Clinical benefit for clinical sequencing using cancer panel testing

Abstract

Background: Clinical sequencing using a panel of genes has recently been applied worldwide for patients with refractory solid tumors, but the significance of clinical sequencing using gene panel testing remains uncertain. Here we sought to clarify the feasibility and utility of clinical sequencing in the treatment of refractory tumors at our hospital.

Methods: A total of 39 patients with advanced solid tumors treated at our hospital between 2018 and 2020 were enrolled in the clinical sequencing. Among them, we identified 36 patients whose tissue samples were of suitable quality for clinical sequencing, and we analyzed the genomic profiles of these tumors.

Results: Pathogenic alterations were detected in 28 (78%) of the 36 patients. The most common mutation was TP53 (55%), followed by KRAS (22%), and the highest frequency of gene amplification was ERBB2 (17%). Nine of the 36 patients were identified as candidates for novel molecular-targeted therapy based on their actionable gene alterations, but only one case ended up receiving novel targeted therapy following the genetic tests.

Conclusions: Our current results suggested that clinical sequencing might be useful for the detection of pathogenic alterations and the management of additional cancer treatment. However, molecular target based on actionable genomic alteration does not always bridge to subsequent therapy due to clinical deterioration, refusal for unapproved drug, and complexity of clinical trial access. Both improved optimal timing of clinical sequencing and a consensus about its off-label use might help patients receive greater benefit from clinical sequencing.

Fig 1. Venn diagram of gene lists overlap by four types of panel testing.

A, The Venn diagram of the distribution of 324 genes targeted for all exons or hotspot regions in four panels. B, The Venn diagram of the distribution of druggable genes listed in four panels.

Fig 2. Pathogenic gene alterations in the 36 patients enrolled in clinical sequencing.

A, Among 36 patients, a total of 7 mutated genes that harbored a point mutation or copy number variation were detected in at least 2 patients. Genome signatures such as the TMB are also described in the list. B, Missense mutation, a mutation in codon 777 (Valine → Leucine), was located on the protein kinase position on a liner protein of ERBB2.

Fig 3. Survival curve of post-panel testing cases.

A, Half of 31 patients died within 1 year after the panel testing. B, The 1-year survival rate of the patients with GI cancer was 87.5%. C, The 1-year survival rate of the patients with pancreato-biliary was 25%. PB means pancreato-biliary.