Potential utility of <i>FGFR2</i> mutation status as an adverse prognostic factor to affect clinical decision-making.

<p>The decision tree is adapted from 2011 National Comprehensive Cancer Network guidelines using FIGO 2009 staging. BT = brachytherapy; RT = radiation therapy.</p

Schematic figure of FGFR2 mutations identified in endometrioid endometrial tumors.

<p>Blue diamonds indicate each instance of a mutation in the Washington University School of Medicine cohort. Mutations are numbered relative to <i>FGFR2</i>b (NP_075259.2). Mutations at 6 codons (S252, P253, Y376, C383, N550, K660) comprise >90% of all mutations identified.</p

Hazard Ratio (HR) and 95% Confidence Interval (CI) for Cohort of 466 Endometrioid Endometrial Cancers.

<p>*For DFS, the multivariate model included Stage 1C, II, III/IV, grade 2 and 3.</p><p>**For OS, the multivariate model included age, FIGO stage 1C, II, III/IV, grade 2 and grade 3.</p>a<p>FGFR2 adjusted for KRAS in addition to covariates above.</p>b<p>KRAS adjusted for FGFR2 in addition to covariates above.</p

Patient Demographics and Clinicopathologic Characteristics.

<p>Patient Demographics and Clinicopathologic Characteristics.</p

Hazard ratio (HR) and 95% confidence interval (CI) for cohort of 386 Stage I/II cases.

<p>*For DFS, the multivariate model included Stage 1C, II, Grade 2 and 3.</p><p>**For OS, the multivariate model included age, FIGO Stage 1C, II, Grade 2 and Grade 3.</p>a<p>FGFR2 adjusted for KRAS in addition to covariates above.</p>b<p>KRAS adjusted for FGFR2 in addition to covariates above.</p

A prospective pilot study of genome-wide exome and transcriptome profiling in patients with small cell lung cancer progressing after first-line therapy

<div><p>Background</p><p>Small cell lung cancer (SCLC) that has progressed after first-line therapy is an aggressive disease with few effective therapeutic strategies. In this prospective study, we employed next-generation sequencing (NGS) to identify therapeutically actionable alterations to guide treatment for advanced SCLC patients.</p><p>Methods</p><p>Twelve patients with SCLC were enrolled after failing platinum-based chemotherapy. Following informed consent, genome-wide exome and RNA-sequencing was performed in a CLIA-certified, CAP-accredited environment. Actionable targets were identified and therapeutic recommendations made from a pharmacopeia of FDA-approved drugs. Clinical response to genomically-guided treatment was evaluated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1.</p><p>Results</p><p>The study completed its accrual goal of 12 evaluable patients. The minimum tumor content for successful NGS was 20%, with a median turnaround time from sample collection to genomics-based treatment recommendation of 27 days. At least two clinically actionable targets were identified in each patient, and six patients (50%) received treatment identified by NGS. Two had partial responses by RECIST 1.1 on a clinical trial involving a PD-1 inhibitor + irinotecan (indicated by <i>MLH1</i> alteration). The remaining patients had clinical deterioration before NGS recommended therapy could be initiated.</p><p>Conclusions</p><p>Comprehensive genomic profiling using NGS identified clinically-actionable alterations in SCLC patients who progressed on initial therapy. Recommended PD-1 therapy generated partial responses in two patients. Earlier access to NGS guided therapy, along with improved understanding of those SCLC patients likely to respond to immune-based therapies, should help to extend survival in these cases with poor outcomes.</p></div

NGS turnaround time metrics.

<p>NGS turnaround time metrics.</p

CONSORT diagram.

<p>Displays the flow of the 13 patients who consented and were evaluated for the study. There was one screen failure due to anticipated inadequate sample yield because of tumor location.</p

Clinical characteristics for the eligible patients.

<p>Clinical characteristics for the eligible patients.</p

NGS sequencing metrics.

<p>NGS sequencing metrics.</p