18F-FDG PET scan and liquid biopsy as tools to assess the pace of tumor progression and to predict overall survival (OS) in refractory colorectal cancer (rCRC): The CORIOLAN trial

e16012 Background: Decision making in rCRC patients (pts) who have exhausted all available therapies is challenging. Clinical trials, treatment re-challenge and best supportive care are possible options. There are limited data, however, to predict pt outcome and guide treatment choices. Methods: CORIOLAN was a prospective, single-centre, single-arm trial. Eligible pts had to have an ECOG PS of ≤1, a life expectancy of ≥12 weeks (wks) and had to have received prior standard chemotherapy and targeted agents. No cancer treatment was allowed within 4 wks prior to study entry. 18F-FDG PET scan and blood sample collection were carried out at baseline and after 2 wks. No treatment was given between these timepoints, while further management was left to the treating physician. The primary objective was to evaluate the association between tumour metabolic progression index as defined by changes of the whole-body metabolically active tumour volume (WB-MATV) and OS. Exploratory objectives included evaluation of the prognostic value of circulating biomarkers such as cell-free DNA (cfDNA), circulating tumour cells (CTCs, CellTracks Analyzer II, CellSearch) and CEA. Validated cut-off values, Kaplan-Meier method, Cox proportional hazards model and logrank tests were used (R version 3.5.1). Results: From 2012 to 2018, 47 eligible pts were enrolled. Median age: 65 years (38-82). ECOG PS 1: 64%. Males: 53%. Left-sided tumours: 71%. Metastases: lung (83%), liver (66%), lymph-nodes (45%), peritoneum (30%), bone (21%). Known RAS/BRAF mutations: 57%/0%. Median number of prior treatments: 5 (2-8). At the time of analysis, 45 deaths had occurred, with 26% of pts dying within 12 wks. The median relative delta between WB-MATV at baseline and after 2 wks was +21%. Changes of WB-MATV, however, failed to predict OS (p≥0.383). Similarly, no association was observed between changes of any of the circulating biomarkers investigated and prognosis. By contrast, low WB-MATV (9.4 vs 4.2 months, HR 0.65, p = 0.003), low cfDNA (7.0 vs 4.7 months, HR 0.58, p = 0.015), low CTC count (7.5 vs 3.3 months, HR 0.67, p < 0.001) and low CEA (7.0 vs 4.4 months, HR 0.58, p = 0.053) at baseline were associated with longer OS. Conclusions: This study confirms the inaccuracy of life expectancy estimation for rCRC pts based on a physician judgement largely relying on conventional criteria. Baseline assessment of WB-MATV, cfDNA, CTCs and CEA, but not early change evaluation of the same, may help to refine pt prognostication and guide management decisions. Clinical trial information: NCT01591590 .