4084 Background: Treatment of advanced CCA has changed dramatically over the past five years with the advent of molecularly targeted therapy, now approved in the 2nd line and beyond. However, real world utilization of molecular profiling and targeted therapy is still unknown and these data are critical to empower treatment decision-making. Methods: In 2019, the Cholangiocarcinoma Foundation (CCF) and Ciitizen (a wholly owned subsidiary of Invitae Corporation) collaboratively launched a registry platform that directly consents patients and collects comprehensive medical records. De-identified data including clinical characteristics, molecular testing, interventions, and outcomes are extracted and standardized for research use. The data is longitudinal with regularly planned updates; registry participants can be re-engaged to obtain additional data and communicate tailored insights. Results: We quantified the rate of molecular testing, the presence of targetable biomarkers, and the utilization and outcomes on matched targeted therapies for 372 individuals with CCA. 328 (88.2%) individuals had molecular testing, with the identified targetable mutations and matched therapies reported. Of 328 individuals who had molecular testing, 111 (33.8%) individuals had one or more targetable mutations (116 mutations total). Only 46% (51) of individuals with targetable mutations received targeted therapy. Of the 54% (60) individuals with targetable mutations that did not receive any matched therapy, the majority (61.7%, 37) were in early disease or first line of treatment and therefore not yet eligible for targeted therapy. These individuals will be informed that based on their molecular profile, a targeted therapy may be an option, and suggest they discuss with their treating physician. Conclusions: A novel prospectively-maintained database registry for CCA has been formed in collaboration between a patient advocacy organization (CCF) and industry (Invitae). Prevalence of actionable biomarkers was higher than historically expected and may reflect patient utilization bias of the registry platform. Molecular profiling and access to targeted therapeutics remains suboptimal at this time in CCA. Future directions for the registry include identifying and targeting disparities in care and supporting biopharmaceutical development and regulatory decisions. [Table: see text]
Objective: To validate and demonstrate the clinical discovery utility of a novel patient-mediated, medical record collection and data extraction platform developed to improve access and utilization of real-world clinical data. Methods: Clinical variables were extracted from the medical records of consented patients with metastatic breast cancer. To validate the extracted data, case report forms completed using the structured data output of the platform were compared to manual chart review for 50 patients. To demonstrate the platform's clinical discovery utility, we assessed associations between time to distant metastasis (TDM) and tumor histology, molecular type, and germline BRCA status in the platform-extracted data of 194 patients. Results: The platform-extracted data had 97.6% precision (91.98%-100% by variable type) and 81.48% recall (58.15%-95.00% by variable type) compared to manual chart review. In our discovery cohort, the shortest TDM was significantly associated with metaplastic (739.0 days) and inflammatory histologies (1,005.8 days), HR-/HER2- molecular types (1,187.4 days), and positive BRCA status (1,042.5 days) as compared to other histologies, molecular types, and negative BRCA status, respectively. Multivariable analyses did not produce statistically significant results, but the average TDMs are reported. Discussion: The platform-extracted clinical data are precise and comprehensive. The data can generate clinically-relevant insights. Conclusion: The structured real-world data produced by a patient-mediated, medical record-extraction platform are reliable and can power clinical discovery. Keywords: data accuracy; electronic health records; real-world data; real-world evidence
Introduction: Currently, the NCCN guidelines for invasive breast cancer (BC) surveillance are the same regardless of tumor pathology. The length of time between initial diagnosis and documented distant metastasis based on tumor subtypes has not been well-studied in real-world settings, which means that for any given patient, generalized screening recommendations may be either too stringent or too relaxed. Here, we report how tumor histologic and molecular characteristics analyzed from a real-world data platform correlate with the average time to distant recurrence. This information can guide more personalized surveillance for BC patients. Methods: Ciitizen (a wholly owned subsidiary of Invitae) leverages HIPAA right of access on behalf of patients to collect their medical records, extracts relevant clinical information into a standardized and validated longitudinal dataset, and - with their consent - enables research use of this data. From our current invasive BC cohort (n=1011), we identified a subcohort who were diagnosed at Stage I-III with associated histology and/or molecular characterization, then ultimately went on to develop distant metastases (n=195 cases involving 321 sites: bone, brain, liver, and/or lung). We calculated time from initial diagnosis to confirmation of distant metastasis at each site, and statistically analyzed differences using pooled hypothesis testing. Results: In addition to finding expected associations between molecular type and site(s) of metastasis, i.e. bone and brain more common in Hormone Receptor Positive (HR+) subtypes vs HR-, we also characterized the average time to distant metastasis (TDM) to identify other statistically significant associations: Molecular Type: HR-/HER2- (n=30) has an average TDM of 1124 days, which is significantly faster than HR+/HER2- (2224 days; n=197) and HR+/HER2+ (2159 days; n=32) (p=0.0043). BRCA: Individuals with BRCA1/2 pathogenic germline variants have an average TDM of 1043 days (n=15), significantly earlier than individuals with normal BRCA1/2 (2238 days; n=179) (p <0.0001). Histology: Ductal carcinomas have an average TDM of 2262 days (n=242) and lobular carcinomas have an average TDM of 2812 days (n=24), both of which are significantly longer than the rarer metaplastic (739 days; n=11) and inflammatory (978 days; n=5) (p=0.0001). Conclusions: These real-world findings characterize average time to metastasis and reveal statistically significant associations based on histologic and molecular type, which taken together can inform more personalized screening recommendations for BC patients. Since the Ciitizen data platform also includes additional treatment and outcome variables, future studies can explore the relationships between these various features towards more granular prognostic and predictive classifications. Citation Format: Amanda Nottke, Anthony B. Cardillo, Hana E. Littleford, Lisandra West-Odell, Alexandra Berk. A novel real world clinico-genomics data platform identifies breast cancer histologic and molecular characteristics as candidate predictors for time to distant metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4088.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.