Comparative Study of Whole Genome/Transcriptome Sequencing vs. Panel Sequencing in Cancer Treatment

The study enrolled twenty patients with one hematologic and eighteen different solid tumor entities, who underwent WES/WGS ± TS and panel sequencing. The median age was 46 years, with a median of one prior systemic therapy. The clinical relevance of molecular findings was assessed by translational oncologists. The study found that WES/WGS ± TS provided a broader range of therapy recommendations (TRs) based on a wider array of biomarkers (BMs), including RNA expression data and composite biomarkers like DNA mutational signatures and HRD scores, which were not fully captured by panel sequencing.

In the MASTER 1 analysis, 68 TRs were issued, with a median of 3.5 TRs per patient, based on 176 BMs from 14 different categories of alterations. The MASTER 2 analysis revealed 61 TRs with a median of 3.0 TRs per patient, based on 124 BMs. Panel sequencing recommended 51 TRs with a median of 2.5 TRs per patient, based on 75 BMs from seven different categories.

Comparisons showed that 47.1% of TRs from MASTER 1 matched with 62.8% of TRs from the panel analysis, with 90.6% based on the same BMs. The study highlighted the limitations of panel sequencing in detecting certain alterations, such as CNVs and specific gene fusions, which were crucial for some therapy recommendations. The study concludes that while panel sequencing offers practical advantages, WES/WGS ± TS provides a more comprehensive molecular profiling, essential for the treatment of rare and advanced cancers.