeted Therapy for the Treatment of Advanced Non Small Cell Lung Cancer

Tartarone, Alfredo; Lapadula, Vittoria; Micco, Concetta Di; Rossi, Gemma; Ottanelli, Carlotta; Marini, Alessandro; Giorgione, Roberta; Ferrari, Katia; Catalano, Martina; Voltolini, Luca; Mini, Enrico; Roviello, Giandomenico

doi:10.3389/fonc.2021.632256

Cited by 11 publications

(5 citation statements)

References 44 publications

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“…Over the last years precision medicine has significantly improved patient outcomes for NSCLC adenocarcinoma and for an increasing amount of targets molecular testing is considered useful [ 15 ]. Although NGS can be used to analyze many genes at once and the DNA quantity required per gene analyzed is low, a threshold quantity of DNA is required for NGS that depends on the NGS panel and platform used [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Short report: Performance evaluation of the Idylla™ KRAS and EGFR mutation tests on paraffin-embedded cytological NSCLC samples

et al. 2021

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Background Quick and reliable testing of EGFR and KRAS is needed in non-small cell lung cancer (NSCLC) to ensure optimal decision-making for targeted therapy. The Idylla™ platform was designed for Formalin-Fixed Paraffin-Embedded (FFPE) tissue sections but recently several studies were published that evaluated its potential for cytological specimens. This study aimed to validate the Idylla™ platform for the detection of EGFR/KRAS mutations in cytological NSCLC samples prepared as cytoblocks using AGAR and paraffin embedding. Material and methods The KRAS Idylla™ test were performed on 11 specimens with a known KRAS mutation. The EGFR Idylla™ test was performed on 18 specimens with a known primary EGFR mutation and 7 specimens with a primary EGFR-EGFR T790M resistance mutation combination. Results Concordant KRAS and primary EGFR mutations were detected for both KRAS and primary EGFR mutations. Samples with a total CQ value of < 26 could be considered negative. Samples with a total CQ value of > 26 could not be assessed (probability of false-negative). In specimens with a primary EGFR-EGFR T790M resistance mutation combination, 5/7 cases were not concordant. Conclusion Our results confirm the conclusion of recent reports that the Idylla™EGFR assay is not suitable in a resistance to EGFR TKI setting, also not in our cytological NSCLC samples prepared as cytoblocks using AGAR and paraffin embedding. KRAS and primary EGFR mutations were detected using the Idylla™ assays in virtually all cytological NSCLC samples. This analysis was rapid and time-saving compared to other mutation detection assays and may be useful if the amount of material is insufficient to perform a full set of molecular tests.

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Section: Discussionmentioning

confidence: 99%

Short report: Performance evaluation of the Idylla™ KRAS and EGFR mutation tests on paraffin-embedded cytological NSCLC samples

et al. 2021

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“…The most frequent oncogenic driver in NSCLC is the Kirsten rat sarcoma viral oncogene (KRAS), which is present in up to 40% of all cases, with the most common mutations being G12C, G12V, and G12D (6). KRAS mutations are associated with worse outcomes after chemotherapy and radiotherapy, with shorter OS in stage III and IV patients (7)(8)(9)(10)(11)(12)(13)(14).…”

Section: Introductionmentioning

confidence: 99%

Assessing the prognostic value of KRAS mutation combined with tumor size in stage I-II non-small cell lung cancer: a retrospective analysis

Eklund,

Mourad,

Wiel

et al. 2024

Front. Oncol.

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BackgroundKRAS mutation status is a well-established independent prognostic factor in advanced non-small cell lung cancer (NSCLC), yet its role in early-stage disease is unclear. Here, we investigate the prognostic value of combining survival data on KRAS mutation status and tumor size in stage I-II NSCLC.MethodsWe studied the combined impact of KRAS mutational status and tumor size on overall survival (OS) in patients with stage I-II NSCLC. We performed a retrospective study including 310 diagnosed patients with early (stage I-II) NSCLCs. All molecularly assessed patients diagnosed with stage I-II NSCLC between 2016–2018 in the Västra Götaland Region of western Sweden were screened in this multi-center retrospective study. The primary study outcome was overall survival.ResultsOut of 310 patients with stage I-II NSCLC, 37% harbored an activating mutation in the KRAS gene. Our study confirmed staging and tumor size as prognostic factors. However, KRAS mutational status was not found to impact OS and there was no difference in the risk of death when combining KRAS mutational status and primary tumor size.ConclusionsIn our patient cohort, KRAS mutations in combination with primary tumor size did not impact prognosis in stage I-II NSCLC.

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“…The most frequent oncogenic driver in NSCLC is the Kirsten rat sarcoma viral oncogene (KRAS), which is present in up to 40% of all cases, with the most common mutations being G12C, G12V, and G12D [6]. KRAS mutations are associated with worse outcomes after chemotherapy and radiotherapy, with shorter OS in stage III and IV patients [7][8][9][10][11][12][13][14].…”

Section: Introductionmentioning

confidence: 99%

“…During the last decade, NSCLC treatment has increasingly depended on molecular profiling given the introduction of small molecule kinase inhibitors (SMKIs) targeting activating mutations in EGFR, ALK, BRAF, RET, MET, NTRK and ROS1 oncogenes and with additional molecular targets pending approval [15]. While only around a third of patients harbour these mutations, the most frequent oncogenic driver in NSCLC is the Kirsten rat sarcoma viral oncogene (KRAS) present in up to 40% of all cases, with the most common mutations being G12C, G12V and G12D [16]. KRAS mutations have been associated with a worse outcome, both when treated with chemotherapy and radiotherapy, with shorter OS in stage III and IV patients [17][18][19][20][21][22][23][24].…”

mentioning

confidence: 99%

Combined assessment ofKRASmutational status and tumor size has no impact on prognosis in early-stage non-small cell lung cancer

Eklund

Mourad

Wiel

et al. 2023

Preprint

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Purpose: The aim of this study it to investigate the combined impact of KRAS mutational status and tumor size on overall survival and risk of death in stage I and II NSCLC. Methods: All consecutive patients molecularly assessed and diagnosed between 2016-2018 with stage I-II NSCLC in the region of West Sweden were included in this multi-center retrospective study. Primary study outcome was overall survival (OS) and risk of death (HR). Results: Out of 310 Stage I-II NSCLC patients, 37% harbored an activating mutation in the KRAS gene (KRASMUT). Our study confirmed staging and tumor size as prognostic factors. KRAS mutational status was not found to impact overall survival and no difference in risk of death was observed when combining KRAS mutational status and primary tumor size. Conclusions: KRAS mutations in combination with primary tumor size are not associated with a worse prognosis in stage I and II NSCLC.

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Beyond Conventional: The New Horizon of Targeted Therapy for the Treatment of Advanced Non Small Cell Lung Cancer

Cited by 11 publications

References 44 publications

Short report: Performance evaluation of the Idylla™ KRAS and EGFR mutation tests on paraffin-embedded cytological NSCLC samples

Short report: Performance evaluation of the Idylla™ KRAS and EGFR mutation tests on paraffin-embedded cytological NSCLC samples

Assessing the prognostic value of KRAS mutation combined with tumor size in stage I-II non-small cell lung cancer: a retrospective analysis

Combined assessment ofKRASmutational status and tumor size has no impact on prognosis in early-stage non-small cell lung cancer

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