Rate of Egfr Mutation Testing for Patients with Nonsquamous Non-Small-Cell Lung Cancer with Implementation of Reflex Testing by Pathologists

Cheema, Parneet K.; Raphael, Simon; El-Maraghi, Robert H.; Li, J; McClure, Rebecca F.; Zibdawi, L.; Chan, Adrien; Victor, J. Charles; Dolley, A; Dziarmaga, Alison

doi:10.3747/co.24.3266

Cited by 29 publications

(20 citation statements)

References 20 publications

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“…In our observational study, as expected according to results of randomised trials (Mok et al, 2009;Shaw et al, 2013) T A B L E 4 Relation between ALK status and clinicopathologic features in patients with advanced non-squamous NSCLC According to previous studies long turnaround times for test results were one of the main barriers to EGFR testing as oncologists and patients were both anxious of clinical deterioration during that time (Spicer, Tischer, & Peters, 2015). Although higher testing rates and shorter time to-treatment decisions and treatment can be achieved with reflex testing (Cheema et al, 2015(Cheema et al, , 2017Lim et al, 2015), a…”

Section: Discussionsupporting

confidence: 60%

Epidermal growth factor receptor and anaplastic lymphoma kinase testing and mutation prevalence in patients with advanced non-small cell lung cancer in Switzerland: A comprehensive evaluation of real world practices

et al. 2017

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In order to improve outcomes, identification of the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) genes has become crucial in advanced non-small-cell lung cancer (NSCLC). The aim of the present study is to analyse time trends and frequency of testing, factors affecting testing as well as prevalence of mutations in the Swiss population. We analysed EGFR and ALK testing in a cohort of patients with newly diagnosed metastasised non-squamous NSCLC in the catchment area of the cancer registry Eastern Switzerland in the years 2008-2014. We analysed prevalence of mutations and studied clinicopathological characteristics and survival of tested and non-tested patients and of patients with and without mutations. Among 718 patients identified, 11% (51/447) harboured an EGFR mutation in the exons 18, 19 or 21 and further 12% (31/265) showed a positive test result for ALK rearrangements. In non-smokers the proportions of mutations were 31% and 23% respectively. Testing rates increased over time and reached 79% in 2014. We observed significantly lower testing rates and poorer survival in elderly, patients with limited life expectancy and patients treated at hospitals not involved in clinical research. Outcomes can be further improved in a considerable proportion of patients with advanced non-squamous NSCLC.

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Section: Discussionsupporting

confidence: 60%

Epidermal growth factor receptor and anaplastic lymphoma kinase testing and mutation prevalence in patients with advanced non-small cell lung cancer in Switzerland: A comprehensive evaluation of real world practices

et al. 2017

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“…The accumulation of genetic aberrations over time has been recognized as the main cause of cancer [ 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ]. A combination of genetic mutations and epigenetic alterations results in tumor heterogeneity [ 67 , 71 , 72 , 73 , 74 , 75 , 76 , 77 ].…”

Section: Cancer Cell Chemoresistancementioning

confidence: 99%

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

Senthebane

Rowe

Thomford

et al. 2017

IJMS

340

330

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Chemoresistance is a leading cause of morbidity and mortality in cancer and it continues to be a challenge in cancer treatment. Chemoresistance is influenced by genetic and epigenetic alterations which affect drug uptake, metabolism and export of drugs at the cellular levels. While most research has focused on tumor cell autonomous mechanisms of chemoresistance, the tumor microenvironment has emerged as a key player in the development of chemoresistance and in malignant progression, thereby influencing the development of novel therapies in clinical oncology. It is not surprising that the study of the tumor microenvironment is now considered to be as important as the study of tumor cells. Recent advances in technological and analytical methods, especially ‘omics’ technologies, has made it possible to identify specific targets in tumor cells and within the tumor microenvironment to eradicate cancer. Tumors need constant support from previously ‘unsupportive’ microenvironments. Novel therapeutic strategies that inhibit such microenvironmental support to tumor cells would reduce chemoresistance and tumor relapse. Such strategies can target stromal cells, proteins released by stromal cells and non-cellular components such as the extracellular matrix (ECM) within the tumor microenvironment. Novel in vitro tumor biology models that recapitulate the in vivo tumor microenvironment such as multicellular tumor spheroids, biomimetic scaffolds and tumor organoids are being developed and are increasing our understanding of cancer cell-microenvironment interactions. This review offers an analysis of recent developments on the role of the tumor microenvironment in the development of chemoresistance and the strategies to overcome microenvironment-mediated chemoresistance. We propose a systematic analysis of the relationship between tumor cells and their respective tumor microenvironments and our data show that, to survive, cancer cells interact closely with tumor microenvironment components such as mesenchymal stem cells and the extracellular matrix.

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“…Reflex testing is standard practice with other solid tumor types: ASCO/CAP breast cancer guidelines state that reflex testing must be conducted when human EGFR 2 (HER2) IHC results are equivocal (66). Real-world advantages of reflex testing include an increase in the number of patients being tested for molecular targets such as EGFRm, reduction in turnaround time to treatment due to early availability of test results, and increased quality of biomarker testing, with fewer unsuccessful tests (67,68). It is therefore likely that widespread implementation of reflex testing in the NSCLC setting would ensure molecular results are available early, allowing for selection of the most appropriate therapy.…”

Section: Strategies For Optimizing Molecular Testing In Advanced Nsclcmentioning

confidence: 99%

Molecular testing strategies in non-small cell lung cancer: optimizing the diagnostic journey

Gregg

Yoneda

2019

Transl. Lung Cancer Res

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Molecular testing identifies patients with advanced non-small cell lung cancer (NSCLC) who may benefit from targeted therapy or immunotherapy (i.e., immune checkpoint inhibitor treatment for patients with high tumor mutational burden (TMB), microsatellite instability-high or mismatch repairdeficient tumors). Current guidelines state that molecular testing should be conducted at the time of initial diagnosis and tumor progression on targeted therapy. In real-world clinical practice in the United States (US), molecular testing is often not conducted or happens late in the diagnostic journey, resulting in delayed or inappropriate treatment. Herein, we review the rationale for molecular testing in advanced NSCLC, along with best-practice guidelines based on published recommendations and our own clinical experience, including a case study. We propose three strategies to optimize molecular testing in newly diagnosed patients with advanced NSCLC: (I) pulmonologists, interventional radiologists, or thoracic surgeons order molecular tests as soon as advanced NSCLC with an adenocarcinoma component is suspected; (II) liquid biopsies conducted early in the diagnostic pathway; and (III) pathologist-directed reflex testing, as conducted in other areas of oncology. To help facilitate these strategies, we outline our recommendations for optimal sample collection techniques and stewardship. In summary, we believe that implementation of these individual strategies will allow clinicians to effectively leverage available treatment options for advanced NSCLC, reducing the time to optimal treatment and improving patient outcomes.

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Rate of Egfr Mutation Testing for Patients with Nonsquamous Non-Small-Cell Lung Cancer with Implementation of Reflex Testing by Pathologists

Abstract: Background Testing for mutation of the EGFR (epidermal growth factor receptor) gene is a standard of care for

Cited by 29 publications

References 20 publications

Epidermal growth factor receptor and anaplastic lymphoma kinase testing and mutation prevalence in patients with advanced non-small cell lung cancer in Switzerland: A comprehensive evaluation of real world practices

Epidermal growth factor receptor and anaplastic lymphoma kinase testing and mutation prevalence in patients with advanced non-small cell lung cancer in Switzerland: A comprehensive evaluation of real world practices

The Role of Tumor Microenvironment in Chemoresistance: To Survive, Keep Your Enemies Closer

Molecular testing strategies in non-small cell lung cancer: optimizing the diagnostic journey

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