Plasma ctDNA is a tumor tissue surrogate and enables clinical-genomic stratification of metastatic bladder cancer
Vandekerkhove, Gillian; Lavoie, Jean Michel; Annala, Matti; Murtha, Andrew J.; Sundahl, Nora; Walz, Simon; Sano, Takeshi; Taavitsainen, Sinja; Ritch, Elie; Fazli, Ladan; Hurtado-Coll, Antonio; Wang, Gang; Nykter, Matti; Black, Peter C.; Todenhöfer, Tilman; Ost, Piet; Gibb, Ewan A.; Chi, Kim N.; Eigl, Bernhard J.; Wyatt, Alexander W. (2021)
Vandekerkhove, Gillian
Lavoie, Jean Michel
Annala, Matti
Murtha, Andrew J.
Sundahl, Nora
Walz, Simon
Sano, Takeshi
Taavitsainen, Sinja
Ritch, Elie
Fazli, Ladan
Hurtado-Coll, Antonio
Wang, Gang
Nykter, Matti
Black, Peter C.
Todenhöfer, Tilman
Ost, Piet
Gibb, Ewan A.
Chi, Kim N.
Eigl, Bernhard J.
Wyatt, Alexander W.
2021
184
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tuni-202102041929
https://urn.fi/URN:NBN:fi:tuni-202102041929
Kuvaus
Peer reviewed
Tiivistelmä
Molecular stratification can improve the management of advanced cancers, but requires relevant tumor samples. Metastatic urothelial carcinoma (mUC) is poised to benefit given a recent expansion of treatment options and its high genomic heterogeneity. We profile minimally-invasive plasma circulating tumor DNA (ctDNA) samples from 104 mUC patients, and compare to same-patient tumor tissue obtained during invasive surgery. Patient ctDNA abundance is independently prognostic for overall survival in patients initiating first-line systemic therapy. Importantly, ctDNA analysis reproduces the somatic driver genome as described from tissue-based cohorts. Furthermore, mutation concordance between ctDNA and matched tumor tissue is 83.4%, enabling benchmarking of proposed clinical biomarkers. While 90% of mutations are identified across serial ctDNA samples, concordance for serial tumor tissue is significantly lower. Overall, our exploratory analysis demonstrates that genomic profiling of ctDNA in mUC is reliable and practical, and mitigates against disease undersampling inherent to studying archival primary tumor foci. We urge the incorporation of cell-free DNA profiling into molecularly-guided clinical trials for mUC.
Kokoelmat
- TUNICRIS-julkaisut [17001]