Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN)

Emelie Gezelius; Pär Ola Bendahl; Widet Gallo; Kelin Gonçalves de Oliveira; Lars Ek; Bengt Bergman; Jan Sundberg; Olle Melander; Mattias Belting

doi:10.3390/cancers14051307

Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN)

Emelie Gezelius, Pär Ola Bendahl, Widet Gallo, Kelin Gonçalves de Oliveira, Lars Ek, Bengt Bergman, Jan Sundberg, Olle Melander, Mattias Belting

Research output: Contribution to journal › Article › peer-review

Abstract

Cardiovascular comorbidity is common in small cell lung cancer (SCLC) and may significantly affect treatment tolerability and patient outcome. Still, there are no established biomarkers for objective and dynamic assessment as a tool for improved treatment decisions. We have investigated circulating levels of midregional-pro-adrenomedullin (MR-proADM), midregional-proatrial-natriuretic peptide (MR-proANP), copeptin (surrogate for vasopressin) and suppression-of-tumorigenicity-2 (ST2), all known to correlate with various aspects of cardiovascular function, in a SCLC cohort (N = 252) from a randomized, controlled trial (RASTEN). For all measured biomarkers, protein levels were inversely associated with survival, particularly with ST2 and MR-proADM, where the top versus bottom quartile was associated with an adjusted hazard ratio of 2.40 (95% CI 1.44–3.98; p = 0.001) and 2.18 (95% CI 1.35–3.51; p = 0.001), respectively, in the entire cohort, and 3.43 (95% CI 1.73–6.79; p < 0.001) and 3.49 (95% CI 1.84–6.60; p < 0.001), respectively, in extensive disease patients. A high combined score of MR-proADM and ST2 was associated with a significantly reduced median OS of 7.0 months vs. 14.9 months for patients with a low combined score. We conclude that the cardiovascular biomarkers MR-proADM and ST2 strongly correlate with survival in SCLC, warranting prospective studies on the clinical utility of MR-proADM and ST2 for improved, individualized treatment decisions.

Original language	English
Article number	1307
Pages (from-to)	1-14
Journal	Cancers
Volume	14
Issue number	5
DOIs	https://doi.org/10.3390/cancers14051307
Publication status	Published - 2022

Subject classification (UKÄ)

Cancer and Oncology

Free keywords

Cardiovascular biomarkers
Individualized treatment
Small cell lung cancer

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers14051307Licence: CC BY

1 Doctoral Thesis (compilation)

Coagulation and other aspects of the cardiovascular system in small cell lung cancer
Gezelius, E., 2022, Lund: Lund University, Faculty of Medicine. 102 p.
Research output: Thesis › Doctoral Thesis (compilation)

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@article{b397576dab21465d852026a2be4de1ab,

title = "Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN)",

abstract = "Cardiovascular comorbidity is common in small cell lung cancer (SCLC) and may significantly affect treatment tolerability and patient outcome. Still, there are no established biomarkers for objective and dynamic assessment as a tool for improved treatment decisions. We have investigated circulating levels of midregional-pro-adrenomedullin (MR-proADM), midregional-proatrial-natriuretic peptide (MR-proANP), copeptin (surrogate for vasopressin) and suppression-of-tumorigenicity-2 (ST2), all known to correlate with various aspects of cardiovascular function, in a SCLC cohort (N = 252) from a randomized, controlled trial (RASTEN). For all measured biomarkers, protein levels were inversely associated with survival, particularly with ST2 and MR-proADM, where the top versus bottom quartile was associated with an adjusted hazard ratio of 2.40 (95% CI 1.44–3.98; p = 0.001) and 2.18 (95% CI 1.35–3.51; p = 0.001), respectively, in the entire cohort, and 3.43 (95% CI 1.73–6.79; p < 0.001) and 3.49 (95% CI 1.84–6.60; p < 0.001), respectively, in extensive disease patients. A high combined score of MR-proADM and ST2 was associated with a significantly reduced median OS of 7.0 months vs. 14.9 months for patients with a low combined score. We conclude that the cardiovascular biomarkers MR-proADM and ST2 strongly correlate with survival in SCLC, warranting prospective studies on the clinical utility of MR-proADM and ST2 for improved, individualized treatment decisions.",

keywords = "Cardiovascular biomarkers, Individualized treatment, Small cell lung cancer",

author = "Emelie Gezelius and Bendahl, {P{\"a}r Ola} and Widet Gallo and {de Oliveira}, {Kelin Gon{\c c}alves} and Lars Ek and Bengt Bergman and Jan Sundberg and Olle Melander and Mattias Belting",

note = "Funding Information: This study was funded by grants from the Swedish Cancer Fund CAN 2017/664 (M.B.); the Swedish Research Council VR-MH 2018-02562 (M.B.); the Fru Berta Kamprad Foundation (M.B.); the Sk?ne University Hospital donation funds (M.B.); and the Governmental funding of clinical research within the national health services, ALF (E.G. and M.B.). Publisher Copyright: {\textcopyright} 2022 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2022",

doi = "10.3390/cancers14051307",

language = "English",

volume = "14",

pages = "1--14",

journal = "Cancers",

issn = "2072-6694",

publisher = "MDPI AG",

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TY - JOUR

T1 - Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN)

AU - Gezelius, Emelie

AU - Bendahl, Pär Ola

AU - Gallo, Widet

AU - de Oliveira, Kelin Gonçalves

AU - Ek, Lars

AU - Bergman, Bengt

AU - Sundberg, Jan

AU - Melander, Olle

AU - Belting, Mattias

N1 - Funding Information: This study was funded by grants from the Swedish Cancer Fund CAN 2017/664 (M.B.); the Swedish Research Council VR-MH 2018-02562 (M.B.); the Fru Berta Kamprad Foundation (M.B.); the Sk?ne University Hospital donation funds (M.B.); and the Governmental funding of clinical research within the national health services, ALF (E.G. and M.B.). Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2022

Y1 - 2022

N2 - Cardiovascular comorbidity is common in small cell lung cancer (SCLC) and may significantly affect treatment tolerability and patient outcome. Still, there are no established biomarkers for objective and dynamic assessment as a tool for improved treatment decisions. We have investigated circulating levels of midregional-pro-adrenomedullin (MR-proADM), midregional-proatrial-natriuretic peptide (MR-proANP), copeptin (surrogate for vasopressin) and suppression-of-tumorigenicity-2 (ST2), all known to correlate with various aspects of cardiovascular function, in a SCLC cohort (N = 252) from a randomized, controlled trial (RASTEN). For all measured biomarkers, protein levels were inversely associated with survival, particularly with ST2 and MR-proADM, where the top versus bottom quartile was associated with an adjusted hazard ratio of 2.40 (95% CI 1.44–3.98; p = 0.001) and 2.18 (95% CI 1.35–3.51; p = 0.001), respectively, in the entire cohort, and 3.43 (95% CI 1.73–6.79; p < 0.001) and 3.49 (95% CI 1.84–6.60; p < 0.001), respectively, in extensive disease patients. A high combined score of MR-proADM and ST2 was associated with a significantly reduced median OS of 7.0 months vs. 14.9 months for patients with a low combined score. We conclude that the cardiovascular biomarkers MR-proADM and ST2 strongly correlate with survival in SCLC, warranting prospective studies on the clinical utility of MR-proADM and ST2 for improved, individualized treatment decisions.

AB - Cardiovascular comorbidity is common in small cell lung cancer (SCLC) and may significantly affect treatment tolerability and patient outcome. Still, there are no established biomarkers for objective and dynamic assessment as a tool for improved treatment decisions. We have investigated circulating levels of midregional-pro-adrenomedullin (MR-proADM), midregional-proatrial-natriuretic peptide (MR-proANP), copeptin (surrogate for vasopressin) and suppression-of-tumorigenicity-2 (ST2), all known to correlate with various aspects of cardiovascular function, in a SCLC cohort (N = 252) from a randomized, controlled trial (RASTEN). For all measured biomarkers, protein levels were inversely associated with survival, particularly with ST2 and MR-proADM, where the top versus bottom quartile was associated with an adjusted hazard ratio of 2.40 (95% CI 1.44–3.98; p = 0.001) and 2.18 (95% CI 1.35–3.51; p = 0.001), respectively, in the entire cohort, and 3.43 (95% CI 1.73–6.79; p < 0.001) and 3.49 (95% CI 1.84–6.60; p < 0.001), respectively, in extensive disease patients. A high combined score of MR-proADM and ST2 was associated with a significantly reduced median OS of 7.0 months vs. 14.9 months for patients with a low combined score. We conclude that the cardiovascular biomarkers MR-proADM and ST2 strongly correlate with survival in SCLC, warranting prospective studies on the clinical utility of MR-proADM and ST2 for improved, individualized treatment decisions.

KW - Cardiovascular biomarkers

KW - Individualized treatment

KW - Small cell lung cancer

U2 - 10.3390/cancers14051307

DO - 10.3390/cancers14051307

M3 - Article

C2 - 35267617

AN - SCOPUS:85125930369

SN - 2072-6694

VL - 14

SP - 1

EP - 14

JO - Cancers

JF - Cancers

IS - 5

M1 - 1307

ER -

Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN)

Abstract

Subject classification (UKÄ)

Free keywords

UN SDGs

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Research output

Coagulation and other aspects of the cardiovascular system in small cell lung cancer

Cite this