The combined analysis of solid and liquid biopsies provides additional clinical information to improve patient care

Abstract

Aim: To investigate if the genetic information provided by sequencing of both solid and liquid biopsies can shed light on tumor heterogeneity, and to understand the clinical usefulness of adding blood profiling to standard tissue analysis in cancer care. Methods:Data from 351 patients with stage IV solid tumors for whom molecular profiling of their solid and liquid biopsies was available were studied, with a focus on the discrepant molecular information found between tissue and blood samples. Results:In 86% of patients, solid and liquid biopsies provided different molecular information. Discrepant gene mutations with a functional impact on the corresponding protein were studied in detail. In 97% of cases, these additional mutations provided clinical value, mainly predicting sensitivity or resistance to targeted therapies. Specifically, 42% of the mutations found only in the liquid biopsy were directly predictive of approved therapies (80% targeted therapies), while 54% were inclusion criteria for molecularly-matched trials. Conclusion:This study suggests that the addition of blood profiling should be considered in routine clinical oncology, especially for patients with metastatic disease where integrated analysis of solid and liquid biopsies provides a more complete characterization of tumor heterogeneity and provides valuable clinical information for patient treatment.

Molecular analysis of circulating tumor DNA from breast cancer patients before and after surgery and following adjuvant chemotherapy

“…The advantages of ctDNA analysis and the liquid biopsy were also demonstrated by Finzel et al ( 43 ), who studied data of 351 patients with stage IV solid tumors, including BC, focusing on the discordant gene mutations identified between FFPE blocks and ctDNA from blood samples. The authors detected different molecular alterations between tissue and liquid biopsies in 86% of patients.…”

“…However, 42% of the mutations detected only in the liquid biopsy had clinical relevance in prediction of sensitivity or resistance to administered targeted therapies. The combined assessment of liquid and solid biopsies enables better characterization of tumor heterogeneity and important information for patient therapy ( 43 ).…”

Detection of Somatic Mutations with ddPCR from Liquid Biopsy of Colorectal Cancer Patients

“…We propose the supplemental approach similar to the study by Finzel et al [ 48 ], where tissue and liquid biopsy were tested retrospectively on a set of patients with tumor stage IV who failed at least one line of therapy. They have shown that testing only tissue biopsy misdiagnosed a significant number of patients due to tumor heterogeneity.…”

Current Advances in Clinical Application of Liquid Biopsy

“…In another study, combined analysis of solid (192 genes) and liquid biopsies (27 genes) (OncoSTRAT&GO™, OncoDNA, Gosselies, Belgium), only found 40% of variants to be shared between the solid and liquid biopsy, with 51% of variants being exclusive to tissue and 9% to blood [62]. The liquid exclusive variants increased to 14% after a year from tissue sampling reflecting temporal heterogeneity [62]. The disparity in mutation calling may be a result of distinct shedding rates across tumour stage and types or sensitivity of the ctDNA assay.…”