Added-value of whole exome and RNA Sequencing in advanced and refractory cancer patients with no molecular-based treatment recommendation based on a 90-gene panel release_dvzg4yuyqrd55ilplsb6ee37km

Abstract

Abstract Importance: While comprehensive tumor molecular profile by whole exome and RNA sequencing (WES/RNA-Seq) is now feasible in routine practice, it remains unclear whether this increases therapeutic options as compared to a more limited targeted gene panel (TGP) plus array-based comparative genomic hybridization (aCGH) in advanced cancer patients. Objective: To determine the added value of WES/RNA-Seq in advanced and refractory cancer patients who had no molecular-based treatment recommendation (MBTR) based on a TGP/aCGH in the course of a clinical trial. Design: Retrospective analysis. Setting: Single center. Participants: We selected 50 patients previously included in the PROFILER trial (<jats:ext-link xmlns:xlink="http://www.w3.org/1999/xlink" ext-link-type="clintrialgov" xlink:href="NCT01774409">NCT01774409</jats:ext-link>) for which no molecular-based therapy could be recommended in the course 65 of the clinical trial based on a targeted 90-gene panel and aCGH. For each patient, the frozen tumor sample mirroring the FFPE sample used for TGP/aCGH analysis were processed for WES and RNA-Seq. Data from TGP/aCGH were reanalyzed and together with WES/RNA-Seq, findings were simultaneously discussed at a new molecular tumor board (MTB). Main outcomes and Measures: MBTR based on TGP/aCGH versus WES/RNA-Seq were compared. Results: After exclusion of variants of unknown significance, a total of 167 somatic molecular alterations were identified in 50 patients (median: 3; range: 1-10). Out of these 167 relevant molecular alterations reported by the biologist, 51 (31%) were common to both TGP/aCGH and WES/RNA-Seq, 19 (11%) were identified by the TGP/aCGH only and 97 (58%) were identified by WES/RNA-Seq only, including 2 fusion transcripts in two patients. A MBRT was provided in 4/50 (8%) patients using the information from TGP/aCGH vs. 9/50 (18%) patients using WES/RNA-Seq findings. Three patients had similar recommendations based on TGP/aCGH and WES/RNA-Seq. Conclusion and Relevance: In advanced and refractory cancer patients in whom no MBRT was recommended from TGP/aCGH, WES/RNA-Seq allowed to identify more alterations which may in turn, in a limited fraction of patients, lead to new MBRT.
In application/xml+jats format

Archived Files and Locations