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

Gezelius, Emelie LU ; Bendahl, Pär Ola LU ; Gallo, Widet LU orcid ; de Oliveira, Kelin Gonçalves LU ; Ek, Lars LU ; Bergman, Bengt ; Sundberg, Jan ; Melander, Olle LU orcid and Belting, Mattias LU (2022) In Cancers 14(5). p.1-14
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... (More)

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.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Cardiovascular biomarkers, Individualized treatment, Small cell lung cancer
in
Cancers
volume
14
issue
5
article number
1307
pages
1 - 14
publisher
MDPI AG
external identifiers
  • pmid:35267617
  • scopus:85125930369
ISSN
2072-6694
DOI
10.3390/cancers14051307
language
English
LU publication?
yes
additional info
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.
id
b397576d-ab21-465d-8520-26a2be4de1ab
date added to LUP
2022-04-03 21:05:06
date last changed
2025-04-07 00:58:03
@article{b397576d-ab21-465d-8520-26a2be4de1ab,
  abstract     = {{<p>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 &lt; 0.001) and 3.49 (95% CI 1.84–6.60; p &lt; 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.</p>}},
  author       = {{Gezelius, Emelie and Bendahl, Pär Ola and Gallo, Widet and de Oliveira, Kelin Gonçalves and Ek, Lars and Bergman, Bengt and Sundberg, Jan and Melander, Olle and Belting, Mattias}},
  issn         = {{2072-6694}},
  keywords     = {{Cardiovascular biomarkers; Individualized treatment; Small cell lung cancer}},
  language     = {{eng}},
  number       = {{5}},
  pages        = {{1--14}},
  publisher    = {{MDPI AG}},
  series       = {{Cancers}},
  title        = {{Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN)}},
  url          = {{http://dx.doi.org/10.3390/cancers14051307}},
  doi          = {{10.3390/cancers14051307}},
  volume       = {{14}},
  year         = {{2022}},
}