Liquid Biopsy as a tool for diagnosing and controlling therapy for solid tumors – NeoRect study

Supporting personalised (patient-related “tailor-made”) therapy decisions based on the patient-specific molecular profile of tumors is an important focus of the research and individualized care of the ICCA at the University Hospital Augsburg.

With the so-called “Liquid Biopsy” tumor DNA (ctDNA) circulating in the blood can be analyzed from a simple blood sample as for routine laboratory diagnostics. Thus, changes in the tumor genome (the “genetic information” in the tumor cells) such as mutations or so-called epigenetic aberrations can be characterized, without which one has to obtain a tumor sample from the tissue with corresponding risks and strains on the individual patient. This Liquid Biopsy has great potential as a biomarker for both prognosis estimation, early detection of relapse (recurrence), follow-up under therapy and detection of resistance to certain drugs.

The clinical-practical applicability of this method has already been proven in various studies. In terms of sensitivity and scalability to detect a broad spectrum of mutations regardless of the localization of one or more tumor manifestations, Liquid Biopsy is continuously being further developed. One example is the NeoRect study we designed. In the Augsburg NeoRect study, patients with rectal cancer (stage II and III) are examined using liquid biopsy during pre-surgery (neoadjuvant) radiochemotherapy up to the time of surgery. The aim of this study is to identify patients who, already after neoadjuvant radiochemotherapy, achieve a complete disappearance of still living tumor tissue (complete pathological remission, pCR) and can therefore be fed a close-meshed follow-up (“active surveillance”) strategy instead of the surgical removal of the rectum. So far, however, there are no reliable clinical biomarkers for achieving pCR. In the first preliminary analyses of the NeoRect study (Claus R et al. DGHO 2019), we were able to show a correlation between the presence of ctDNA and the achievement of pCR after neoadjuvant radiochemotherapy.

We can currently conclude that ctDNA has the potential to be a predictive marker for identifying patients who reach pCR and could therefore be given a treatment strategy without rectum removal in the context of the NeoRect study. Based on this, we are currently developing a concept of integrating Liquid Biopsy into routine clinical care in Augsburg in order to integrate the diagnostic, prognostic and predictive potential of ctDNA into individual therapy recommendations and decisions.