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Predicting Progression Free Survival after Systemic Therapy in Advanced Head and Neck Cancer: Bayesian regression and Model development

Research output: Contribution to journalArticlepeer-review

Paul R Barber, Rami Mustapha, Fabian Flores-Borja, Giovanna Alfano, Kenrick Ng, Gregory Weitsman, Luigi Dolcetti, Ali Mohamed, Felix Wong, Jose Vicencio Bustamante, Myria Galazi, Jamie Opzoomer, James Arnold, Selvam Thavaraj, Shahram Kordasti, Jana Doyle, Jon Greenberg, Magnus Dillon, Kevin J Harrington, Martin Forster & 2 more Anthony CC Coolen, Tony Ng

Original languageEnglish
JournaleLife
VolumeIn press
Early online date23 Dec 2022
DOIs
Accepted/In press22 Dec 2022
E-pub ahead of print23 Dec 2022

King's Authors

Abstract

Background: Advanced Head and Neck Squamous Cell Cancer (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 Progression Free Survival (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 3 covariates and was strongly driven by baseline percentage of CD33+CD14+HLADRhigh monocytes. The combined signature has 6 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 9 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.

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