By Christian Rolfo, MD, PhD, MBAh, and Philip C. Mack, PhD
Posted: December 2017
In just the past decade, tremendous advancements in the treatment of metastatic non-small cell lung cancer (NSCLC) have been made due to the identification of targetable oncogenic molecular drivers on which the tumors are dependent for their growth and survival. Precision oncology—treating the patient with therapies predicted to be effective based on the specific molecular characteristics of their tumor—can add years of quality life for those patients.
Historically, tissue biopsy specimens have been used as the sole source of tumor molecular information, but unfortunately, adequate tissue is not always easy to obtain from all patients with advanced NSCLC. In addition, the necessity to monitor responses to treatment and to identify emergent molecular mechanisms of resistance has become increasingly important but is limited by the challenges of traditional tissue rebiopsies. In this context, the isolation of tumor-derived DNA, RNA and cells from the peripheral circulation (a concept termed liquid biopsy) is emerging as a versatile and powerful tool for the optimization of NSCLC clinical management via the identification of predictive biomarkers, either prior to treatment or at progression. However, despite several potential advantages, liquid biopsy is still far from completely replacing tissue biopsy, and its role in clinical practice needs to be precisely defined and validated.
For this reason, a multidisciplinary panel of International Association for the Study of Lung Cancer (IASLC) members, experts in the field of thoracic oncology and liquid biopsy, evaluated the current available evidence with the aim of producing a set of recommendations for the use of liquid biopsy for molecular analysis in order to guide the routine clinical management of advanced NSCLC patients.
The consensus statement will address:
• Blood sample acquisition and handling, plus subsequent extraction of circulating cell-free tumor DNA (cftDNA)
• Platforms for molecular analysis and requirements for their use
• Role in treatment-naive patients
• Monitoring treatment response
• Clinical value in patients with progressive disease
• Results reporting and molecular tumor boards
• Ethical considerations with regards to germline mutations and informed consent
• Role of liquid biopsy in immune oncology
• Molecular characterization of cft RNA and circulating tumor cells
• Liquid specimens beyond peripheral blood
The possibility of using a non-invasive method to understand and identify molecular targets and mechanisms of resistance for current drugs, both targeted agents and immunotherapies, will be extremely beneficial for patients, as will harnessing these strategies to identify new biomarkers. The future of liquid biopsies is undeniably exciting, but there is a need to more clearly understand the latest developments; therefore, this timely consensus statement will be published in an upcoming issue of the Journal of Thoracic Oncology, the official journal of the IASLC. ✦
Editor’s note. Murry W. Wynes, PhD, IASLC Director of Scientific Affairs, is acknowledged and thanked for his contributions to this article.