Feasibility of multiomics tumor profiling for guiding treatment of melanoma

IF 58.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Nicola Miglino, Nora C. Toussaint, Alexander Ring, Ximena Bonilla, Marina Tusup, Benedict Gosztonyi, Tarun Mehra, Gabriele Gut, Francis Jacob, Stephane Chevrier, Kjong-Van Lehmann, Ruben Casanova, Andrea Jacobs, Sujana Sivapatham, Laura Boos, Parisa Rahimzadeh, Manuel Schuerch, Bettina Sobottka, Natalia Chicherova, Shuqing Yu, Rebekka Wegmann, Julien Mena, Emanuela S. Milani, Sandra Goetze, Cinzia Esposito, Jacobo Sarabia del Castillo, Anja L. Frei, Marta Nowak, Anja Irmisch, Jack Kuipers, Monica-Andreea Baciu-Drăgan, Pedro F. Ferreira, Franziska Singer, Anne Bertolini, Michael Prummer, Ulrike Lischetti, Rudolf Aebersold, Marina Bacac, Gerd Maass, Holger Moch, Michael Weller, Alexandre P. A. Theocharides, Markus G. Manz, Niko Beerenwinkel, Christian Beisel, Lucas Pelkmans, Berend Snijder, Bernd Wollscheid, Viola Heinzelmann, Bernd Bodenmiller, Mitchell P. Levesque, Viktor H. Koelzer, Gunnar Rätsch, Reinhard Dummer, Andreas Wicki
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Abstract

There is limited evidence supporting the feasibility of using omics and functional technologies to inform treatment decisions. Here we present results from a cohort of 116 melanoma patients in the prospective, multicentric observational Tumor Profiler (TuPro) precision oncology project. Nine independent technologies, mostly at single-cell level, were used to analyze 126 patient samples, generating up to 500 Gb of data per sample (40,000 potential markers) within 4 weeks. Among established and experimental markers, the molecular tumor board selected 54 to inform its treatment recommendations. In 75% of cases, TuPro-based data were judged to be useful in informing recommendations. Patients received either standard of care (SOC) treatments or highly individualized, polybiomarker-driven treatments (beyond SOC). The objective response rate in difficult-to-treat palliative, beyond SOC patients (n = 37) was 38%, with a disease control rate of 54%. Progression-free survival of patients with TuPro-informed therapy decisions was 6.04 months, (95% confidence interval, 3.75–12.06) and 5.35 months (95% confidence interval, 2.89–12.06) in ≥third therapy lines. The proof-of-concept TuPro project demonstrated the feasibility and relevance of omics-based tumor profiling to support data-guided clinical decision-making. ClinicalTrials.gov identifier: NCT06463509.

Abstract Image

多组学肿瘤分析指导黑色素瘤治疗的可行性
有有限的证据支持使用组学和功能技术为治疗决策提供信息的可行性。在此,我们报告了来自116名黑色素瘤患者的前瞻性、多中心观察性肿瘤分析器(TuPro)精确肿瘤学项目的结果。9项独立的技术(主要在单细胞水平)用于分析126例患者样本,在4周内生成每个样本高达500gb的数据(40,000个潜在标记物)。在已建立的和实验性的标记物中,分子肿瘤委员会选择了54种来告知其治疗建议。在75%的情况下,基于tupro的数据被认为对提供建议有用。患者接受标准护理(SOC)治疗或高度个性化、多生物标志物驱动的治疗(SOC之外)。在SOC以外难以治疗的姑息治疗患者(n = 37)中,客观缓解率为38%,疾病控制率为54%。接受tupro告知治疗决定的患者的无进展生存期为6.04个月(95%可信区间,3.75-12.06),≥3个治疗线的患者的无进展生存期为5.35个月(95%可信区间,2.89-12.06)。TuPro项目的概念验证证明了基于组学的肿瘤分析的可行性和相关性,以支持数据指导的临床决策。ClinicalTrials.gov识别码:NCT06463509。
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来源期刊
Nature Medicine
Nature Medicine 医学-生化与分子生物学
CiteScore
100.90
自引率
0.70%
发文量
525
审稿时长
1 months
期刊介绍: Nature Medicine is a monthly journal publishing original peer-reviewed research in all areas of medicine. The publication focuses on originality, timeliness, interdisciplinary interest, and the impact on improving human health. In addition to research articles, Nature Medicine also publishes commissioned content such as News, Reviews, and Perspectives. This content aims to provide context for the latest advances in translational and clinical research, reaching a wide audience of M.D. and Ph.D. readers. All editorial decisions for the journal are made by a team of full-time professional editors. Nature Medicine consider all types of clinical research, including: -Case-reports and small case series -Clinical trials, whether phase 1, 2, 3 or 4 -Observational studies -Meta-analyses -Biomarker studies -Public and global health studies Nature Medicine is also committed to facilitating communication between translational and clinical researchers. As such, we consider “hybrid” studies with preclinical and translational findings reported alongside data from clinical studies.
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