The molecular profiling of solid tumors by liquid biopsy: a position paper of the AIOM–SIAPEC-IAP–SIBioC–SIC–SIF Italian Scientific Societies

Abstract

The term liquid biopsy (LB) refers to the use of various biological fluids as a surrogate for neoplastic tissue to achieve information for diagnostic, prognostic and predictive purposes. In the current clinical practice, LB is used for the identification of driver mutations in circulating tumor DNA derived from both tumor tissue and circulating neoplastic cells. As suggested by a growing body of evidence, however, there are several clinical settings where biological samples other than tissue could be used in the routine practice to identify potentially predictive biomarkers of either response or resistance to targeted treatments. New applications are emerging as useful clinical tools, and other blood derivatives, such as circulating tumor cells, circulating tumor RNA, microRNAs, platelets, extracellular vesicles, as well as other biofluids such as urine and cerebrospinal fluid, may be adopted in the near future. Despite the evident advantages compared with tissue biopsy, LB still presents some limitations due to both biological and technological issues. In this context, the absence of harmonized procedures corresponds to an unmet clinical need, ultimately affecting the rapid implementation of LB in clinical practice. In this position paper, based on experts’ opinions, the AIOM–SIAPEC-IAP–SIBIOC–SIF Italian Scientific Societies critically discuss the most relevant technical issues of LB, the current and emerging evidences, with the aim to optimizing the applications of LB in the clinical setting.

SDK1-ALK Fusion in a Lung Adenocarcinoma Patient With Excellent Response to ALK Inhibitor Treatment: A Case Report

“…NGS is a valid approach able to detect sufficient gene alterations simultaneously, and it can be started with nucleic acids recovered from patients' cancer tissues in situ or liquid biopsy samples. According to the KWAY Italian multicenter cost evaluation research, the implementation of NGS saves personnel time spent to testing activities and lowers the overall cost of testing per patient (9,10). Fluorescence in situ hybridization and IHC are gold standards for ALK mutation testing.…”

Fatal Tumour Lysis Syndrome Induced by Brigatinib in a Lung Adenocarcinoma Patient Treated With Sequential ALK Inhibitors: A Case Report

“…In recent years, liquid biopsy has gradually become an alternative or complementary approach to tissue biopsy for diagnostic, predictive, and prognostic purposes. Compared with traditional tissue biopsy, liquid biopsy has notable advantages, such as its minimally invasive nature, ability to reflect tumour heterogeneity, and capacity to be repeatedly performed to realize dynamic monitoring of the disease (Russo et al, 2021). Liquid biopsy is particularly suitable for patients for whom sufficient tumour tissues cannot be obtained for molecular profiling.…”

Recent Advances in Liquid Biopsy of Brain Cancers

“…Considering the limitations of peripheral blood, another body fluid, CSF, is much closer to brain tissues physically and may reflect tumor burden more directly (De Mattos-Arruda et al, 2015). Circulating tumor DNA concentration is usually higher in CSF compared to plasma, which means variations or mutations of low frequency are more likely to be detected in the CSF, therefore makes CSF-based liquid biopsy more powerful in the clinic (Russo et al, 2021). For instance, one study shows that in HER2positive breast cancer patients with brain metastases, gene variations have higher levels in CSF than plasma for posttreatment monitoring (Siravegna et al, 2017a).…”