Clinical cancer research : an official journal of the American Association for Cancer Research · 2026
Longitudinal liquid biopsy and matched radiomic analysis indicated resistance mechanisms of patients with biliary tract cancer undergoing systemic treatment.
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Tesini Giulia, Greaves Jack, Ammirabile Angela, Cavinato Lara, Amato Francesco, Rae Colin, Marco Sergi, Mahdieh Mobina, Knight Olivia, Zanuso Valentina, McHaffie Sophie, Vita Francesca, Prete Maria Giuseppina, MacMillian Antonia, Allan Karen, Herzyk Pawel, Galbraith Julie, Meenan Rosemary, Henderson Margaret, Campbell Sophia, Lampis Andrea, Chesler Louis, Fassan Matteo, Kendall Timothy J, Rimassa Lorenza, Viganò Luca, Braconi Chiara
Аннотация
BACKGROUND AND AIMS: Data on the evolution of molecular alterations during first-line systemic anti-cancer treatment (SACT) are lacking for biliary tract cancers. Liquid biopsy and radiomics are non-invasive tools that could provide insights.
METHODS: Plasma samples collected at baseline (N=39) and progressive disease (PD, N=30) were subjected to NGS panel covering SNV and CNV [Avenio ctDNA-Expanded-kit]. CT scans were reviewed for total tumor burden (TTB) analysis and for an exploratory radiomic analysis.
RESULTS: cfDNA concentration correlated with TTB (p=0.0003). Intrahepatic cholangiocarcinomas (iCCA) had larger TTB (p=0.034) and higher number of alterations (p=0.02). cfDNA concentration or median dominant VAF did not correlate with outcomes. Baseline MET SNVs (p=0.07) and ERBB2 CNVs (p=0.03) were associated with shorter time to progression (TTP). iCCA frequently displayed a heterogeneous molecular response to SACT. Patients with increasing CNV score for EGFR [TTP: 4.1 vs 9.5 months, p=0.003; overall survival (OS): 10.1 vs 21.6 months, p=0.02] and MET [TTP: 4.2 vs 10.1 months, p=0.01; OS: 9.5 vs 20.2 months, p=0.06] had worse outcomes than those with decreasing score during SACT. Cases with PD driven by EGFR and MET were associated with selected baseline radiomic features: NGTDM Coarseness (p=0.041), GLSZM Zone Size Entropy (p=0.028) for EGFR; GLRLM Short Run Emphasis (p=0.034), GLRLM Run Length Variance (p=0.017), GLRLM Run Entropy (p=0.028), GLSZM Large Zone Emphasis (p=0.019) for MET.
CONCLUSION: Liquid biopsy identified potential primary (MET SNVs/ERBB2 CNVs) and secondary (EGFR/MET CNVs) resistance mechanisms to platinum-based SACT. Radiomics provided an early correlation with molecular evolution.
METHODS: Plasma samples collected at baseline (N=39) and progressive disease (PD, N=30) were subjected to NGS panel covering SNV and CNV [Avenio ctDNA-Expanded-kit]. CT scans were reviewed for total tumor burden (TTB) analysis and for an exploratory radiomic analysis.
RESULTS: cfDNA concentration correlated with TTB (p=0.0003). Intrahepatic cholangiocarcinomas (iCCA) had larger TTB (p=0.034) and higher number of alterations (p=0.02). cfDNA concentration or median dominant VAF did not correlate with outcomes. Baseline MET SNVs (p=0.07) and ERBB2 CNVs (p=0.03) were associated with shorter time to progression (TTP). iCCA frequently displayed a heterogeneous molecular response to SACT. Patients with increasing CNV score for EGFR [TTP: 4.1 vs 9.5 months, p=0.003; overall survival (OS): 10.1 vs 21.6 months, p=0.02] and MET [TTP: 4.2 vs 10.1 months, p=0.01; OS: 9.5 vs 20.2 months, p=0.06] had worse outcomes than those with decreasing score during SACT. Cases with PD driven by EGFR and MET were associated with selected baseline radiomic features: NGTDM Coarseness (p=0.041), GLSZM Zone Size Entropy (p=0.028) for EGFR; GLRLM Short Run Emphasis (p=0.034), GLRLM Run Length Variance (p=0.017), GLRLM Run Entropy (p=0.028), GLSZM Large Zone Emphasis (p=0.019) for MET.
CONCLUSION: Liquid biopsy identified potential primary (MET SNVs/ERBB2 CNVs) and secondary (EGFR/MET CNVs) resistance mechanisms to platinum-based SACT. Radiomics provided an early correlation with molecular evolution.