EGFR Mutation Testing in Patients with Non-Small Cell Lung Cancer in Routine Clinical Practice

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dc.contributor.advisor Tin, T en
dc.contributor.advisor Elwood, M en Thi, Aye Myat en 2018-11-01T20:27:24Z en 2018 en
dc.identifier.uri en
dc.description Full text is available to authenticated members of The University of Auckland only. en
dc.description.abstract Background: Epidermal Growth Factor Receptor (EGFR) mutation testing is recommended as an essential addition to the assessment algorithm in patients with non-squamous, non-small cell lung cancer (NSCLC) to inform targeted treatment, but not all eligible patients receive testing. Aim: This thesis has two parts. Part I aims to review the available evidence on the prevalence of EGFR mutation testing in routine care settings, associated factors and its impact on disease management in patients with NSCLC. Part II aims to identify the determinants of EGFR mutation testing in patients with non-squamous NSCLC in Northern New Zealand, particularly across different patient subgroups defined by age, gender, ethnicity, histology, disease extent and diagnostic period, and to examine the impact of incomplete testing on estimating EGFR mutation prevalence. Methods: In part I, five electronic databases, Web of science, Medline (Ovid), Science Direct, Embase and Scopus were searched. Bibliographies of relevant articles, studies which cited already included studies, and certain cancer websites were also checked. Studies were eligible to be included if they (i) reported the uptake of EGFR testing in NSCLC patients; (ii) were conducted in the routine clinical practice; (iii) were published in English prior to July 2017; and (iv) had full text available. The studies were appraised using the STROBE and the NIH (National Heart, Lung and Blood Institute) checklists and the findings were reported according to the PRISMA Statement. In part II, a retrospective analysis was undertaken using the data from a population-based cohort of patients who were diagnosed with non-squamous NSCLC in four Northern district health boards (DHBs) between January 2010 and July 2016. Eligible patients were identified from the New Zealand Cancer Registry (NZCR) and demographic and clinico-pathological data were extracted. Information on EGFR mutation testing was obtained through a linkage to laboratory records and TestSafe data. Multivariate logistic regressions were performed to examine factors associated with EGFR mutation testing. Log-linear models were used to assess the association between testing prevalence and mutation prevalence. Results In part I, a total of 6403 records were identified and 4747 records were reviewed. Eighteen articles published between 2011 and 2017 were included in the review. Testing prevalence varied widely between 9.6% and 78.3 %. Of the ten studies that reported time trends, nine (US, Korea, Canada and New Zealand) reported an increasing trend. Females, younger age, former smokers, advanced stage, adenocarcinoma, better mobility, radiation therapy, private insurance and low deprivation were significantly associated with an increased rate of testing/request for testing. The tested patients had shorter waiting time for appropriate treatment, were more likely to be treated with and respond to targeted therapy and had better survival than those not tested. In part II, 43% of NSCLC patients had their EGFR mutations determined in New Zealand between 2010 and 2016. Younger age (≤ 59 years), Asians, residence in affluent neighbourhood, adenocarcinoma histology, diagnosis by histology basis, tumour in upper lobe, locally advanced/metastatic disease and diagnosis in the most recent period were significantly associated with increased testing. Determinants of testing were mostly similar across patient subgroups except for some significant differences. Older patients had lower testing in the adenocarcinoma group and patients with distal spread while there were no such associations in the non-adenocarcinoma group and patients without distal spread. Associations with higher testing in Asians compared to NZ Europeans were stronger in the non-adenocarcinoma group. Disease in the main bronchus (compared to the upper lobe) was associated with lower testing in younger patients and the nonadenocarcinoma group but associated with higher testing in older patients and the adenocarcinoma group. Throughout the study period, inequalities in testing by neighbourhood deprivation became more pronounced over time while selection by disease extent was reduced. Testing was remarkably increased over the study period. The log-linear models showed a significant inverse association between testing prevalence and mutation prevalence. The mutation prevalence, if all patients were tested, was estimated to be 13.7% (cf. 21.6% in patients who were tested). Conclusion The testing prevalence varied widely but increased over time. Both the review of international literature and the NZ study showed that testing was selective and influenced by several demographic, biological and socioeconomic factors, and had a positive impact on clinical management and outcomes of patients with NSCLC. Mostly, factors associated with testing were similar in subgroups, but effects of old age, Asian ethnicity and location in the main bronchus were different in groups by age, histology and disease extent. Between 2010 and 2016, NZ saw an improvement in differential selection by disease extent whereas selection by neighbourhood deprivation became increased. Reported mutation prevalence which did not account for incomplete testing may not be accurate. en
dc.publisher ResearchSpace@Auckland en
dc.relation.ispartof Masters Thesis - University of Auckland en
dc.relation.isreferencedby UoA99265083514002091 en
dc.rights Items in ResearchSpace are protected by copyright, with all rights reserved, unless otherwise indicated. Previously published items are made available in accordance with the copyright policy of the publisher. en
dc.rights.uri en
dc.title EGFR Mutation Testing in Patients with Non-Small Cell Lung Cancer in Routine Clinical Practice en
dc.type Thesis en Public Health en The University of Auckland en Masters en
dc.rights.holder Copyright: The author en
pubs.elements-id 755465 en
pubs.record-created-at-source-date 2018-11-02 en

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