Biomarker data are critical to the delivery of precision cancer care. The average turnaround of next-generation sequencing (NGS) reports is over 2 weeks, and in-house availability is typically limited to academic centers. Lengthy turnaround times for biomarkers can adversely affect outcomes. Traditional workflows involve moving specimens through multiple facilities. This study evaluates the feasibility of rapid comprehensive NGS using the Genexus integrated sequencer and a novel streamlined workflow in a community setting. Methods: A retrospective chart review was performed to assess the early experience and performance characteristics of a novel approach to biomarker testing at a large community center. This approach to NGS included an automated workflow utilizing the Genexus integrated sequencer, validated for clinical use. NGS testing was further integrated within a routine immunohistochemistry (IHC) service, utilizing histotechnologists to perform technical aspects of NGS, with results reported directly by anatomic pathologists. Results: Between October 2020 and October 2021, 578 solid tumor samples underwent genomic profiling. Median turnaround time for biomarker results was 3 business days (IQR: 2–5). Four hundred eighty-one (83%) of the cases were resulted in fewer than 5 business days, and 66 (11%) of the cases were resulted simultaneously with diagnosis. Tumor types included lung cancer (310), melanoma (97), and colorectal carcinoma (68), among others. NGS testing detected key driver alterations at expected prevalence rates: lung EGFR (16%), ALK (3%), RET (1%), melanoma BRAF (43%), colorectal RAS/RAF (67%), among others. Conclusion: This is the first study demonstrating clinical implementation of rapid NGS. This supports the feasibility of automated comprehensive NGS performed and interpreted in parallel with diagnostic histopathology and immunohistochemistry. This novel approach to biomarker testing offers considerable advantages to clinical cancer care.

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Introduction Cancer of unknown primary remains a challenging clinical entity. Despite receiving empiric chemotherapy, median overall survival is approximately 6-12 months. Site-specific therapy based on molecular characterization has been shown to improve outcomes; however, feasibility outside of clinical trials, especially in community centers, is lacking. This study explores the application of rapid next-generation sequencing in defining cancer of unknown primary and to identify therapeutic biomarkers. Methods A retrospective chart review was performed by identifying pathological samples designated cancer of unknown primary. Next-generation sequencing testing was based on an automated workflow utilizing the Genexus integrated sequencer, validated for clinical use. Genomic profiling was further integrated within a routine immunohistochemistry service, with results reported directly by anatomic pathologists. Results Between October 2020 and October 2021, 578 solid tumor samples underwent genomic profiling. Among this cohort, 40 were selected based on an initial diagnosis of cancer of unknown primary. The median (range) age at diagnosis was 70 (42-85) and 23 (57%) were female. Genomic data were used to support a site-specific diagnosis in 6 patients (15%). Median turnaround time was 3 business days (IQR: 1-5). Most common alterations identified were KRAS (35%), CDKN2A (15%), TP53 (15%), and ERBB2 (12%). Actionable molecular targeted therapies were identified in 23 (57%) patients, including alterations in BRAF, CDKN2A, ERBB2, FGFR2, IDH1, and KRAS. Immunotherapy-sensitizing mismatch repair deficiency was identified in 1 patient. Conclusion This study supports the adoption of rapid next-generation sequencing among patients with cancer of unknown primary. We also demonstrate the feasibility of integration of genomic profiling with diagnostic histopathology and immunohistochemistry in a community practice setting. Diagnostic algorithms incorporating genomic profiling to better define cancer of unknown primary should be considered for future study.

3143 Background: Biomarker data in the form of next generation sequencing (NGS) are critical to the delivery of precision cancer care. Onsite testing is often limited to large academic centers, requiring smaller community centers to rely on samples send outs. Turnaround time for biomarkers can be lengthy and can adversely affect the delivery of optimal therapy in many tumor types. This study aims to evaluate the feasibility of rapidly delivered comprehensive NGS in a community center using a novel workflow in the laboratory by integrating NGS into the routine immunohistochemistry (IHC) service. Methods: An automated NGS workflow utilizing the Genexus integrated sequencer with the Oncomine precision assay GX (OPA, Thermofisher Scientific), was validated for clinical use and integrated into the routine diagnostic IHC service. During the study period (Oct 2020 – Oct 2021), NGS biomarker data was generated and reported alongside IHC biomarkers where applicable. A retrospective chart review was performed to assess the early experience and performance characteristics of this novel approach to biomarker testing. Results: A total of 578 solid tumor samples underwent genomic profiling. Median turnaround time for biomarker results was 3 business days (IQR 2-5). The majority (n = 481, 83%) of cases were resulted in fewer than 5 business days. Tumor types included lung cancer (n = 310, 54%), melanoma (n = 97, 17%), and colorectal cancer (n = 68, 12%). Specimen types included surgical resections (n = 104, 18%), core biopsies (n = 411, 71%), and cytology specimens (n = 63, 11%). NGS testing detected key driver alterations at expected prevalence rates in respective tumor types; lung EGFR (16%), ALK (3%), RET (1%), melanoma BRAF (43%), colorectal RAS/RAFwild-type (33%), among others. Conclusions: This is the first study demonstrating the clinical feasibility and turnaround time statistics of automated comprehensive NGS performed and interpreted in parallel with diagnostic histopathology and immunohistochemistry in a community setting. This novel approach of integrating biomarkers, IHC, and morphology offers rapid turnaround by removing the need for outsourcing biomarker data. This model could be adopted by other community centers to improve rapid access to biomarker data and therapeutic decision making.