Short summary

The purpose of this study is to investigate if ctDNA progression (i.e. an increase in ctDNA) correlates with shorter overall survival, if ctDNA control correlates with objective response (see definition below), and if ctDNA response could be a surrogate endpoint for survival.

Rationale

Patients with metastatic disease may undergo several lines of palliative chemotherapy with the aim of prolonged survival and improved quality of life. As present the only tool for assessment of treatment effect is currently the Response Evaluation criteria In solid tumors (RECIST) comparing baseline status with imaging measures of lesions at defined treatment intervals (3-4 cycles).

It is well known that there is only a modest correlation between objective response by RECIST and oncologic outcome, and response is not a valid surrogate endpoint for overall survival. Hence, there is an obvious need for new biomarkers able to classify the patients into prognostic subgroups with the perspective of "the right treatment for the right patient at the right time" and being instrumental in the assessment of treatment effect.

From a theoretical point of view, ctDNA detected in blood holds several characteristics of an ideal tumor marker, being timely measured, minimally invasive, and easily accessible for repeated measurement with little discomfort to the patient. Hence, ctDNA can become a critical determinant in driving the care of cancer patients 1,2. The results of consecutive ctDNA analyses might facilitate personalized follow-up programs, add information to inconclusive scans, and spare patients of comprehensive interventions such as repeated tumor biopsies. In addition, ineffective treatments and the pertaining toxicity may be reduced with a more precise monitoring of treatment effect. The potential of ctDNA-guided treatment has been investigated in systemic treatment of several solid tumors 3. Lately the same promising tendencies of ctDNA as a prognostic biomarker are shown in immunotherapy 4.

ctDNA is a pan-cancer concept and methods for ctDNA analysis are developed and validated for many tumor types. Despite its advantages, however, ctDNA monitoring has not been implemented in the daily clinical practice for several reasons. Current knowledge is based on retrospective analyses and few prospective studies.

Our previous retrospective analysis of three different tumor types clearly underlined the importance of ctDNA response and suggested that it may serve as a surrogate endpoint for overall survival 5. On the other hand, early ctDNA progression seems to imply a poor prognosis (manuscript in preparation). The aim of the present study is to address these issues in a major prospective biomarker protocol.

Description of the cohort

400 patients with metastatic carcinoma of the colon, rectum, lung, pancreas, bile duct, or ovary, with planned systemic treatment (all lines).

Data and biological material

3 blood samples

Collaborating researchers and departments

UniDepartment of Oncology, Aarhus University Hospital. Department of Oncology and palliative care, Zealand University Hospital. Department of Oncology, Asklepios Tumorzentrum Hamburg, Germany