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

Autor:	Barber PR; 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., Mustapha R; Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom., Flores-Borja F; Breast Cancer Now Research Unit, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom., Alfano G; Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom., Ng K; UCL Cancer Institute, Paul O'Gorman Building, University College London, London, United Kingdom., Weitsman G; Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom., Dolcetti L; Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom., Suwaidan AA; Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom., Wong F; Richard Dimbleby Laboratory of Cancer Research, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom., Vicencio JM; 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., Galazi M; UCL Cancer Institute, Paul O'Gorman Building, University College London, London, United Kingdom., Opzoomer JW; Tumor Immunology Group, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom., Arnold JN; Tumor Immunology Group, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom., Thavaraj S; Centre for Clinical, Oral & Translational Science, King's College London, London, United Kingdom., Kordasti S; Systems Cancer Immunology, School of Cancer & Pharmaceutical Sciences, King's College London, London, United Kingdom., Doyle J; Daiichi Sankyo Incorporated, Newark, United States., Greenberg J; Daiichi Sankyo Incorporated, Newark, United States., Dillon MT; The Institute of Cancer Research, London, United Kingdom., Harrington KJ; The Institute of Cancer Research, London, United Kingdom., Forster M; UCL Cancer Institute, Paul O'Gorman Building, University College London, London, United Kingdom., Coolen ACC; Institute for Mathematical and Molecular Biomedicine, King's College London, London, United Kingdom.; Saddle Point Science Ltd, London, United Kingdom., Ng T; 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.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2022 Dec 23; Vol. 11. Date of Electronic Publication: 2022 Dec 23.
DOI:	10.7554/eLife.73288
Abstrakt:	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 + HLADR high monocytes. The combined signature has six covariates, also featuring baseline CD33 + CD14 + HLADR high 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. Competing Interests: PB is a shareholder of Nano Clinical Ltd, RM, FF, GA, GW, LD, AM, FW, JV, MG, JO, JA, ST, MD No competing interests declared, KN has received honoraria from Pfizer, GSK/Tesaro and Boheringer Ingleheim, and has had travel/accommodation/expenses paid for by Tesaro, SK has received research funding in the form of a grant from Novartis and Celgene, JD, JG 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, KH 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, MF 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, AC has stock and other ownership interests with Saddle Point Science Limited, TN has received research funding from Astrazeneca and Daichii Sankyo. TN is a founder and shareholder in Nano Clinical Ltd, and PRB is a shareholder (© 2022, Barber, Mustapha, Flores-Borja et al.)
Databáze:	MEDLINE
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