On-treatment immune prognostic score for patients with relapsed and/or metastatic head and neck squamous cell carcinoma treated with immunotherapy

Background Previous studies have suggested that inflammatory markers (neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH) and fibrinogen) are prognostic biomarkers in patients with a variety of solid cancers, including those treated with immune checkpoint inhibitors (ICIs). We aimed to...

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Main Authors: Kevin Harrington, Alan Melcher, Isla Leslie, Kate Newbold, Pablo Nenclares, Lucinda Gunn, Heba Soliman, Mateo Bover, Amy Trinh, Kee Howe Wong, Chris M Nutting, Derfel ap Dafydd, Shreerang A Bhide
Format: Article
Language:English
Published: BMJ Publishing Group 2021-06-01
Series:Journal for ImmunoTherapy of Cancer
Online Access:https://jitc.bmj.com/content/9/6/e002718.full
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author Kevin Harrington
Alan Melcher
Isla Leslie
Kate Newbold
Pablo Nenclares
Lucinda Gunn
Heba Soliman
Mateo Bover
Amy Trinh
Kee Howe Wong
Chris M Nutting
Derfel ap Dafydd
Shreerang A Bhide
author_facet Kevin Harrington
Alan Melcher
Isla Leslie
Kate Newbold
Pablo Nenclares
Lucinda Gunn
Heba Soliman
Mateo Bover
Amy Trinh
Kee Howe Wong
Chris M Nutting
Derfel ap Dafydd
Shreerang A Bhide
author_sort Kevin Harrington
collection DOAJ
description Background Previous studies have suggested that inflammatory markers (neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH) and fibrinogen) are prognostic biomarkers in patients with a variety of solid cancers, including those treated with immune checkpoint inhibitors (ICIs). We aimed to develop a model that predicts response and survival in patients with relapsed and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy.Methods Analysis of 100 consecutive patients with unresectable R/M HNSCC who were treated with ICI. Baseline and on-treatment (day 28) NLR, fibrinogen and LDH were calculated and correlated with response, progression-free survival (PFS) and overall survival (OS) using univariate and multivariate analyses. The optimal cut-off values were derived using maximally selected log-rank statistics.Results Low baseline NLR and fibrinogen levels were associated with response. There was a statistically significant correlation between on-treatment NLR and fibrinogen and best overall response. On-treatment high NLR and raised fibrinogen were significantly associated with poorer outcome. In multivariate analysis, on-treatment NLR (≥4) and on-treatment fibrinogen (≥4 ng/mL) showed a significant negative correlation with OS and PFS. Using these cut-off points, we generated an on-treatment score for OS and PFS (0–2 points). The derived scoring system shows appropriate discrimination and suitability for OS (HR 2.4, 95% CI 1.7 to 3.4, p<0.0001, Harrell’s C 0.67) and PFS (HR 1.8, 95% CI 1.4 to 2.3, p<0.0001, Harrell’s C 0.68). In the absence of an external validation cohort, results of fivefold cross-validation of the score and evaluation of median OS and PFS on the Kaplan-Meier survival distribution between trained and test data exhibited appropriate accuracy and concordance of the model.Conclusions NLR and fibrinogen levels are simple, inexpensive and readily available biomarkers that could be incorporated into an on-treatment scoring system and used to help predict survival and response to ICI in patients with R/M HNSCC.
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series Journal for ImmunoTherapy of Cancer
spelling doaj-art-80225158d9a34767b69b73a1138ee17b2024-11-08T18:50:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262021-06-019610.1136/jitc-2021-002718On-treatment immune prognostic score for patients with relapsed and/or metastatic head and neck squamous cell carcinoma treated with immunotherapyKevin Harrington0Alan Melcher1Isla Leslie2Kate Newbold3Pablo Nenclares4Lucinda Gunn5Heba Soliman6Mateo Bover7Amy Trinh8Kee Howe Wong9Chris M Nutting10Derfel ap Dafydd11Shreerang A Bhide12Radiotherapy and Imaging, The Institute of Cancer Research, London, UKDivision of Radiotherapy and Imaging, The Institute of Cancer Research, London, UKHead and Neck Unit, Royal Marsden Hospital NHS Trust, London, UKHead and Neck Unit, Royal Marsden Hospital NHS Trust, London, UKHead and Neck Unit, Royal Marsden Hospital NHS Trust, London, UKHead and Neck Unit, Royal Marsden Hospital NHS Trust, London, UKHead and Neck Unit, Royal Marsden Hospital NHS Trust, London, UKHead and Neck Unit, Hospital Universitario 12 de Octubre, Madrid, SpainHead and Neck Unit, Royal Marsden Hospital NHS Trust, London, UKHead and Neck Unit, Royal Marsden Hospital NHS Trust, London, UKHead and Neck Unit, Royal Marsden Hospital NHS Trust, London, UKHead and Neck Unit, Royal Marsden Hospital NHS Trust, London, UKHead and Neck Unit, Royal Marsden Hospital NHS Trust, London, UKBackground Previous studies have suggested that inflammatory markers (neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH) and fibrinogen) are prognostic biomarkers in patients with a variety of solid cancers, including those treated with immune checkpoint inhibitors (ICIs). We aimed to develop a model that predicts response and survival in patients with relapsed and/or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy.Methods Analysis of 100 consecutive patients with unresectable R/M HNSCC who were treated with ICI. Baseline and on-treatment (day 28) NLR, fibrinogen and LDH were calculated and correlated with response, progression-free survival (PFS) and overall survival (OS) using univariate and multivariate analyses. The optimal cut-off values were derived using maximally selected log-rank statistics.Results Low baseline NLR and fibrinogen levels were associated with response. There was a statistically significant correlation between on-treatment NLR and fibrinogen and best overall response. On-treatment high NLR and raised fibrinogen were significantly associated with poorer outcome. In multivariate analysis, on-treatment NLR (≥4) and on-treatment fibrinogen (≥4 ng/mL) showed a significant negative correlation with OS and PFS. Using these cut-off points, we generated an on-treatment score for OS and PFS (0–2 points). The derived scoring system shows appropriate discrimination and suitability for OS (HR 2.4, 95% CI 1.7 to 3.4, p<0.0001, Harrell’s C 0.67) and PFS (HR 1.8, 95% CI 1.4 to 2.3, p<0.0001, Harrell’s C 0.68). In the absence of an external validation cohort, results of fivefold cross-validation of the score and evaluation of median OS and PFS on the Kaplan-Meier survival distribution between trained and test data exhibited appropriate accuracy and concordance of the model.Conclusions NLR and fibrinogen levels are simple, inexpensive and readily available biomarkers that could be incorporated into an on-treatment scoring system and used to help predict survival and response to ICI in patients with R/M HNSCC.https://jitc.bmj.com/content/9/6/e002718.full
spellingShingle Kevin Harrington
Alan Melcher
Isla Leslie
Kate Newbold
Pablo Nenclares
Lucinda Gunn
Heba Soliman
Mateo Bover
Amy Trinh
Kee Howe Wong
Chris M Nutting
Derfel ap Dafydd
Shreerang A Bhide
On-treatment immune prognostic score for patients with relapsed and/or metastatic head and neck squamous cell carcinoma treated with immunotherapy
Journal for ImmunoTherapy of Cancer
title On-treatment immune prognostic score for patients with relapsed and/or metastatic head and neck squamous cell carcinoma treated with immunotherapy
title_full On-treatment immune prognostic score for patients with relapsed and/or metastatic head and neck squamous cell carcinoma treated with immunotherapy
title_fullStr On-treatment immune prognostic score for patients with relapsed and/or metastatic head and neck squamous cell carcinoma treated with immunotherapy
title_full_unstemmed On-treatment immune prognostic score for patients with relapsed and/or metastatic head and neck squamous cell carcinoma treated with immunotherapy
title_short On-treatment immune prognostic score for patients with relapsed and/or metastatic head and neck squamous cell carcinoma treated with immunotherapy
title_sort on treatment immune prognostic score for patients with relapsed and or metastatic head and neck squamous cell carcinoma treated with immunotherapy
url https://jitc.bmj.com/content/9/6/e002718.full
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