Short summary

RECIST imaging has limitations in guiding metastatic cancer treatment. Circulating tumor DNA (ctDNA) offers a minimally invasive, more accurate alternative, reflecting treatment response and prognosis. In colorectal cancer, ctDNA reduces unnecessary chemotherapy and may better predict survival. A ctDNA-RECIST framework could enable earlier, more precise treatment decisions, improving outcomes and optimizing healthcare resources.

Rationale

Current methods for assessing treatment efficacy in metastatic cancer, primarily based on RECIST imaging criteria, are limited and often fail to correlate strongly with overall survival. Despite this, imaging remains the standard for guiding treatment decisions. However, circulating tumor DNA (ctDNA), detectable through blood samples, offers a promising alternative. CtDNA is minimally invasive, allows for frequent testing, and may provide a more accurate and timely assessment of treatment response than scans. In colorectal cancer, ctDNA has shown potential in identifying minimal residual disease and guiding adjuvant chemotherapy decisions. Recent results from the DYNAMIC trial demonstrated that ctDNA-guided treatment reduced unnecessary chemotherapy without increasing recurrence rates. In metastatic settings, ctDNA dynamics also show promise, though randomized trials are still lacking. Evidence suggests that a decrease in ctDNA levels after treatment correlates with better prognosis and may outperform radiologic assessments, particularly in predicting overall survival. A proposed ctDNA-RECIST framework aims to mirror traditional RECIST but based on ctDNA levels, defining response, progression, and stability using statistical confidence intervals. This approach could represent a paradigm shift in cancer care, allowing more personalized and effective treatment strategies for metastatic disease, while improving patient outcomes and optimizing healthcare resources. Aim To investigate ctDNA-RECIST guided treatment of metastatic cancer in a randomized trial.

Description of the cohort

Incurable metastatic gastrointestinal cancer, Indication for first or second-line systemic treatment

Data and biological material

Standard clinical data from patient journal and blood samples

Collaborating researchers and departments

Århus University Hospital

• Karen-Lise G Spindler

Department of Oncology