Utility Of Clinical Sequencing Research Articles

Abstract 6456: The utility of clinical sequencing in the diagnosis and treatment of soft tissue sarcomas; Real world data based on nation-wide database

Abstract Purpose: Soft tissue sarcomas (STS) are rare and heterogeneous tumors arising from mesenchymal connective tissue, accounting for approximately 1%-2% of all malignancies. Due to their rarity and heterogeneity, it is challenging for accurate diagnosis, prognosis, and treatment of sarcoma. Recently, next-generation sequencing (NGS)-based comprehensive cancer genome profiling (CGP) has increasingly become a routine practice for patients with solid cancers worldwide. To collect genomic information and clinical characteristics of patients who underwent CGP, the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) has also been established since 2018 in Japan. Almost all the clinical and genomic data of patients who received CGP tests the had been collected in C-CAT. Here, we examined the utility of CGP test in the diagnosis and treatment of STS using this nation-wide database. Patients and Methods: We retrospectively evaluated the records of patients with STS who received F1CDx between 2019 and 2022 and registered in C-CAT. This assay carries 324 genes and determines nucleotide substitutions, insertions/deletions, and copy number (CN) alterations of 309 genes, fusions of 36 genes, tumor mutation burden (TMB) and microsatellite instability (MSI). High TMB (TMB-H) was defined as a TMB value >10 muts/Mb. Ranges of the MSI score were assigned MSI-High (MSI-H) or microsatellite stable (MSS). Results: From 2019 to 2022, 1387 patients with STS were registered in C-CAT. The histological types included leiomyosarcoma in 357 patients, dedifferentiated liposarcoma in 178 patients, and undifferentiated pleomorphic sarcoma in 82 patients, and the others. The most commonly altered genes included TP53, CDKN2A, Rb1, and CDKN2B. Among the 1387 cases, we observed 110 fusion events in 108 cases (7.7%), and 2 cases showed 2 types of fusion transcripts. Fifteen (2.8%) patients were re-classified based on the detection of highly histology-specific translocations. Among them, an initial diagnosis of sarcoma NOS was classified as Ewing Sarcoma (EWSR1-FLI1 in 2 patients), NTRK-rearranged spindle cell neoplasm (NTRK fusion in 3 patients), CIC-rearranged sarcoma (CIC-DUX4 in 3 patients), and sarcoma with BCOR genetic alterations (BCOR-ZC3H7B in 1 patient) as these gene fusions were identified. Druggable gene alterations was detected in 347 patients (25%) and 55 patients (4%) who received genotype-matched therapy. In 38 patients for whom the effect of treatment could be evaluated, complete response and partial response were achieved in 2 (5%) and 10 (26%) patients, respectively. Discussion: In conclusion, the comprehensive genomic profiling test appears to be an important tool in the diagnosis and treatment of sarcomas. Citation Format: Eiji Nakada, Tomohiro Fujiwara, Toshi Kunisada, Shota Takihira, Daisuke Ennishi, Hideki Yamamoto, Kiichiro Ninomiya, Shuta Tomida, Mashu Futagawa, Akira Hirasawa, Shinichi Toyooka, Toshifumi Ozaki. The utility of clinical sequencing in the diagnosis and treatment of soft tissue sarcomas; Real world data based on nation-wide database [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 6456.

Utility of circulating tumor DNA (ctDNA) versus tumor tissue clinical sequencing for enrolling patients (Pts) with advanced gastrointestinal (GI) cancer to matched clinical trials: SCRUM-Japan GI-SCREEN and GOZILA Combined Analysis.

5 Background: Blood-based genomic profiling by ctDNA analysis has a promise to potentially identify actionable genomic alterations. However, utility of clinical sequencing with ctDNA compared with that with tumor tissue for enrolling cancer pts to matched clinical trials remains unclear. Herein we investigated the utility of ctDNA clinical sequencing by the SCRUM-Japan GI-SCREEN and GOZILA Combined Analysis. Methods: In the GI-SCREEN, tumor tissue samples of pts with advanced GI cancer were analyzed by a next generation sequencing (NGS)-based assay, Oncomine Comprehensive Assay since Feb 2015. In the GOZILA, plasma samples of pts with advanced GI cancer were analyzed by an NGS-based ctDNA assay, Guardant360 since Feb 2018. Tests were performed centrally by CLIA-certified and CAP-accredited laboratories. Pts with actionable alterations were enrolled to matched company-sponsored or investigator-initiated clinical trials. Results: As of Apr 2019, test results were generated in 5,029 out of 5,743 pts (88%) in GI-SCREEN and 1,089 out of 1,103 pts (99%) in GOZILA ( P < 0.0001).Median turnaround time (TAT) was 35 days in GI-SCREEN and 12 days in GOZILA ( P < 0.0001). There were no differences in other baseline characteristics between GI-SCREEN and GOZILA. Proportion of enrolling matched clinical trials in GOZILA was significantly higher than that in GI-SCREEN (126 pts [2.2%] in GI-SCREEN vs. 60 pts [5.4%] in GOZILA, P < 0.0001). Median time from GI-SCREEN or GOZILA enrollment to clinical trial enrollment was 5.9 and 1.0 months (mo), respectively ( P < 0.0001). The objective response rate (ORR) and progression-free survival (PFS) were not significantly different (ORR: 17.5 vs. 16.7%, P = 1.00; median PFS: 2.8 vs. 2.0 mo, P = 0.24). Conclusions: Clinical sequencing with ctDNA having the advantage of the shorter TAT enrolled more pts with advanced GI cancer to matched clinical trials than those with tumor tissue, without compromising the efficacy. Clinical trial information: UMIN000029315.

Assessing real-world outcomes in precision oncology by linking clinical genomic testing to electronic medical records.

e18091 Background: With an ever-widening array of targeted therapies for cancer patients, clinical genomic testing has expanded rapidly in recent years. Tumor molecular profiling by next-generation sequencing is now considered a cornerstone of precision oncology, with the potential to offer patients with advanced cancers new therapeutic options. However, the overall impact of this testing remains unclear, and evidence demonstrating improvement in patient outcomes is lacking. The objective of this study is to assess the utility of clinical sequencing on the management of cancer patients. Methods: We present the development of a database that combines results of tumor mutation profiling using various next-generation sequencing panels (both external commercial tests and our institution’s internal sequencing panel), with a variety of data points from a de-identified representation of our institution’s electronic medical record (EMR). Assembling this data from different sources into a common relational database permits efficient retrospective analysis of real-world outcomes in patients with advanced cancers. Results: This study included over 3000 patients seen at UCSF Comprehensive Cancer Center since 2013. With this linked data set we analyzed the rate at which tumor molecular profiling affected clinical decision making, identified barriers to the efficient use of testing, and assessed for disparities in utilization. For example, by measuring patient survival relative to the clinical intervention of genomic testing for the subset of patients with a date of death recorded in our EMR, we found that a small fraction of patients died before results returned and any action could be taken, especially in cases of pancreatic cancer. Conclusions: We demonstrate that a common relational database combining clinical sequencing results with real-world EMR data provides insights into the optimal clinical use of tumor molecular profiling. This provides new opportunities for advancing precision oncology initiatives and improving patient care, such as identifying which cancer patients should get genomic testing and efficiently matching patients to clinical trials.