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

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.

Data availability

The data generated in this study and used for multivariate modelling are available from the UCL repository: https://doi.org/10.5522/04/16566207.v1

The following data sets were generated

Article and author information

Author details

  1. Paul R Barber

    UCL Cancer Institute, University College London, London, United Kingdom
    Competing interests
    Paul R Barber, is a shareholder of Nano Clinical Ltd.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8595-1141
  2. Rami Mustapha

    Richard Dimbleby Laboratory of Cancer Research, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  3. Fabian Flores-Borja

    Breast Cancer Now Research Unit, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0881-8822
  4. Giovanna Alfano

    Richard Dimbleby Laboratory of Cancer Research, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  5. Kenrick Ng

    UCL Cancer Institute, University College London, London, United Kingdom
    Competing interests
    Kenrick Ng, has received honoraria from Pfizer, GSK/Tesaro and Boheringer Ingleheim, and has had travel/accommodation/expenses paid for by Tesaro..
  6. Gregory Weitsman

    Richard Dimbleby Laboratory of Cancer Research, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  7. Luigi Dolcetti

    Richard Dimbleby Laboratory of Cancer Research, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  8. Ali Abdulnabi Suwaidan

    Richard Dimbleby Laboratory of Cancer Research, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  9. Felix Wong

    Richard Dimbleby Laboratory of Cancer Research, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  10. Jose M Vicencio

    UCL Cancer Institute, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  11. Myria Galazi

    UCL Cancer Institute, University College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  12. James W Opzoomer

    Tumor Immunology Group, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6842-756X
  13. James N Arnold

    Tumor Immunology Group, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
  14. Selvam Thavaraj

    Centre for Oral, Clinical and Translational Sciences, King's College London, London, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5720-7422
  15. Shahram Kordasti

    Systems Cancer Immunology, King's College London, London, United Kingdom
    Competing interests
    Shahram Kordasti, has received research funding in the form of a grant from Novartis and Celgene.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0347-4207
  16. Jana Doyle

    Daichii Sankyo Incorporated, New Jersey, United States
    Competing interests
    Jana Doyle, is in employment with Daichii Sankyo, and has stock and other ownership interests, research funding within Daichii Sankyo and has had travel/accommodation/expenses paid for by Daichii Sankyo.
  17. Jon Greenberg

    Daichii Sankyo Incorporated, New Jersey, United States
    Competing interests
    Jon Greenberg, is in employment with Daichii Sankyo, and has stock and other ownership interests, research funding within Daichii Sankyo and has had travel/accommodation/expenses paid for by Daichii Sankyo.
  18. Magnus T Dillon

    Institute of Cancer Research, London, United Kingdom
    Competing interests
    No competing interests declared.
  19. Kevin J Harrington

    Institute of Cancer Research, London, United Kingdom
    Competing interests
    Kevin J Harrington, has received honoraria from Amgen; Arch Oncology; AstraZeneca; Boehringer-Ingelheim; Bristol-Myers Squibb; Codiak; Inzen; Merck; MSD; Pfizer; Replimune and is on a speakers' bureau for Amgen, AstraZeneca; Bristol-Myers Squibb; Merck, MSD; Pfizer. KH has also received research funding from AstraZeneca, Boehringer-Ingelheim, MSD and Replimune..
  20. Martin D Forster

    UCL Cancer Institute, University College London, London, United Kingdom
    Competing interests
    Martin D Forster, has received institutional research funding from AstraZeneca, Boehringer-Ingelheim, Merck and MSD and serves in a consulting or advisory role to Achilles, Astrazeneca, Bayer, Bristol-Myers Squibb, Celgene, Guardant Health, Merck, MSD, Nanobiotix, Novartis, Oxford VacMedix, Pfizer, Roche, Takeda, UltraHuman.
  21. Anthony C C Coolen

    Institute for Mathematical and Molecular Biomedicine, King's College London, London, United Kingdom
    Competing interests
    Anthony C C Coolen, has stock and other ownership interests with Saddle Point Science Limited..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6976-5875
  22. Tony Ng

    Breast Cancer Now Research Unit, King's College London, London, United Kingdom
    For correspondence
    tony.ng@kcl.ac.uk
    Competing interests
    Tony Ng, has received research funding from Astrazeneca and Daichii Sankyo. TN is a founder and shareholder in Nano Clinical Ltd, and PRB is a shareholder..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-3894-5619

Funding

Cancer Research UK (Early Detection Award C7675/A29313)

  • Paul R Barber

Institute of Cancer Research

  • Magnus T Dillon
  • Kevin J Harrington

Guy's and St Thomas' NHS Foundation Trust

  • Selvam Thavaraj

Cancer Research UK

  • Rami Mustapha
  • Gregory Weitsman
  • Shahram Kordasti

Cancer Research UK (City of London Centre CTRQQR-2021\100004)

  • Paul R Barber
  • Tony Ng

Cancer Research UK (Clinical Fellowship Awards)

  • Kenrick Ng
  • Ali Abdulnabi Suwaidan
  • Myria Galazi

Cancer Research UK (Early Detection and Diagnosis Committee Project grant)

  • Giovanna Alfano
  • Jose M Vicencio

Innovative Health Initiative (EU IMI2 IMMUCAN (Grant agreement number 821558))

  • Luigi Dolcetti

Medical Research Council (MR/N013700/1)

  • James W Opzoomer

Medical Research Council (MR/N013700/1)

  • Felix Wong

Cancer Research UK (DCRPGF\100009)

  • James N Arnold

Cancer Research Institute (Wade F.B. Thompson CLIP grant (CRI3645))

  • James N Arnold

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Jennifer Grandis, University of California, San Francisco, United States

Ethics

Human subjects: Written informed consent was obtained for all patients who participated in the Phase 2 clinical trial. Approval was obtained from ethics committees (Research Ethics Committee reference: 15/LO/1670). Approval to procure and process a separate cohort of blood samples from patients at risk of developing lung cancer was also obtained (IRAS ID: 261766).

Version history

  1. Received: August 24, 2021
  2. Preprint posted: September 23, 2021 (view preprint)
  3. Accepted: December 22, 2022
  4. Accepted Manuscript published: December 23, 2022 (version 1)
  5. Version of Record published: January 5, 2023 (version 2)

Copyright

© 2022, Barber et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Paul R Barber
  2. Rami Mustapha
  3. Fabian Flores-Borja
  4. Giovanna Alfano
  5. Kenrick Ng
  6. Gregory Weitsman
  7. Luigi Dolcetti
  8. Ali Abdulnabi Suwaidan
  9. Felix Wong
  10. Jose M Vicencio
  11. Myria Galazi
  12. James W Opzoomer
  13. James N Arnold
  14. Selvam Thavaraj
  15. Shahram Kordasti
  16. Jana Doyle
  17. Jon Greenberg
  18. Magnus T Dillon
  19. Kevin J Harrington
  20. Martin D Forster
  21. Anthony C C Coolen
  22. Tony Ng
(2022)
Predicting progression free survival after systemic therapy in advanced head and neck cancer: Bayesian regression and model development
eLife 11:e73288.
https://doi.org/10.7554/eLife.73288

Share this article

https://doi.org/10.7554/eLife.73288

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