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dc.contributor.authorBarber, PR
dc.contributor.authorMustapha, R
dc.contributor.authorFlores-Borja, F
dc.contributor.authorAlfano, G
dc.contributor.authorNg, K
dc.contributor.authorWeitsman, G
dc.contributor.authorDolcetti, L
dc.contributor.authorSuwaidan, AA
dc.contributor.authorWong, F
dc.contributor.authorVicencio, JM
dc.contributor.authorGalazi, M
dc.contributor.authorOpzoomer, JW
dc.contributor.authorArnold, JN
dc.contributor.authorThavaraj, S
dc.contributor.authorKordasti, S
dc.contributor.authorDoyle, J
dc.contributor.authorGreenberg, J
dc.contributor.authorDillon, MT
dc.contributor.authorHarrington, KJ
dc.contributor.authorForster, M
dc.contributor.authorCoolen, ACC
dc.contributor.authorNg, T
dc.coverage.spatialEngland
dc.date.accessioned2023-03-10T15:49:27Z
dc.date.available2023-03-10T15:49:27Z
dc.date.issued2022-12-23
dc.identifierARTN e73288
dc.identifier73288
dc.identifier.citationeLife, 2022, 11 pp. e73288 -
dc.identifier.issn2050-084X
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/5723
dc.identifier.eissn2050-084X
dc.identifier.eissn2050-084X
dc.identifier.doi10.7554/eLife.73288
dc.description.abstractBACKGROUND: 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.
dc.formatElectronic
dc.format.extente73288 -
dc.languageeng
dc.language.isoeng
dc.publishereLIFE SCIENCES PUBL LTD
dc.relation.ispartofeLife
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.subjectcancer biology
dc.subjectclinical trial
dc.subjectcomputational biology
dc.subjecthead
dc.subjecthuman
dc.subjectmachine learning
dc.subjectmonocytes
dc.subjectneck cancer
dc.subjectpredictive signature
dc.subjectsystems biology
dc.subjectHumans
dc.subjectSquamous Cell Carcinoma of Head and Neck
dc.subjectCetuximab
dc.subjectProgression-Free Survival
dc.subjectBayes Theorem
dc.subjectHead and Neck Neoplasms
dc.titlePredicting progression-free survival after systemic therapy in advanced head and neck cancer: Bayesian regression and model development.
dc.typeJournal Article
dcterms.dateAccepted2022-12-22
dc.date.updated2023-03-10T15:48:44Z
rioxxterms.versionVoR
rioxxterms.versionofrecord10.7554/eLife.73288
rioxxterms.licenseref.startdate2022-12-23
rioxxterms.typeJournal Article/Review
pubs.author-urlhttps://www.ncbi.nlm.nih.gov/pubmed/36562609
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Biology/Targeted Therapy
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Targeted Therapy
pubs.organisational-group/ICR/Students
pubs.organisational-group/ICR/Students/PhD and MPhil
pubs.organisational-group/ICR/Students/PhD and MPhil/14/15 Starting Cohort
pubs.publication-statusPublished online
pubs.publisher-urlhttp://dx.doi.org/10.7554/elife.73288
pubs.volume11
icr.researchteamTargeted Therapy
dc.contributor.icrauthorDillon, Magnus
dc.contributor.icrauthorHarrington, Kevin
icr.provenanceDeposited by Mr Arek Surman on 2023-03-10. Deposit type is initial. No. of files: 1. Files: Predicting progression-free survival after systemic therapy in advanced head and neck cancer Bayesian regression and model d.pdf


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