Journal Article

Predicting progression-free survival after systemic therapy in advanced head and neck cancer: Bayesian regression and model development

Thavaraj, Selvam, Opzoomer, James W, Alfano, Giovanna, Harrington, Kevin J, Dillon, Magnus T, Kordasti, Shahram, Ng, Tony, Mustapha, Rami, Weitsman, Gregory, Arnold, James N, Barber, Paul R, Suwaidan, Ali Abdulnabi, Vicencio, Jose M, Greenberg, Jon, Coolen, Anthony CC, Ng, Kenrick, Dolcetti, Luigi, Forster, Martin, Flores-Borja, Fabian, Doyle, Jana, Galazi, Myria, Wong, Felix

2022

Overview

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. 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. 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 HLADR monocytes. The combined signature has six covariates, also featuring baseline CD33 CD14 HLADR 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. 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. 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. NCT02633800.

• Publisher: eLife Sciences Publications Ltd,eLife Sciences Publications, Ltd
• Subject: Antibodies / Bayes Theorem / Bayesian analysis / Biomarkers / Biopsy / Cancer Biology / Cancer research / CD14 antigen / CD8 antigen / Cell culture / Cetuximab - therapeutic use / Chemotherapy / clinical trial / Clinical trials / Computational and Systems Biology / Cytometry / Flow cytometry / Gene expression / head / Head & neck cancer / Head and neck carcinoma / Head and Neck Neoplasms - drug therapy / Humans / Immunological memory / Immunotherapy / Laboratories / Lymphocytes T / Machine learning / Mathematical models / Medical prognosis / Medical research / Memory cells / MicroRNAs / Monoclonal antibodies / Monocytes / Multivariate analysis / neck cancer / Patients / Peripheral blood / Prediction models / predictive signature / Progression-Free Survival / Research ethics / Squamous cell carcinoma / Squamous Cell Carcinoma of Head and Neck - drug therapy / Targeted cancer therapy