Abstract 953: Integration of functional precision medicine assay for high grade glioma management: A single institution experience
Authors: Guzman Grace , Bettadapura Sahana , Shelton-Correa William Jeremy , Brooks Taylor , Rayner Melissa , Wardell Christopher , Rodriguez Analiz 
Published: March 2024

Despite the advances in precision oncology, genomic approaches have not significantly improved outcomes for high grade gliomas (HGGs) as once was anticipated. Recurrent HGG pose even greater therapeutic challenge. The integration of functional precision medicine (FPM), in which drugs screens are performed on live tissue, into clinical routine practice presents a promising alternative by offering personalized treatments based on the unique characteristics of the patient’s tumor. Here, we present our institutional experience of integrating a spheroid-based drug screening assay (3D PredictTM Glioma) in the treatment management of HGG patients to evaluate its feasibility and efficacy as a therapeutic tool in a clinical setting. We also sought to determine factors that related to assay success. Tissue from intracranial lesions of patients with presumed HGG and planned surgical resection at our institution were collected for ex vivo 3D cell culture and challenged with 12 drug agents to determine patient-specific response parameters. The impact of potential variables, such as ki67, tumor pathology, and shipment timing, on the assay’s success was evaluated. Clinical correlation was established between ex vivo response and clinical response in HGG patients. 57 samples, including 24 upfront HGGs, 32 recurrent HGGs, and one medulloblastoma, were sent for spheroid formation and drug testing. In total, 57.9% (33/57) or 23% (13/57) of the assays were successful and resulted in complete or partial functional profiling data, respectively. We conducted a multivariable analysis of our cohort to determine which variables (i.e. tumor volume sent, ki-67 proliferation index, tumor percentage determined by DNA sequencing by Tempus Lab, recurrent status, sample shipment time) were predictive of assay success. The only variable significantly associated with assay success was tumor percentage with samples comprised of &gt;70% tumor leading to assay success, 40%-70% leading to 60% chance of success, and &lt;40% having 0% success. Among 46 patients with partial or complete assay success, 26 patients (56.5%) had a targetable mutation and 17/26 yielded a moderate or full response to one or more of their corresponding targeted drugs in the assay. Treatments were newly administered or altered from prior treatments in 40/57 patients (70%) based on FPM results. Our study demonstrates the technical feasibility of incorporating FPM approaches in the development of treatment regimens for patients with HGG. Success was correlated to tumor percentage present in the sample which indicates intraoperative communication between surgeon and pathologist can lead to improved assay results. Our institutional protocol demonstrates that Integrating FPM into routine clinical practice is possible and can serve as a valuable guide in the refinement of therapeutic recommendations for HGG patients.

Citation Format: Grace Guzman, Sahana Bettadapura, William Jeremy Shelton-Correa, Taylor Brooks, Melissa Rayner, Christopher Wardell, Analiz Rodriguez. Integration of functional precision medicine assay for high grade glioma management: A single institution experience [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 953.