Support of a molecular tumour board by an evidence-based decision management system for precision oncology

被引：24

作者：

Lamping, Mario ^{[1
,2
,3
]}

Benary, Manuela ^{[2
,3
,4
,5
]}

Leyvraz, Serge ^{[1
,2
,3
]}

Messerschmidt, Clemens ^{[6
]}

Blanc, Eric ^{[6
]}

Kessler, Thomas ^{[7
]}

Schuette, Moritz ^{[5
,7
]}

Lenze, Dido ^{[2
,3
,4
]}

Joehrens, Korinna ^{[2
,3
,4
]}

Burock, Susen ^{[1
,2
,3
]}

Klinghammer, Konrad ^{[8
,9
,10
]}

Ochsenreither, Sebastian ^{[1
,2
,3
,8
,9
,10
]}

Sers, Christine ^{[2
,3
,4
]}

Schaefer, Reinhold ^{[1
,2
,3
,11
,12
]}

Tinhofer, Ingeborg ^{[11
,12
,13
]}

Beule, Dieter ^{[6
]}

Klauschen, Frederick ^{[2
,3
,4
]}

Yaspo, Marie-Laure ^{[7
,14
]}

Keilholz, Ulrich ^{[1
,2
,3
,11
,12
]}

Rieke, Damian T. ^{[1
,2
,3
,8
,9
,10
,15
]}

机构：

[1] Charite Univ Med Berlin, Charite Comprehens Canc Ctr, Charitepl 1, D-10117 Berlin, Germany

[2] Humboldt Univ, Freie Univ Berlin, Charitepl 1, D-10117 Berlin, Germany

[3] Berlin Inst Hlth, Charitepl 1, D-10117 Berlin, Germany

[4] Charite Univ Med Berlin, Dept Pathol, Charitepl 1, D-10117 Berlin, Germany

[5] Humboldt Univ, IRI Life Sci, Philippstr 13, D-10115 Berlin, Germany

[6] BIH, Core Unit Bioinformat, Anna Louisa Karsch Str 2, D-10178 Berlin, Germany

[7] Alacris Theranost GmbH, Max Planck Str 3, D-12489 Berlin, Germany

[8] Charite Univ Med Berlin, Campus Benjamin Franklin, Dept Hematol & Oncol, D-12203 Berlin, Germany

[9] Humboldt Univ, Freie Univ Berlin, Hindenburgdamm 30, D-12203 Berlin, Germany

[10] Berlin Inst Hlth, Hindenburgdamm 30, D-12203 Berlin, Germany

[11] German Canc Consortium DKTK, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

[12] German Canc Res Ctr, Neuenheimer Feld 280, D-69120 Heidelberg, Germany

[13] Charite Univ Med Berlin, Dept Radiooncol, Charitepl 1, D-10117 Berlin, Germany

[14] Max Planck Inst Mol Genet, Otto Warburg Lab Gene Regulat & Syst Biol Canc, Ihnestr 63, D-14195 Berlin, Germany

[15] BIH, Anna Louisa Karsch Str 2, D-10178 Berlin, Germany

来源：

EUROPEAN JOURNAL OF CANCER | 2020年 / 127卷

关键词：

Precision oncology; Molecular tumour board; Molecular tumour conference; Targeted therapy; Personalized therapy; SELUMETINIB PLUS DOCETAXEL; FIND POTENTIAL TARGETS; CELL LUNG-CANCER; PERSONALIZED MEDICINE; PHASE-II; PROGRAM; MULTICENTER; VARIANTS; THERAPY; IMPACT;

D O I：

10.1016/j.ejca.2019.12.017

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Background: Reliable and reproducible interpretation of molecular aberrations constitutes a bottleneck of precision medicine. Evidence-based decision management systems may improve rational therapy recommendations. To cope with an increasing amount of complex molecular data in the clinical care of patients with cancer, we established a workflow for the interpretation of molecular analyses. Methods: A specialized physician screened results from molecular analyses for potential biomarkers, irrespective of the diagnostic modality. Best available evidence was retrieved and categorized through establishment of an in-house database and interrogation of publicly available databases. Annotated biomarkers were ranked using predefined evidence levels and subsequently discussed at a molecular tumour board (MTB), which generated treatment recommendations. Subsequent translation into patient treatment and clinical outcomes were followed up. Results: One hundred patients were discussed in the MTB between January 2016 and May 2017. Molecular data were obtained for 70 of 100 patients (50 whole exome/RNA sequencing, 18 panel sequencing, 2 immunohistochemistry (IHC)/microsatellite instability analysis). The MTB generated a median of two treatment recommendations each for 63 patients. Thirtynine patients were treated: 6 partial responses and 12 stable diseases were achieved as best responses. Genetic counselling for germline events was recommended for seven patients. Conclusion: The development of an evidence-based workflow allowed for the clinical interpretation of complex molecular data and facilitated the translation of personalized treatment strategies into routine clinical care. The high number of treatment recommendations in patients with comprehensive genomic data and promising responses in patients treated with combination therapy warrant larger clinical studies. (C) 2019 Elsevier Ltd. All rights reserved.

引用

页码：41 / 51

页数：11

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