Prognostic Value of the Pace of Tumor Progression as Assessed by Serial 18F-FDG PET/CT Scan and Liquid Biopsy in Refractory Colorectal Cancer: The CORIOLAN Trial

Abstract

Introduction: Decision making in refractory colorectal cancer (rCRC) is challenging, with limited data available to predict patient outcome. We conducted a study to assess the pace of cancer progression as a potential prognostic and decision tool. Methods: CORIOLAN was a prospective, single-center, single-arm trial recruiting refractory CRC patients with an ECOG performance status of ≤1 and an estimated life expectancy of ≥12 weeks. 18 fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan and blood sample collection were carried out at baseline and after 2 weeks with no cancer treatment given between these timepoints. The primary objective was to evaluate the association between pace of cancer progression as defined by changes of the whole-body metabolically active tumor volume (WB-MATV) and overall survival (OS). Exploratory objectives included evaluation of the prognostic value of circulating cell-free DNA (cfDNA), circulating tumor cells (CTCs) and carcinoembryonic antigen (CEA). Results: 47 eligible patients who had received a median number of 5 (range 2–8) prior treatments were enrolled. At the time of analysis, 45 deaths had occurred, with 26% of patients dying within 12 weeks. The median OS was 6.3 months (range 0.4–14.3). The median relative delta between WB-MATV at baseline and 2 weeks was +21%. Changes of WB-MATV, however, failed to predict OS (hazard ratio (HR) 1.3, p = 0.383). Similarly, no association was observed between changes of any of the circulating biomarkers investigated and prognosis. By contrast, high WB-MATV (4.2 versus 9.4 months; HR 3.1, p = 0.003), high CEA (4.4 versus 7.0 months; HR 1.9, p = 0.053), high cfDNA (4.7 versus 7.0 months; HR 2.2, p = 0.015) and high CTC count (3.3 versus 7.5 months; HR 6.5, p < 0.001) at baseline were associated with worse OS. Conclusions: In this study, approximately 1 out of 4 refractory CRC patients who were judged to have a life expectancy >12 weeks actually died within 12 weeks. Baseline assessment of WB-MATV, cfDNA, CTCs and CEA, but not early change evaluation of the same, may help to refine patient prognostication and guide management decisions.

Circulating Tumour Cells as Prognostic Biomarkers in Colorectal Cancer: A Systematic Review

“…These studies all reported a significant correlation between baseline "high CTC" status and reduced survival. Camera et al, 2020 [17], similarly reported a prognostic difference in the presence of disease refractory to standard treatment or unresectable CRC. Coumans et al, 2012 [6], reported that survival for patients with metastatic CRC patients with CTCs is reduced by 6.6 months for each 10-fold CTC increase.…”

Prognostic Value of Circulating Cytokines in Chemorefractory Colorectal Cancer

“…The discovery cohort included eligible patients from the CORIOLAN trial and CHRONOS & KAIROS study. The former investigated the association between the natural pace of tumor progression (as indicated by tumor metabolic changes on serial 18F-FDG PET scans) and survival in chemorefractory CRC [16]. Following a 14-day observation period without any active anti-cancer therapy, patients from this trial could be treated off-study based on local standards.…”

Liquid Biopsy in Advanced Colorectal Cancer: Clinical Applications of Different Analytes

“…Likewise, predictive and prognostic relationships were found, with worse median Progressive-Free Survival (mPFS) and mOS in both patients with poor baseline CTCs (mPFS 4.5 months vs. 7.9 months; p = 0.0002; mOS 9.4 months vs. 18.5 months; p < 0.0001) and those with persistently elevated CTCs throughout treatment [73]. Another study by Camera et al, focusing on the dynamic evolution of biomarkers (cfDNA, CEA, and CTC), as well as radiological changes as prognostic factors of OS in mCRC patients, failed to show a significant association with outcomes, while only baseline elevation of such biomarkers, especially CTC, predicted worse OS (HR 6.5) [37,74].…”