UCL Cancer Institute, Paul O'Gorman Building, University College London, London, United Kingdom; Comprehensive Cancer Centre, School of Cancer & Pharmaceutical Sciences, King’s College London, London, United Kingdom
Rami Mustapha
Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom
Breast Cancer Now Research Unit, School of Cancer & Pharmaceutical Sciences, King’s College London, London, United Kingdom
Giovanna Alfano
Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom
Kenrick Ng
UCL Cancer Institute, Paul O'Gorman Building, University College London, London, United Kingdom
Gregory Weitsman
Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom
Luigi Dolcetti
Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom
Ali Abdulnabi Suwaidan
Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom
Felix Wong
Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom
Jose M Vicencio
UCL Cancer Institute, Paul O'Gorman Building, University College London, London, United Kingdom; Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom
Myria Galazi
UCL Cancer Institute, Paul O'Gorman Building, University College London, London, United Kingdom
UCL Cancer Institute, Paul O'Gorman Building, University College London, London, United Kingdom; Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom; Breast Cancer Now Research Unit, School of Cancer & Pharmaceutical Sciences, King’s College London, London, United Kingdom
Background: Advanced head and neck squamous cell carcinoma (HNSCC) is associated with a poor prognosis, and biomarkers that predict response to treatment are highly desirable. The primary aim was to predict progression-free survival (PFS) with a multivariate risk prediction model. Methods: Experimental covariates were derived from blood samples of 56 HNSCC patients which were prospectively obtained within a Phase 2 clinical trial (NCT02633800) at baseline and after the first treatment cycle of combined platinum-based chemotherapy with cetuximab treatment. Clinical and experimental covariates were selected by Bayesian multivariate regression to form risk scores to predict PFS. Results: A ‘baseline’ and a ‘combined’ risk prediction model were generated, each of which featuring clinical and experimental covariates. The baseline risk signature has three covariates and was strongly driven by baseline percentage of CD33+CD14+HLADRhigh monocytes. The combined signature has six covariates, also featuring baseline CD33+CD14+HLADRhigh monocytes but is strongly driven by on-treatment relative change of CD8+ central memory T cells percentages. The combined model has a higher predictive power than the baseline model and was successfully validated to predict therapeutic response in an independent cohort of nine patients from an additional Phase 2 trial (NCT03494322) assessing the addition of avelumab to cetuximab treatment in HNSCC. We identified tissue counterparts for the immune cells driving the models, using imaging mass cytometry, that specifically colocalized at the tissue level and correlated with outcome. Conclusions: This immune-based combined multimodality signature, obtained through longitudinal peripheral blood monitoring and validated in an independent cohort, presents a novel means of predicting response early on during the treatment course. Funding: Daiichi Sankyo Inc, Cancer Research UK, EU IMI2 IMMUCAN, UK Medical Research Council, European Research Council (335326), Merck Serono. Cancer Research Institute, National Institute for Health Research, Guy’s and St Thomas’ NHS Foundation Trust and The Institute of Cancer Research. Clinical trial number: NCT02633800.