Liquid biopsy in oncology: a consensus statement of the Spanish Society of Pathology and the Spanish Society of Medical Oncology

Abstract

The proportion of cancer patients with tumours that harbour a potentially targetable genomic alteration is growing considerably. The diagnosis of these genomic alterations can lead to tailored treatment at the onset of disease or on progression and to obtaining additional predictive information on immunotherapy efficacy. However, in up to 25% of cases, the initial tissue biopsy is inadequate for precision oncology and, in many cases, tumour genomic profiling at progression is not possible due to technical limitations of obtaining new tumour tissue specimens. Efficient diagnostic alternatives are therefore required for molecular stratification, which includes liquid biopsy. This technique enables the evaluation of the tumour genomic profile dynamically and captures intra-patient genomic heterogeneity as well. To date, there are several diagnostic techniques available for use in liquid biopsy, each one of them with different precision and performance levels. The objective of this consensus statement of the Spanish Society of Pathology and the Spanish Society of Medical Oncology is to evaluate the viability and effectiveness of the different methodological approaches in liquid biopsy in cancer patients and the potential application of this method to current clinical practice. The experts contributing to this consensus statement agree that, according to current evidence, liquid biopsy is an acceptable alternative to tumour tissue biopsy for the study of biomarkers in various clinical settings. It is therefore important to standardise pre-analytical and analytical procedures, to ensure reproducibility and generate structured and accessible clinical reports. It is essential to appoint multidisciplinary tumour molecular boards to oversee these processes and to enable the most suitable therapeutic decisions for each patient according to the genomic profile.

Circulating immune biomarkers in peripheral blood correlate with clinical outcomes in advanced breast cancer

“…Consequently, the balance between immune inhibitory and stimulatory signals is determinant to explain the final effect, anergy or activation of the immune system against cancer cells. Density and function of some immune cell populations seem related to the response to treatment and prognosis of cancer 4 – 7 and, interestingly, they can be detected and measured not just in TME but even in peripheral blood, what renders many advantages over tissue biopsies 8 . At this point, myeloid derived suppressor cells (MDSCs) and different lymphocyte subpopulations, such as regulatory T cells (Tregs) 4 , activated CD4 + and CD8 + T lymphocytes (expressing OX40) or inhibited T lymphocytes (expressing PD-1) 9 , 10 , and other subset of cells can be measured in peripheral blood of patients with BC 2 , 5 , 11 – 13 .…”

ctDNA as a Cancer Biomarker: A Broad Overview

“…DNA extracted from the serum is variably fragmented, but representative sequences with characteristic cancer-related aberrations could reproducibly demonstrate suitable amplification and accurate sequencing (Ma et al, 2017). Recently, there has been consensus in the literature that ctDNA obtained by liquid biopsy is a convenient carrier of the actual genetic composition and is potentially more informative than tissue-derived nucleic acids archived from the time of diagnosis (Li et al, 2019;Remon et al, 2019;Vitiello et al, 2019). Additionally, ctDNA is useful for finding therapeutic targets after several cycles of therapy (Bhangu et al, 2018;Garlan et al, 2017).…”

Treatment strategy optimization for patients with non-small-cell lung cancer harboring EGFR mutation: a Delphi consensus

“…Although tumor tissue is the most relevant source of information, unfortunately in up to 25% of cases [ 13 ], the initial tissue biopsy is inadequate for precision oncology. In this context, the use of liquid biopsy is an efficient diagnostic alternative which can be considered at the time of initial diagnosis in patients who need tumor molecular profiling, specially when tumor tissue is scarce, unavailable, or a delay greater than 2 weeks in obtaining tumor tissue is expected [ 14 , 15 ]. The one statement with no consensus was related to the importance of disease stage versus molecular diagnosis.…”