Libros for Oregon: Collections Connect Communities A New LSTA Grant to Help More Oregon Libraries Take Advantage of the Guadalajara Book Fair

Acquiring good books in Spanish for our libraries is a perennial challenge. In the fall of 2015, a discussion arose on some Oregon library listservs about the challenge of connecting our patrons with culturally-appropriate, high-quality Spanish books. Author Gitlitz gathered a team to put together an LSTA grant proposal for a project called “Libros for Oregon,” with a goal of increasing access to high-quality Spanish language books for the users of Oregon libraries, particularly smaller, rural libraries. The project has three parts: (1) form an Oregon library book-buying cooperative (with new participants each year) to purchase materials for members at the International Book Fair (FIL) in Guadalajara; (2) help participating libraries to develop and implement outreach plans for connecting their enhanced collections with their Hispanic/Latino communities; and (3) create a “Best of FIL” booklist (annotated to show US availability) for all Oregon libraries to use in collection development. The article explains the grant’s goals and timeline; gives a sense of the immense Guadalajara book fair; and discusses avenues for Oregon libraries to participate in this project in upcoming years. This project is supported in part by the Institute of Museum and Library Services through the Library Services and Technology Act, administered by the Oregon State Library. Este programa es patrocinado en parte por el Instituto de Museo y Servicios Bibliotecarios a través de la Ley de Servicios Bibliotecarios y Tecnológicos (LSTA), administrado por la Biblioteca Estatal de Oregón

Abstract A1-36: The genomics of young lung cancer

Abstract Primary lung cancer is increasingly understood as a heterogeneous disease made up of genomically defined subtypes requiring distinct treatment strategies. We hypothesize young age at diagnosis (&amp;lt;40 years) is a clinical characteristic associated with an increased chance for a targetable mutation. Our study will prospectively characterize the somatic and germline genomics of young lung cancer (GYLC). Our goals are to identify a genomically enriched subtype of lung cancer, facilitate delivery of targeted therapy and lay the groundwork for further studies of heritable and environmental lung cancer risk factors. A website allows for virtual consenting so patients can participate remotely and use social media to share our trial. We have defined 7 genomic alterations of interest, based on the lung cancer mutational consortium (LCMC) (EGFR, KRAS, HER2, BRAF, ALK, ROS1, RET). Subjects will undergo CLIA genomics to ensure that all of these genes have been tested. Those who are wild type will receive additional CLIA genomics using the FoundationOne® Heme panel, with the goal of identifying novel oncogenic drivers. Additional investigational genomics will include blood for germline testing. We believe the prevalence of targetable mutations will be greater in our population as compared to the LCMC and have powered our study to show an increase from 35% to 50%; and an improvement in the use of targeted therapy from 22% to 40%. The trial is currently accruing (NCT02273336). Preliminary results at 20% accrual show over 60% of pts with ALK, ROS1 or EGFR mutations. Further results to be presented at the meeting. (This trial is facilitated by the Addario Lung Cancer Medical Institute) Citation Format: Barbara J. Gitlitz, Deborah Morosini, Alicia Sable-Hunt, Bonnie J. Addario, Geoffrey R. Oxnard. The genomics of young lung cancer. [abstract]. In: Proceedings of the AACR Special Conference on Translation of the Cancer Genome; Feb 7-9, 2015; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2015;75(22 Suppl 1):Abstract nr A1-36.</jats:p

Molecular determinants of outcome for metastatic castration-sensitive prostate cancer (mCSPC) with addition of apalutamide (APA) or placebo (PBO) to androgen deprivation therapy (ADT) in TITAN.

5535 Background: In TITAN, addition of APA to ADT improved radiographic progression-free survival (rPFS) and overall survival (OS) versus PBO plus ADT in patients (pts) with mCSPC. In this post hoc analysis, we performed transcriptome-wide profiling of tumor samples and assessed association of molecular subtypes with rPFS. Methods: The DECIPHER platform (Decipher Biosciences, Inc.) was used to assess gene expression in archival primary prostate tumors from TITAN. Samples were classified into high versus low to average risk of metastases (DECIPHER genomic classifier [GC] &gt; 0.6 and ≤ 0.6, respectively), basal and luminal A/B (PAM50 classifier), and androgen receptor activity (AR-A) signature high and low. Associations between subtypes with rPFS were assessed with Cox proportional hazards model. Results: The biomarker population included 222 pts (APA, 110; PBO, 112). Benefit in rPFS from APA in the biomarker population (HR [95% CI]; p value; 0.49 [0.31-0.78]; 0.002) resembled that in the overall study population (0.49 [0.40-0.61]; &lt; 0.0001). The majority of TITAN pts had GC high scores (n = 166, 75%). GC high risk subtype in the PBO group had poorer prognosis for rPFS than GC low to average risk subtype (median rPFS 18.2 mos for GC high vs not reached [NR] for GC low to average, 0.28 [0.11-0.69]; 0.006), but there was no difference in prognosis between high and low to average GC risk subtypes in the APA group (GC high NR vs GC low to average NR; 0.81 [0.35-1.89]; 0.625). Pts were further stratified based on basal/luminal and AR-A signatures. Basal (n = 112, 50%) and AR-A low (n = 96, 43%) subtypes, known to be nonresponsive to ADT, both showed significant benefit from APA vs PBO (0.30 [0.16-0.57]; &lt; 0.001 and 0.25 [0.12-0.52]; &lt; 0.001, respectively). The majority of AR-A low subtype (74%, 71/96) overlapped with basal subtype. Further conclusions for risk of rPFS in GC low, luminal, and AR-A high subtypes and OS across all subtypes will be assessed as more events occur. Conclusions: In TITAN, addition of APA to ADT improved rPFS for all subtypes of pts with mCSPC. APA overcame the poor prognosis of GC high risk subtype and prolonged rPFS in ADT-resistant AR-A low and basal molecular subtypes, suggesting APA is beneficial especially for the highest risk molecular subtypes. Clinical trial information: NCT02489318 . </jats:p

Blood Biomarker Landscape in Patients with High-risk Nonmetastatic Castration-Resistant Prostate Cancer Treated with Apalutamide and Androgen-Deprivation Therapy as They Progress to Metastatic Disease

Abstract Purpose: In the placebo-controlled SPARTAN study, apalutamide added to androgen-deprivation therapy (ADT) improved metastasis-free survival, second progression-free survival (PFS2), and overall survival (OS) in patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). Mechanisms of resistance to apalutamide in nmCRPC require evaluation. Patients and Methods: In a subset of patients from SPARTAN, aberrations were assessed at baseline and end of study treatment (EOST) using targeted next-generation sequencing or qRT-PCR. Circulating-tumor DNA (ctDNA) levels were assessed qualitatively. Select aberrations in androgen receptor (AR) and other common PC-driving genes were detected and summarized by the treatment group; genomic aberrations were summarized in ctDNA-positive samples. Association between detection of aberrations in all patients and outcomes was assessed using Cox proportional-hazards models and multivariate analysis. Results: In 247 patients, the overall prevalence of ctDNA, AR aberrations, and TP53 inactivation increased from baseline (40.6%, 13.6%, and 22.2%) to EOST (57.1%, 25.4%, and 35.0%) and was comparable between treatment groups at EOST. In patients who received subsequent androgen signaling inhibition after study treatment, detectable biomarkers at EOST were significantly associated with poor outcomes: ctDNA with PFS2 or OS (HR, 2.01 or 2.17, respectively; P &amp;lt; 0.0001 for both), any AR aberration with PFS2 (1.74; P = 0.024), and TP53 or BRCA2 inactivation with OS (2.06; P = 0.003; or 3.1; P &amp;lt; 0.0001). Conclusions: Apalutamide plus ADT did not increase detectable AR/non-AR aberrations over ADT alone. Detectable ctDNA, AR aberrations, and TP53/BRCA2 inactivation at EOST were associated with poor outcomes in patients treated with first subsequent androgen signaling inhibitor. </jats:sec