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Biopsy on progression in patients with EGFR mutation-positive advanced non-small-cell lung cancer-a Canadian experience.

ABSTRACT: Background:Epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis) are standard therapy for patients with advanced or metastatic non-small-cell lung cancer harbouring an EGFR mutation. Upon progression, 50%-60% develop a secondary T790M mutation. Recent trials demonstrated outcome improvement with osimertinib compared with standard platinum-based chemotherapy as second-line therapy for patients with secondary T790M mutation. To identify T790M, a biopsy of the tumour or, more recently, plasma is necessary. This retrospective study aimed to evaluate biopsy procedures and mutational analysis at 2 Canadian cancer centres. Methods:In a retrospective review of patients who were approached to enrol in the aura2, aura3, or astris studies, demographics, eligibility for rebiopsy upon progression after an egfr tki, rebiopsy methods and complications, number of rebiopsies, and incidence of the T790M mutation were collected. Results:Of 84 patients considered for trial enrolment, 80 signed a consent. In 78 patients who underwent rebiopsy, computed tomography or ultrasonography guidance were the most common methods used. The most common biopsy sites were lung and lymph nodes. The median number of rebiopsies performed to find a T790M mutation was 2. Only 9% of patients experienced complications. Of samples obtained, 74% were adequate for testing after initial rebiopsy. A T790M mutation was found in 47 patients, of whom 44 were enrolled on a trial. After multiple rebiopsies, only 5% of samples were inadequate for molecular analysis. Conclusions:In the Canadian setting, the acceptance of rebiopsy on progression was high. Multiple rebiopsies were clinically feasible and could increase the yield for T790M mutation. The incidence of complications was low despite the most common site for rebiopsy being lung.

SUBMITTER: Chu Q

PROVIDER: S-EPMC7096193 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Biopsy on progression in patients with <i>EGFR</i> mutation-positive advanced non-small-cell lung cancer-a Canadian experience.

Chu Q Q Agha A A Devost N N Walton R N RN Ghosh S S Ho C C

Current oncology (Toronto, Ont.) 20200201 1

<h4>Background</h4>Epidermal growth factor receptor (egfr) tyrosine kinase inhibitors (tkis) are standard therapy for patients with advanced or metastatic non-small-cell lung cancer harbouring an <i>EGFR</i> mutation. Upon progression, 50%-60% develop a secondary T790M mutation. Recent trials demonstrated outcome improvement with osimertinib compared with standard platinum-based chemotherapy as second-line therapy for patients with secondary T790M mutation. To identify T790M, a biopsy of the tum ...[more]

PMID: 32218657

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Project description:BackgroundEGFR-positive Non-small Cell Lung Cancer (NSCLC) is a dynamic entity and tumor progression and resistance to tyrosine kinase inhibitors (TKIs) arise from the accumulation, over time and across different disease sites, of subclonal genetic mutations. For instance, the occurrence of EGFR T790M is associated with resistance to gefitinib, erlotinib, and afatinib, while EGFR C797S causes osimertinib to lose activity. Sensitive technologies as radiomics and liquid biopsy have great potential to monitor tumor heterogeneity since they are both minimally invasive, easy to perform, and can be repeated over patient's follow-up, enabling the extraction of valuable information. Yet, to date, there are no reported cases associating liquid biopsy and radiomics during treatment.Case presentationIn this case series, seven patients with metastatic EGFR-positive NSCLC have been monitored during target therapy. Plasma-derived cell free DNA (cfDNA) was analyzed by a digital droplet PCR (ddPCR), while radiomic analyses were performed using the validated LifeX® software on computed tomography (CT)-images. The dynamics of EGFR mutations in cfDNA was compared with that of radiomic features. Then, for each EGFR mutation, a radiomic signature was defines as the sum of the most predictive features, weighted by their corresponding regression coefficients for the least absolute shrinkage and selection operator (LASSO) model. The receiver operating characteristic (ROC) curves were computed to estimate their diagnostic performance. The signatures achieved promising performance on predicting the presence of EGFR mutations (R2 = 0.447, p <0.001 EGFR activating mutations R2 = 0.301, p = 0.003 for T790M; and R2 = 0.354, p = 0.001 for activating plus resistance mutations), confirmed by ROC analysis.ConclusionTo our knowledge, these are the first cases to highlight a potentially promising strategy to detect clonal heterogeneity and ultimately identify patients at risk of progression during treatment. Together, radiomics and liquid biopsy could detect the appearance of new mutations and therefore suggest new therapeutic management.

Dataset Information

Biopsy on progression in patients with EGFR mutation-positive advanced non-small-cell lung cancer-a Canadian experience.

Publications

Biopsy on progression in patients with <i>EGFR</i> mutation-positive advanced non-small-cell lung cancer-a Canadian experience.

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