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Discovery and Evaluation of Protein Biomarkers as a Signature of Wellness in Late-Stage Cancer Patients in Early Phase Clinical Trials

SIMPLE SUMMARY: TARGET (tumour characterisation to guide experimental targeted therapy) matches patients entering early phase cancer clinical trials to the best treatment for them based on their genetics. Selecting only fit patients for these trials means less patients need to be recruited. Fit pati...

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Autores principales: Geary, Bethany, Peat, Erin, Dransfield, Sarah, Cook, Natalie, Thistlethwaite, Fiona, Graham, Donna, Carter, Louise, Hughes, Andrew, Krebs, Matthew G., Whetton, Anthony D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157875/
https://www.ncbi.nlm.nih.gov/pubmed/34069985
http://dx.doi.org/10.3390/cancers13102443
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author Geary, Bethany
Peat, Erin
Dransfield, Sarah
Cook, Natalie
Thistlethwaite, Fiona
Graham, Donna
Carter, Louise
Hughes, Andrew
Krebs, Matthew G.
Whetton, Anthony D.
author_facet Geary, Bethany
Peat, Erin
Dransfield, Sarah
Cook, Natalie
Thistlethwaite, Fiona
Graham, Donna
Carter, Louise
Hughes, Andrew
Krebs, Matthew G.
Whetton, Anthony D.
author_sort Geary, Bethany
collection PubMed
description SIMPLE SUMMARY: TARGET (tumour characterisation to guide experimental targeted therapy) matches patients entering early phase cancer clinical trials to the best treatment for them based on their genetics. Selecting only fit patients for these trials means less patients need to be recruited. Fit patients have a life expectancy of >three months. Performance status (PS) is used to measure life expectancy and is decided by doctors asking questions about patient’s activity levels. We created a Wellness Score using proteins in 55 patient’s blood samples. This score groups patients into those who were likely to die and those who were likely to be alive within six months of their blood sample. This score was more accurately able to predict a patient’s survival at six months than PS. We then reached the same conclusion in a further 77 patients. We hope this score can now be tested in an even larger group of patients. ABSTRACT: TARGET (tumour characterisation to guide experimental targeted therapy) is a cancer precision medicine programme focused on molecular characterisation of patients entering early phase clinical trials. Performance status (PS) measures a patient’s ability to perform a variety of activities. However, the quality of present algorithms to assess PS is limited and based on qualitative clinician assessment. Plasma samples from patients enrolled into TARGET were analysed using the mass spectrometry (MS) technique: sequential window acquisition of all theoretical fragment ion spectra (SWATH)-MS. SWATH-MS was used on a discovery cohort of 55 patients to differentiate patients into either a good or poor prognosis by creation of a Wellness Score (WS) that showed stronger prediction of overall survival (p = 0.000551) compared to PS (p = 0.001). WS was then tested against a validation cohort of 77 patients showing significant (p = 0.000451) prediction of overall survival. WS in both sets had receiver operating characteristic curve area under the curve (AUC) values of 0.76 (p = 0.002) and 0.67 (p = 0.011): AUC of PS was 0.70 (p = 0.117) and 0.55 (p = 0.548). These signatures can now be evaluated further in larger patient populations to assess their utility in a clinical setting.
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spelling pubmed-81578752021-05-28 Discovery and Evaluation of Protein Biomarkers as a Signature of Wellness in Late-Stage Cancer Patients in Early Phase Clinical Trials Geary, Bethany Peat, Erin Dransfield, Sarah Cook, Natalie Thistlethwaite, Fiona Graham, Donna Carter, Louise Hughes, Andrew Krebs, Matthew G. Whetton, Anthony D. Cancers (Basel) Article SIMPLE SUMMARY: TARGET (tumour characterisation to guide experimental targeted therapy) matches patients entering early phase cancer clinical trials to the best treatment for them based on their genetics. Selecting only fit patients for these trials means less patients need to be recruited. Fit patients have a life expectancy of >three months. Performance status (PS) is used to measure life expectancy and is decided by doctors asking questions about patient’s activity levels. We created a Wellness Score using proteins in 55 patient’s blood samples. This score groups patients into those who were likely to die and those who were likely to be alive within six months of their blood sample. This score was more accurately able to predict a patient’s survival at six months than PS. We then reached the same conclusion in a further 77 patients. We hope this score can now be tested in an even larger group of patients. ABSTRACT: TARGET (tumour characterisation to guide experimental targeted therapy) is a cancer precision medicine programme focused on molecular characterisation of patients entering early phase clinical trials. Performance status (PS) measures a patient’s ability to perform a variety of activities. However, the quality of present algorithms to assess PS is limited and based on qualitative clinician assessment. Plasma samples from patients enrolled into TARGET were analysed using the mass spectrometry (MS) technique: sequential window acquisition of all theoretical fragment ion spectra (SWATH)-MS. SWATH-MS was used on a discovery cohort of 55 patients to differentiate patients into either a good or poor prognosis by creation of a Wellness Score (WS) that showed stronger prediction of overall survival (p = 0.000551) compared to PS (p = 0.001). WS was then tested against a validation cohort of 77 patients showing significant (p = 0.000451) prediction of overall survival. WS in both sets had receiver operating characteristic curve area under the curve (AUC) values of 0.76 (p = 0.002) and 0.67 (p = 0.011): AUC of PS was 0.70 (p = 0.117) and 0.55 (p = 0.548). These signatures can now be evaluated further in larger patient populations to assess their utility in a clinical setting. MDPI 2021-05-18 /pmc/articles/PMC8157875/ /pubmed/34069985 http://dx.doi.org/10.3390/cancers13102443 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Geary, Bethany
Peat, Erin
Dransfield, Sarah
Cook, Natalie
Thistlethwaite, Fiona
Graham, Donna
Carter, Louise
Hughes, Andrew
Krebs, Matthew G.
Whetton, Anthony D.
Discovery and Evaluation of Protein Biomarkers as a Signature of Wellness in Late-Stage Cancer Patients in Early Phase Clinical Trials
title Discovery and Evaluation of Protein Biomarkers as a Signature of Wellness in Late-Stage Cancer Patients in Early Phase Clinical Trials
title_full Discovery and Evaluation of Protein Biomarkers as a Signature of Wellness in Late-Stage Cancer Patients in Early Phase Clinical Trials
title_fullStr Discovery and Evaluation of Protein Biomarkers as a Signature of Wellness in Late-Stage Cancer Patients in Early Phase Clinical Trials
title_full_unstemmed Discovery and Evaluation of Protein Biomarkers as a Signature of Wellness in Late-Stage Cancer Patients in Early Phase Clinical Trials
title_short Discovery and Evaluation of Protein Biomarkers as a Signature of Wellness in Late-Stage Cancer Patients in Early Phase Clinical Trials
title_sort discovery and evaluation of protein biomarkers as a signature of wellness in late-stage cancer patients in early phase clinical trials
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8157875/
https://www.ncbi.nlm.nih.gov/pubmed/34069985
http://dx.doi.org/10.3390/cancers13102443
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