Cargando…

Cell Death, Inflammation, Tumor Burden, and Proliferation Blood Biomarkers Predict Lung Cancer Radiotherapy Response and Correlate With Tumor Volume and Proliferation Imaging

INTRODUCTION: There is an unmet need to develop noninvasive biomarkers to stratify patients in drug-radiotherapy trials. In this pilot study we investigated lung cancer radiotherapy response and toxicity blood biomarkers and correlated findings with tumor volume and proliferation imaging. PATIENTS A...

Descripción completa

Detalles Bibliográficos
Autores principales: Salem, Ahmed, Mistry, Hitesh, Backen, Alison, Hodgson, Clare, Koh, Pek, Dean, Emma, Priest, Lynsey, Haslett, Kate, Trigonis, Ioannis, Jackson, Alan, Asselin, Marie-Claude, Dive, Caroline, Renehan, Andrew, Faivre-Finn, Corinne, Blackhall, Fiona
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927801/
https://www.ncbi.nlm.nih.gov/pubmed/29398577
http://dx.doi.org/10.1016/j.cllc.2017.12.002
_version_ 1783319124508672000
author Salem, Ahmed
Mistry, Hitesh
Backen, Alison
Hodgson, Clare
Koh, Pek
Dean, Emma
Priest, Lynsey
Haslett, Kate
Trigonis, Ioannis
Jackson, Alan
Asselin, Marie-Claude
Dive, Caroline
Renehan, Andrew
Faivre-Finn, Corinne
Blackhall, Fiona
author_facet Salem, Ahmed
Mistry, Hitesh
Backen, Alison
Hodgson, Clare
Koh, Pek
Dean, Emma
Priest, Lynsey
Haslett, Kate
Trigonis, Ioannis
Jackson, Alan
Asselin, Marie-Claude
Dive, Caroline
Renehan, Andrew
Faivre-Finn, Corinne
Blackhall, Fiona
author_sort Salem, Ahmed
collection PubMed
description INTRODUCTION: There is an unmet need to develop noninvasive biomarkers to stratify patients in drug-radiotherapy trials. In this pilot study we investigated lung cancer radiotherapy response and toxicity blood biomarkers and correlated findings with tumor volume and proliferation imaging. PATIENTS AND METHODS: Blood samples were collected before and during (day 21) radiotherapy. Twenty-six cell-death, hypoxia, angiogenesis, inflammation, proliferation, invasion, and tumor-burden biomarkers were evaluated. Clinical and laboratory data were collected. Univariate analysis was performed on small-cell and non–small-cell lung cancer (NSCLC) whereas multivariate analysis focused on NSCLC. RESULTS: Blood samples from 78 patients were analyzed. Sixty-one (78.2%) harbored NSCLC, 48 (61.5%) received sequential chemoradiotherapy. Of tested baseline biomarkers, undetectable interleukin (IL)-1b (hazard ratio [HR], 4.02; 95% confidence interval [CI], 2.04-7.93; P < .001) was the only significant survival covariate. Of routinely collected laboratory tests, high baseline neutrophil count was a significant survival covariate (HR, 1.07; 95% CI, 1.02-1.11; P = .017). Baseline IL-1b and neutrophil count were prognostic for survival in a multivariate model. The addition of day-21 cytokeratin-19 antigen modestly improved this model's survival prediction (concordance probability, 0.75-0.78). Chemotherapy (P < .001) and baseline keratinocyte growth factor (P = .019) predicted acute esophagitis, but only chemotherapy remained significant after Bonferroni correction. Baseline angioprotein-1 and hepatocyte growth factor showed a direct correlation with tumor volume whereas changes in vascular cell adhesion molecule 1 showed significant correlations with 18F-fluorothymidine (FLT) positron emission tomography (PET). CONCLUSION: Select biomarkers are prognostic after radiotherapy in this lung cancer series. The correlation between circulating biomarkers and 18F-FLT PET is shown, to our knowledge for the first time, highlighting their potential role as imaging surrogates.
format Online
Article
Text
id pubmed-5927801
institution National Center for Biotechnology Information
language English
publishDate 2018
publisher Elsevier
record_format MEDLINE/PubMed
spelling pubmed-59278012018-05-01 Cell Death, Inflammation, Tumor Burden, and Proliferation Blood Biomarkers Predict Lung Cancer Radiotherapy Response and Correlate With Tumor Volume and Proliferation Imaging Salem, Ahmed Mistry, Hitesh Backen, Alison Hodgson, Clare Koh, Pek Dean, Emma Priest, Lynsey Haslett, Kate Trigonis, Ioannis Jackson, Alan Asselin, Marie-Claude Dive, Caroline Renehan, Andrew Faivre-Finn, Corinne Blackhall, Fiona Clin Lung Cancer Article INTRODUCTION: There is an unmet need to develop noninvasive biomarkers to stratify patients in drug-radiotherapy trials. In this pilot study we investigated lung cancer radiotherapy response and toxicity blood biomarkers and correlated findings with tumor volume and proliferation imaging. PATIENTS AND METHODS: Blood samples were collected before and during (day 21) radiotherapy. Twenty-six cell-death, hypoxia, angiogenesis, inflammation, proliferation, invasion, and tumor-burden biomarkers were evaluated. Clinical and laboratory data were collected. Univariate analysis was performed on small-cell and non–small-cell lung cancer (NSCLC) whereas multivariate analysis focused on NSCLC. RESULTS: Blood samples from 78 patients were analyzed. Sixty-one (78.2%) harbored NSCLC, 48 (61.5%) received sequential chemoradiotherapy. Of tested baseline biomarkers, undetectable interleukin (IL)-1b (hazard ratio [HR], 4.02; 95% confidence interval [CI], 2.04-7.93; P < .001) was the only significant survival covariate. Of routinely collected laboratory tests, high baseline neutrophil count was a significant survival covariate (HR, 1.07; 95% CI, 1.02-1.11; P = .017). Baseline IL-1b and neutrophil count were prognostic for survival in a multivariate model. The addition of day-21 cytokeratin-19 antigen modestly improved this model's survival prediction (concordance probability, 0.75-0.78). Chemotherapy (P < .001) and baseline keratinocyte growth factor (P = .019) predicted acute esophagitis, but only chemotherapy remained significant after Bonferroni correction. Baseline angioprotein-1 and hepatocyte growth factor showed a direct correlation with tumor volume whereas changes in vascular cell adhesion molecule 1 showed significant correlations with 18F-fluorothymidine (FLT) positron emission tomography (PET). CONCLUSION: Select biomarkers are prognostic after radiotherapy in this lung cancer series. The correlation between circulating biomarkers and 18F-FLT PET is shown, to our knowledge for the first time, highlighting their potential role as imaging surrogates. Elsevier 2018-05 /pmc/articles/PMC5927801/ /pubmed/29398577 http://dx.doi.org/10.1016/j.cllc.2017.12.002 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Salem, Ahmed
Mistry, Hitesh
Backen, Alison
Hodgson, Clare
Koh, Pek
Dean, Emma
Priest, Lynsey
Haslett, Kate
Trigonis, Ioannis
Jackson, Alan
Asselin, Marie-Claude
Dive, Caroline
Renehan, Andrew
Faivre-Finn, Corinne
Blackhall, Fiona
Cell Death, Inflammation, Tumor Burden, and Proliferation Blood Biomarkers Predict Lung Cancer Radiotherapy Response and Correlate With Tumor Volume and Proliferation Imaging
title Cell Death, Inflammation, Tumor Burden, and Proliferation Blood Biomarkers Predict Lung Cancer Radiotherapy Response and Correlate With Tumor Volume and Proliferation Imaging
title_full Cell Death, Inflammation, Tumor Burden, and Proliferation Blood Biomarkers Predict Lung Cancer Radiotherapy Response and Correlate With Tumor Volume and Proliferation Imaging
title_fullStr Cell Death, Inflammation, Tumor Burden, and Proliferation Blood Biomarkers Predict Lung Cancer Radiotherapy Response and Correlate With Tumor Volume and Proliferation Imaging
title_full_unstemmed Cell Death, Inflammation, Tumor Burden, and Proliferation Blood Biomarkers Predict Lung Cancer Radiotherapy Response and Correlate With Tumor Volume and Proliferation Imaging
title_short Cell Death, Inflammation, Tumor Burden, and Proliferation Blood Biomarkers Predict Lung Cancer Radiotherapy Response and Correlate With Tumor Volume and Proliferation Imaging
title_sort cell death, inflammation, tumor burden, and proliferation blood biomarkers predict lung cancer radiotherapy response and correlate with tumor volume and proliferation imaging
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5927801/
https://www.ncbi.nlm.nih.gov/pubmed/29398577
http://dx.doi.org/10.1016/j.cllc.2017.12.002
work_keys_str_mv AT salemahmed celldeathinflammationtumorburdenandproliferationbloodbiomarkerspredictlungcancerradiotherapyresponseandcorrelatewithtumorvolumeandproliferationimaging
AT mistryhitesh celldeathinflammationtumorburdenandproliferationbloodbiomarkerspredictlungcancerradiotherapyresponseandcorrelatewithtumorvolumeandproliferationimaging
AT backenalison celldeathinflammationtumorburdenandproliferationbloodbiomarkerspredictlungcancerradiotherapyresponseandcorrelatewithtumorvolumeandproliferationimaging
AT hodgsonclare celldeathinflammationtumorburdenandproliferationbloodbiomarkerspredictlungcancerradiotherapyresponseandcorrelatewithtumorvolumeandproliferationimaging
AT kohpek celldeathinflammationtumorburdenandproliferationbloodbiomarkerspredictlungcancerradiotherapyresponseandcorrelatewithtumorvolumeandproliferationimaging
AT deanemma celldeathinflammationtumorburdenandproliferationbloodbiomarkerspredictlungcancerradiotherapyresponseandcorrelatewithtumorvolumeandproliferationimaging
AT priestlynsey celldeathinflammationtumorburdenandproliferationbloodbiomarkerspredictlungcancerradiotherapyresponseandcorrelatewithtumorvolumeandproliferationimaging
AT haslettkate celldeathinflammationtumorburdenandproliferationbloodbiomarkerspredictlungcancerradiotherapyresponseandcorrelatewithtumorvolumeandproliferationimaging
AT trigonisioannis celldeathinflammationtumorburdenandproliferationbloodbiomarkerspredictlungcancerradiotherapyresponseandcorrelatewithtumorvolumeandproliferationimaging
AT jacksonalan celldeathinflammationtumorburdenandproliferationbloodbiomarkerspredictlungcancerradiotherapyresponseandcorrelatewithtumorvolumeandproliferationimaging
AT asselinmarieclaude celldeathinflammationtumorburdenandproliferationbloodbiomarkerspredictlungcancerradiotherapyresponseandcorrelatewithtumorvolumeandproliferationimaging
AT divecaroline celldeathinflammationtumorburdenandproliferationbloodbiomarkerspredictlungcancerradiotherapyresponseandcorrelatewithtumorvolumeandproliferationimaging
AT renehanandrew celldeathinflammationtumorburdenandproliferationbloodbiomarkerspredictlungcancerradiotherapyresponseandcorrelatewithtumorvolumeandproliferationimaging
AT faivrefinncorinne celldeathinflammationtumorburdenandproliferationbloodbiomarkerspredictlungcancerradiotherapyresponseandcorrelatewithtumorvolumeandproliferationimaging
AT blackhallfiona celldeathinflammationtumorburdenandproliferationbloodbiomarkerspredictlungcancerradiotherapyresponseandcorrelatewithtumorvolumeandproliferationimaging