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
Authors: Dufresne Armelle , Attignon Valéry , Ferrari Anthony , Tonon Laurie , Tabone-Eglinger Séverine , Cassier Philippe , Trédan Olivier , Corradini Nadège , Vinceneux Armelle , Swalduz Aurélie , Viari Alain , Chabaud Sylvie , Pérol David , Blay Jean Yves , Saintigny Pierre 
Published: February 2022

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 (NCT01774409) for which no molecular-based therapy could be recommended in the course 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.

Key Points

Question

Does WES/RNA-Seq provide additional targeted treatment guidance for advanced cancer patients with no molecular-based treatment recommendation (MBTR) from a 90-tumor gene panel (TGP) sequencing and array-based comparative genomic hybridization (aCGH)?

Findings

For fifty advanced cancer patients included in the PROFILER trial with no treatment recommendation based on a TGP/aCGH, frozen tumor sample was processed for WES and RNA-Seq. MBTR was given in 4/50 (8%) patients using the reanalyzed TGP/aCGH vs. 9/50 (18%) patients using WES/RNA-Seq findings.

Meanings

WES/RNA-Seq increased the number of patients with MBTR as compared to a TGP/aCGH screening to yet only a minority of patients.