Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN)
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...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-03-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/5/1307 |
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| author | Emelie Gezelius Pär-Ola Bendahl Widet Gallo Kelin Gonçalves de Oliveira Lars Ek Bengt Bergman Jan Sundberg Olle Melander Mattias Belting |
| author_facet | Emelie Gezelius Pär-Ola Bendahl Widet Gallo Kelin Gonçalves de Oliveira Lars Ek Bengt Bergman Jan Sundberg Olle Melander Mattias Belting |
| author_sort | Emelie Gezelius |
| collection | DOAJ |
| description | 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-pro-atrial-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 (<i>N</i> = 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; <i>p</i> = 0.001) and 2.18 (95% CI 1.35–3.51; <i>p</i> = 0.001), respectively, in the entire cohort, and 3.43 (95% CI 1.73–6.79; <i>p</i> < 0.001) and 3.49 (95% CI 1.84–6.60; <i>p</i> < 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. |
| first_indexed | 2024-03-09T20:45:09Z |
| format | Article |
| id | doaj.art-dc84fb37ba184baa88ddaf95861aa929 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T20:45:09Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-dc84fb37ba184baa88ddaf95861aa9292023-11-23T22:49:01ZengMDPI AGCancers2072-66942022-03-01145130710.3390/cancers14051307Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN)Emelie Gezelius0Pär-Ola Bendahl1Widet Gallo2Kelin Gonçalves de Oliveira3Lars Ek4Bengt Bergman5Jan Sundberg6Olle Melander7Mattias Belting8Department of Clinical Sciences, Lund, Division of Oncology, Lund University, Barngatan 4, SE-221 85 Lund, SwedenDepartment of Clinical Sciences, Lund, Division of Oncology, Lund University, Barngatan 4, SE-221 85 Lund, SwedenClinical Research Centre, Hypertension and Cardiovascular Disease Group, Department of Clinical Sciences, Skåne University Hospital, Lund University, Jan Waldenstroms gata 35, SE-214 28 Malmo, SwedenDepartment of Clinical Sciences, Lund, Division of Oncology, Lund University, Barngatan 4, SE-221 85 Lund, SwedenDepartment of Respiratory Medicine, Lund University Hospital, Entrégatan 7, SE-221 85 Lund, SwedenDepartment of Respiratory Medicine, Sahlgrenska University Hospital, SE-413 45 Gothenburg, SwedenDepartment of Hematology, Radiophysics and Oncology, Skåne University Hospital, Lasarettsgatan 23A, SE-221 85 Lund, SwedenClinical Research Centre, Hypertension and Cardiovascular Disease Group, Department of Clinical Sciences, Skåne University Hospital, Lund University, Jan Waldenstroms gata 35, SE-214 28 Malmo, SwedenDepartment of Clinical Sciences, Lund, Division of Oncology, Lund University, Barngatan 4, SE-221 85 Lund, SwedenCardiovascular 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-pro-atrial-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 (<i>N</i> = 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; <i>p</i> = 0.001) and 2.18 (95% CI 1.35–3.51; <i>p</i> = 0.001), respectively, in the entire cohort, and 3.43 (95% CI 1.73–6.79; <i>p</i> < 0.001) and 3.49 (95% CI 1.84–6.60; <i>p</i> < 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.https://www.mdpi.com/2072-6694/14/5/1307small cell lung cancercardiovascular biomarkersindividualized treatment |
| spellingShingle | Emelie Gezelius Pär-Ola Bendahl Widet Gallo Kelin Gonçalves de Oliveira Lars Ek Bengt Bergman Jan Sundberg Olle Melander Mattias Belting Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN) Cancers small cell lung cancer cardiovascular biomarkers individualized treatment |
| title | Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN) |
| title_full | Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN) |
| title_fullStr | Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN) |
| title_full_unstemmed | Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN) |
| title_short | Circulating Levels of the Cardiovascular Biomarkers ST2 and Adrenomedullin Predict Outcome within a Randomized Phase III Lung Cancer Trial (RASTEN) |
| title_sort | circulating levels of the cardiovascular biomarkers st2 and adrenomedullin predict outcome within a randomized phase iii lung cancer trial rasten |
| topic | small cell lung cancer cardiovascular biomarkers individualized treatment |
| url | https://www.mdpi.com/2072-6694/14/5/1307 |
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