Clinical utility of next-generation sequencing-based ctDNA testing for common and novel<i> ALK</i> fusions

Simple item page
dc.contributor.authorMondaca, Sebastian
dc.contributor.authorLebow, Emily S.
dc.contributor.authorNamakydoust, Azadeh
dc.contributor.authorRazavi, Pedram
dc.contributor.authorReis-Filho, Jorge S.
dc.contributor.authorShen, Ronglai
dc.contributor.authorOffin, Michael
dc.contributor.authorTu, Hai-Yan
dc.contributor.authorMurciano-Goroff, Yonina
dc.contributor.authorXu, Chongrui
dc.contributor.authorMakhnin, Alex
dc.contributor.authorMartinez, Andres
dc.contributor.authorPavlakis, Nick
dc.contributor.authorClarke, Stephen
dc.contributor.authorItchins, Malinda
dc.contributor.authorLee, Adrian
dc.contributor.authorRimner, Andreas
dc.contributor.authorGomez, Daniel
dc.contributor.authorRocco, Gaetano
dc.contributor.authorChaft, Jamie E.
dc.contributor.authorRiely, Gregory J.
dc.contributor.authorRudin, Charles M.
dc.contributor.authorJones, David R.
dc.contributor.authorLi, Mark
dc.contributor.authorShaffer, Tristan
dc.contributor.authorHosseini, Seyed Ali
dc.contributor.authorBertucci, Caterina
dc.contributor.authorLim, Lee P.
dc.contributor.authorDrilon, Alexander
dc.contributor.authorBerger, Michael F.
dc.contributor.authorBenayed, Ryma
dc.contributor.authorArcila, Maria E.
dc.contributor.authorIsbell, James M.
dc.contributor.authorLi, Bob T.
dc.date.accessioned2025-01-20T22:10:36Z
dc.date.available2025-01-20T22:10:36Z
dc.date.issued2021
dc.description.abstractObjectives: Liquid biopsy for plasma circulating tumor DNA (ctDNA) next-generation sequencing (NGS) can detect ALK fusions, though data on clinical utility of this technology in the real world is limited. Materials and Methods: Patients with lung cancer without known oncogenic drivers or who had acquired resistance to therapy (n = 736) underwent prospective plasma ctDNA NGS. A subset of this cohort (n = 497) also had tissue NGS. We evaluated ALK fusion detection, turnaround time (TAT), plasma and tissue concordance, matching to therapy, and treatment response. Results: ctDNA identified an ALK fusion in 21 patients (3%) with a variety of breakpoints and fusion partners, including EML4, CLTC, and PON1, a novel ALK fusion partner. TAT for ctDNA NGS was shorter than tissue NGS (10 vs. 20 days; p < 0.001). Among ALK fusions identified by ctDNA, 93% (13/14, 95% CI 66%- 99%) were concordant with tissue evaluation. Among ALK fusions detected by tissue NGS, 54% (13/24, 95% CI 33%-74%) were concordant with plasma ctDNA. ctDNA matched patients to ALK-directed therapy with subsequent clinical response, including four patients matched on the basis of ctDNA results alone due to inadequate or delayed tissue testing. Serial ctDNA analysis detected MET amplification (n = 2) and ALK G1202R mutation (n = 2) as mechanisms of acquired resistance to ALK-directed therapy. Conclusion: Our findings support a complementary role for ctDNA in detection of ALK fusions and other alterations at diagnosis and therapeutic resistance settings.
dc.fuente.origenWOS
dc.identifier.doi10.1016/j.lungcan.2021.06.018
dc.identifier.eissn1872-8332
dc.identifier.issn0169-5002
dc.identifier.urihttps://doi.org/10.1016/j.lungcan.2021.06.018
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/94380
dc.identifier.wosidWOS:000685268300010
dc.language.isoen
dc.pagina.final73
dc.pagina.inicio66
dc.revistaLung cancer
dc.rightsacceso restringido
dc.subjectLiquid biopsy
dc.subjectCirculating tumor DNA
dc.subjectNext generation sequencing
dc.subjectALK fusion
dc.subject.ods03 Good Health and Well-being
dc.subject.odspa03 Salud y bienestar
dc.titleClinical utility of next-generation sequencing-based ctDNA testing for common and novel<i> ALK</i> fusions
dc.typeartículo
dc.volumen159
sipa.indexWOS
sipa.trazabilidadWOS;2025-01-12
Files
Collections
Artículos de revistas