Combined Focused Next-Generation Sequencing Assays to Guide Precision Oncology in Solid Tumors: A Retrospective Analysis from an Institutional Molecular Tumor Board

• Published in: Cancers Vol. 14; no. 18; p. 4430
• Main Authors: Tarawneh, Thomas S., Rodepeter, Fiona R., Teply-Szymanski, Julia, Ross, Petra, Koch, Vera, Thölken, Clemens, Schäfer, Jonas A., Gremke, Niklas, Mack, Hildegard I. D., Gold, Judith, Riera-Knorrenschild, Jorge, Wilhelm, Christian, Rinke, Anja, Middeke, Martin, Klemmer, Andreas, Romey, Marcel, Hattesohl, Akira, Jesinghaus, Moritz, Görg, Christian, Figiel, Jens, Chung, Ho-Ryun, Wündisch, Thomas, Neubauer, Andreas, Denkert, Carsten, Mack, Elisabeth K. M.
• Format: Journal Article
• Language: English
• Published: Basel MDPI AG 01.09.2022; MDPI
• Subjects: Biochemical assays; Biomarkers; Cancer therapies; Care and treatment; Consortia; FDA approval; Gene fusion; gene panels; Genes; Genomes; Immunohistochemistry; Interdisciplinary aspects; Leukemia; Medical prognosis; Medical research; Methods; Microsatellite instability; molecular tumor board; Mutation; Next-generation sequencing; Oncology; Patients; PD-L1 protein; Precision medicine; precision oncology; Solid tumors; Therapeutic targets; Tumors; ultra-low-coverage whole-genome sequencing; Whole genome sequencing; Germany; United States > US
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers14184430

Background: Increasing knowledge of cancer biology and an expanding spectrum of molecularly targeted therapies provide the basis for precision oncology. Despite extensive gene diagnostics, previous reports indicate that less than 10% of patients benefit from this concept. Methods: We retrospectively analyzed all patients referred to our center’s Molecular Tumor Board (MTB) from 2018 to 2021. Molecular testing by next-generation sequencing (NGS) included a 67-gene panel for the detection of short-sequence variants and copy-number alterations, a 53- or 137-gene fusion panel and an ultra-low-coverage whole-genome sequencing for the detection of additional copy-number alterations outside the panel’s target regions. Immunohistochemistry for microsatellite instability and PD-L1 expression complemented NGS. Results: A total of 109 patients were referred to the MTB. In all, 78 patients received therapeutic proposals (70 based on NGS) and 33 were treated accordingly. Evaluable patients treated with MTB-recommended therapy (n = 30) had significantly longer progression-free survival than patients treated with other therapies (n = 17) (4.3 vs. 1.9 months, p = 0.0094). Seven patients treated with off-label regimens experienced major clinical benefits. Conclusion: The combined focused sequencing assays detected targetable alterations in the majority of patients. Patient benefits appeared to lie in the same range as with large-scale sequencing approaches.