Summary
This pan-cancer analysis of 978 pretreatment and 171 on-treatment circulating tumour DNA samples across 16 advanced-stage tumour types examined the prognostic and predictive utility of ctDNA in patients receiving immune checkpoint blockade (durvalumab ± tremelimumab). Higher pretreatment VAF was associated with poorer overall survival and prognostic factors, whilst on-treatment reductions in VAF independently predicted longer survival, improved progression-free survival, and higher objective response rates. The authors propose a 'molecular response' concept integrating pretreatment and on-treatment ctDNA dynamics that predicted long-term survival comparably to radiologic response and permitted early identification of responders among radiologically stable patients.
Regional applicability
These findings on ctDNA biomarkers may inform clinical decision-making in UK cancer services and NHS oncology trials, though applicability would depend on access to ctDNA testing infrastructure and integration into existing treatment protocols. The work could support development of UK-based immunotherapy response monitoring strategies.
Key measures
Pretreatment variant allele frequency (VAF); on-treatment VAF; overall survival (OS); progression-free survival (PFS); objective response rate (ORR); radiologic response; molecular response metric
Outcomes reported
The study measured pretreatment and on-treatment circulating tumour DNA (ctDNA) variant allele frequencies (VAF) and their association with overall survival, progression-free survival, objective response rate, and radiologic response in patients with advanced cancers receiving immune checkpoint blockade. A 'molecular response' metric incorporating both pretreatment and on-treatment VAF was evaluated for its ability to predict long-term survival and identify responders.
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